Completed Studies (selected)

Studies on Multiple Sclerosis

NK Cell Study: Monitoring natural killer cells in multiple sclerosis patients treated with Fingolimod

The aim of this study is to monitor the effect of Fingolimod (Gilenya®) in the treatment of MS on natural killer (NK) cells, a subcohort of blood-derived immune cells. Although Fingolimod/Gilenya® is well established in the treatment of MS it is still not entirely clear how this drug impacts the immune system of MS patients. NK cells are crucial in the inborn immune defense. Additionally, it has recently become clear, that NK cells play an important role in the regulation of the adaptive immune system and in the pathophysiology of autoimmune diseases like MS. Therefore, better understanding of the impact of Fingolimod/Gilenya® on NK cells is important.

Participation in this clinical study is possible for both male and female patients with relapsing-remitting MS, aged 18-65, with a medical indication for treatment with Fingolimod/Gilenya®. Study duration is 12 months for every participant with 6 individual on site visits. Treatment with Fingolimod/Gilenya® will be continued after the study.

Study Director: Dr. Jan Dörr (WG Clinical Neuroimmunology, NCRC)

Course of the study: 09/2013 - 08/2018

clinicaltrials.gov

For this study no more study participants are required.

 

DENIM Study: Depression and multiple sclerosis

Depression commonly occurs in chronic illnesses. Especially patients suffering from illnesses like multiple sclerosis, which are marked by an activation of the immune system, show an increased susceptibility to developing depression. Therefore, a biological cause and effect relationship between these symptoms seem to occur. However, it is widely unknown what kind of biological mechanisms are relevant.

In this clinical study we want to gain a better understanding of the relationship between changes in the immune system and the occurrence of depression in female and male patients suffering from Multiple Sclerosis. In order to do that we are looking for female and male patients diagnosed with relapsing remitting Multiple Sclerosis with and without depression as well as healthy controls.

The study entails a one-time blood draw, a neurological examination as well as a clinical interview to determine the psychological well-being of the patient. No drugs are administered. The study examination takes about 3.5 hours (one morning). Your will receive a compensation for your participation.

Contact: Aline Tänzer aline.taenzer@charite.de

principal investigators: Prof. Dr. Friedemann Paul (working group Clinical Neuroimmunology, NCRC) and Prof. Dr. Stefan Gold (Clinic for Psychiatry, CBF)

Course of the study: 11/2015 - 06/2017

For this study no more study participants are required.

 

MS Emotion Study: Emotional processing in patients with multiple sclerosis/clinically isolated syndrome

Multiple sclerosis (MS) clinically presents with multiple neuropsychological and psychiatric symptoms which may diminish quality of life and subjective wellbeing significantly. There is controversial evidence suggesting emotional processing deficits in MS. Emotional processing (EP) can be conceptualized as the ability to adequately perceive and experience emotional salient stimuli and to use this information, for example during interpersonal communication or decision making.

The aim of this prospective non-interventional neuropsychological one visit study involving functional MRI (fMRI) is to ascertain emotional processing in patients with MS or clinically isolated syndrome (CIS) who already participate in the CIS-Study compared to healthy control subjects. The duration of the study visit is approximately two hours. Study participants will be reimboursed for time and travel.

In different experiments, the modulation of cognitive and motor responses by visual emotional information and the ability to discriminate visual emotional stimuli will be tested using experimental behavioral paradigms. Furthermore, functional connectivity and - using fMRI - activations of brain regions known to be involved with emotional processing will be evaluated.

A better understanding of the affective emotional functioning in patients with MS might contribute not only to improving patient education, -management and treatment but also potentially help identifying relevant outcome measures for the testing of clinical and subclinical effects of symptomatic or disease modifying agents in MS.

Contact: Dr. Hagen Kunte hagen.kunte@charite.de

principal investigators: Prof. Dr. Friedemann Paul (working group Clinical Neuroimmunology, NCRC) and PD Dr. Thomas Hälbig   (visiting scientist, working group Clinical Neuroimmunology, NCRC)

Course of the study: 02/2016 - 12/2016

 

EVIDIMS Study: Vitamin D in multiple sclerosis

In this study, we investigate whether the regular high-dose intake of vitamin D positively impacts the clinical course and various MRI parameters in patients with relapsing-remitting MS or even clinically isolated syndrom. A number of studies suggest that the blood level of vitamin D can influence both the disease risk and course of MS. However, it is unclear whether this also applies to the intake of vitamin D. A unique feature of this study is that, in contrast to the more frequent placebo-controlled trials, two different dosages of vitamin D are compared. This means that all study participants receive vitamin D. Participation is open to male and female patients who have received MS treatment with interferon-β1b for at least the last three months. The study drug is taken orally every two days over a period of 1.5 years and is very well tolerated. Treatment with interferon-β1b will be continued during the study. Patients will be seen and examined regularly in the study outpatient clinic.

Study Director: Dr. Jan Dörr (WG Clinical Neuroimmunology, NCRC)

Course of the study: 01/2012 - 06/2017

This study is registered in the database ClinicalTrials.gov (number NCT01440062).

Publication: Dorr, J., S. Ohlraun, H. Skarabis, and F. Paul. "Efficacy of Vitamin D Supplementation in Multiple Sclerosis (Evidims Trial): Study Protocol for a Randomized Controlled Trial." Trials 13 (Feb 08 2012): 15. http://dx.doi.org/10.1186/1745-6215-13-15. Link

MS-EPOXI: Effects of altitude training on immune function and energy metabolism in multiple sclerosis patients

In a joint study with Experimental & Clinical Research Center (ECRC) at Campus Buch, we investigate the effects of simulated altitude (2500 m above sea level) on energy metabolism and physical fitness at rest and during moderate physical activity.

We are especially interested in the effects of reduced oxygen content in the air (hypoxia) on immune function and important metabolic processes. To test this, we would ask you to spend 3 times/week each 1 h over 4 weeks in our altitude chamber, in which the oxygen concentration can be changed from 21% to 15% (comparable to the air in an aircraft). During this time, you would either only stay in the chamber or do moderate treadmill training.

Before and after this 4 week program, we would investigate your energy metabolism at rest and during moderate physical activity and assess immune functions critical for MS disease course.

Men and women with relapsing remitting MS who are ambulatory, between 20 and 60 years of age, and without any other clinically relevant comorbidity may participate.

Principle investigators: Prof. Dr. F. Paul (NCRC), Dr. M. Boschmann (ECRC)

FAM-Study: Fatigue in multiple sclerosis

A majority of patients with multiple sclerosis suffer from overwhelming tiredness, also referred to as fatigue. So far there is no effective evidence-based therapy to treat Fatigue Syndrome. The FAM-Study will investigate two non-pharmaceutical procedures – acupuncture and mindfulness training (MBSR) - for whether they are suitable therapy options for fatigue.

Patients diagnosed with multiple sclerosis suffering from fatigue for at least 3 months can take part in the trial. Participants should be aged 18 to 65 years. They must be able to walk without assistance. The therapy of multiple sclerosis and of fatigue must be stable three months before study inclusion. The trail is conducted at the NCRC in Berlin.

Study Director: Prof. Dr. med. Friedemann Paul (AG Neuroimmunologie, NCRC, ECRC)  and Prof. Dr. med. Claudia Witt (Institut für Sozialmedizin, Epidemiologie und Gesundheitsökonomie, Charite - Universitätsmedizin Berlin)

Course of the study: 04/2013 - 11/2015

This study is registered in the database ClinicalTrials.gov (number NCT01864707).

 

MOVING Study: Modification of the visual outcome after optic neuritis with Gilenya®

Many MS patients suffer from inflammation of the optic nerve at the beginning or in the course of their disorder, which often leads to a permanent damage of the nerve fibre or nerve cells. Besides its anti-inflammatory effect, the newly approved MS-treatment Gilenya® might also have a neuroprotective component. In the MOVING study we want to investigate whether an early treatment with Gilenya® might lead to a measurable reduction of neural damage compared to a standard therapy with Interferon beta.

Study duration is 6 months. Patients with relapsing-remitting MS or CIS, who recently suffered from an optic nerve inflammation can participate. Participants are seen regularly in our study outpatient clinic. Study visits include magnetic resonance imaging (MRI) and several optic examinations.

Study Director: Dr. Olaf Hoffmann (WG Clinical Neuroimmunology, NCRC) in cooperation with Prof. Dr. Friedemann Paul (WG Clinical Neuroimmunology, NCRC, ECRC)

Course of the study: 06/2013-04/2016

This study is registered in the database ClinicalTrials.gov (number NCT01647880).

 

 

REPABO Study: Patient-based measuring instruments in multiple sclerosis

Good measuring instruments are necessary to describe the benefits and harms of various therapies, whether for symptom relief or influence on the MS itself. Currently, the main standard accepted worldwide is the EDSS, the Expanded Disability Status Scale. The aim of this study is to examine patient-based investigation instruments, especially questionnaires and new objective tests, in particular a walking endurance test and eyesight check. We will examine to what extent these tools show the activity of the disease better than traditionally used instruments. Participation is open to patients with high disease activity, as well as patients without relapses and without an increase in EDSS in the last two years. Patients will be seen at the study outpatient clinic every three months for various tests and examinations.   

Study Director: Prof. Dr. Friedemann Paul (WG Clinical Neuroimmunology, NCRC, ECRC)

Laufzeit: 01/2012 - 11/2013

SUPREMES study: Sunphenon (epigallocatechin-gallate) in progressive forms of multiple sclerosis:

The SUPREMES study investigates the effectiveness of a extract gained from green tee (epigallocatechin gallat, EGCG) on various MRT parameters, disability progression and brain performance in MS patients. This is also a randomized, placebo-controlled, double-blind study. This study includes patients with primary or secondary chronic progressive MS. The running time is two and a half years per patient.

Study Director: Prof. Dr. Friedemann Paul (WG Clinical Neuroimmunology, NCRC, ECRC)

Course of the study: 11/2008-02/2016

FLORIMS Study: Flupirtine as oral treatment of MS:

In this study we are investigating whether the daily intake of Flupirtine has a positive influence on various  MRT parameters in patients with relapsing-remitting MS. Other parameters for the damaging of nerve cells, the relapse rate and the progression of disability are also determined. Flupirtine is already approved as a medicine, has an analgesic effect and presumably has neuroprotective properties. This is a multi-center, randomized, placebo-controlled, double-blind study. Participation is open to male and female patients who have been receiving MS treatment with Interferon-β1b (Betaferon®) for at least six months. The study medicine is taken as capsule twice a day for one year. The study medicine is generally tolerated well. Treatment with Interferon-β is continued during the study. In this study too, the patients are seen and examined regularly in the study outpatient clinic.

Study Director: Prof. Dr. Friedemann Paul (WG Clinical Neuroimmunology, NCRC, ECRC)

TMS-MS Study: Repetitive deep transcranial magnetic stimulation in fatigue and depressiveness in multiple sclerosis

In addition to fatigue, depressiveness is also a very frequent symptom of MS, to date it has not been possible to treat either of these symptoms well with medication. During the past few years, so-called transcranial magnetic stimulation (TMS) has increasingly been used successfully for the treatment of depression. We examine the effect of a new kind of TMS method upon depression and fatigue in patients with MS. This study is oriented towards MS patients with fatigue syndrome and/or depression and is open for all forms of MS.

Study Director: Prof. Dr. Friedemann Paul (WG Clinical Neuroimmunology, NCRC, ECRC)

Laufzeit der Studie: 02/2010 - 12/2011

Publications:

Gaede, G., M. Tiede, I. Lorenz, A. U. Brandt, C. Pfueller, J. Dorr, J. Bellmann-Strobl, S. K. Piper, Y. Roth, A. Zangen, S. Schippling, and F. Paul. "Safety and Preliminary Efficacy of Deep Transcranial Magnetic Stimulation in Ms-Related Fatigue." Neurol Neuroimmunol Neuroinflamm 5, no. 1 (Jan 2018): e423. Link

 

TRIOMS Study: Treatment of multiple sclerosis with pig whipworm eggs

Recent data suggest that an asymptomatic worm infection by the pig whipworm can reduce disease activity of autoimmune disorders. We want to investigate this approach in the TRIOMS study in patients with relapsing-remitting MS or Clinically Isolated syndrome (CIS). One group of study participants will regularly take in a liquid containing purified pig whipworm eggs for one year. The other group will receive an identically appearing placebo liquid. Efficacy will for the main part be measured by magnetic resonance imaging (MRI). Previous data suggest a very good tolerability of the eggs.

Patients with relapsing-remitting MS or CIS, who do not tolerate standard treatments with interferons or glatirameracetate, or in which these are not effective can participate in this study. Participants are seen regularly in our study outpatient clinic.

Study Director: Dr. Berit Rosche (Departement of Neurology) in cooperation with Prof. Dr. Friedemann Paul (WG Clinical Neuroimmunology, NCRC, ECRC)

Course of the study: 09/2012-03/2016

This study is registered in the database ClinicalTrials.gov (number NCT01413243).

 

SLOAN Study: Investigation of the suitability of low-contrast SLOAN eye charts as a method for the evaluation of disease progression in multiple sclerosis

This study is a progression investigation into contrast visual acuity, which is often impaired with MS. In this study, three visits take place in two years and these include neurological examination, optical coherence tomography and SLOAN contrast charts. This study is open to patients with clinically isolated syndrome, relapsing-remitting and secondary progressive MS.

Study Director: Dr. Jan Dörr (WG Clinical Neuroimmunology, NCRC)

FLIMMERBOX Study: Investigation of critical flicker frequency as a functional parameter of retinal function in patients with multiple sclerosis

This is a follow-up study involving the critical flicker frequency (CFF). CFF is the repetition frequency of a blinking light signal at which the temporal resolution ability of the eye can distinguish individual light signals. In other words, the CFF describes the frequency at which a person no longer perceives continuous light but rather a flickering signal. In this research project we investigate whether the CFF in MS patients differs from that of healthy individuals, and also whether the CFF in MS patients correlates with measurable damage to nerve fibers. There will be three visits during this 1.5-year study, including a neurological examination, optical coherence tomography and an examination of the CFF. This study is open to patients with relapsing-remitting MS.

Study Director: Dr. Jan Dörr (WG Clinical Neuroimmunology, NCRC)

Laufzeit der Studie: 10/2011-01/2016

VISION Study: Visual restitution therapy after optic neuritis

In this study, we investigate whether the so-called visual restitution therapy (daily 30-minute domestic exercising of the sick eye with a PC-based program) improves vision after optic neuritis (inflammation of the optic nerve). Participation is open to all sufferers who have had acute optic neuritis in the last 6 months before inclusion or still have impaired vision from optic neuritis further in the past. This study is open to all forms of MS.

Study Director: Prof. Dr. Friedemann Paul (WG Clinical Neuroimmunology, NCRC, ECRC)

Studies on Stroke

GUTSTROKE – Influence of stroke on the composition of intestinal microbiota

The intestinal flora (intestinal microbiota) creates a microbial metabolic organ comprised of 1013 to 1014 microorganisms, with a genome (microbiome) 100 times larger than the human one. The metabolic capacity of intestinal microbiota is comparable to the human liver. Recently, a bidirectional communication axis between brain and the gut microbiota was described and suggested to be an important player in the development and course of several diseases of the nervous system. Changes in the composition of gut microbiota were associated with e.g. autism, depressions, Guillain-Barré syndrome and multiple sclerosis. Additionally, in the last years a link between disturbances of the microbiota composition, atherosclerosis and an increased risk for cardiovascular events was described.

In this study we aim to examine whether the composition of intestinal microbiota changes after stroke and whether the intestinal microbiome of severely affected stroke patients differs from patients with only transient ischemic episodes in the brain (transient ischemic attack, TIA). In addition, we plan to study the immunological parameters in enrolled patients and to assess whether any stroke-associated changes in the gut microbiota are linked to changes in the immune response.

This is a proof of concept, prospective, observational study.

Study Director: Prof. Dr. Andreas Meisel (WG Cerebrovascular Diseases, NCRC, CSB, Neurology CCM)

clinicaltrials.gov

 

Physical fitness in subacute stroke (PHYS-Stroke)

Given the rising number of strokes worldwide, and the large number of individuals left with disabilities after stroke, novel strategies to reduce disability, increase functions in the motor and the cognitive domains, and improve quality of life are of major importance. Physical activity is a promising intervention to address these challenges but, as yet, there is no study demonstrating definite outcomes. Our objective is to assess whether additional treatment in the form of physical fitness-based training for patients early after stroke will provide benefits in terms of functional outcomes, in particular gait speed and the Barthel Index (co-primary outcome measures) reflecting activities of daily living (ADL). We will gather secondary functional outcomes as well as mechanistic parameters in an exploratory approach. The ultimate goal of this endpoint-blinded, phase III randomised controlled trial is to provide evidence to guide post-stroke physical fitness-based rehabilitation programmes, and to elucidate the mechanisms underlying this intervention.

Study director: Prof. Dr. med. Agnes Flöel (WG Cognitive Neurology, NCRC, Neurology CCM)

 

Managing Aftercare for Stroke (MAS): MAS-II - A longitudinal, complex, interventional study in post-rehabilitation stroke patients

After discharge from hospital the current healthcare system in Germany allows considerable flexibility (therefore complexity) of patient access and mobility between multiple care providers in the community setting. We believe this aftercare could be better coordinated by a specialized coordinated stroke aftercare service. Comprehensive coordinated multidisciplinary care is a proven concept with proven benefits in both acute and rehabilitation care provided in stroke units and neurorehabilitation centres. In MAS approach we postulate that a similar coordinated approach to care can be extended to the phase after in-patient rehabilitation has ended (i.e. “long-term management” as opposed to “early supported discharge”) for disabled patients with stroke living in the community. In this second step of the MAS project we will assess the feasibility of integrated post-stroke care and estimate it’s effect size on quality of life (phase MAS-II). The ultimate aim of the complete MAS project (MAS I, II & III) is the development of a model of stroke aftercare delivery that can be evaluated to estimate effects in both our local and the wider stroke population.

Study Director: Prof. Dr. Andreas Meisel (WG Cerebrovascular Diseases, NCRC, CSB, Neurology CCM)

Contact: Dr. Benjamin Hotter benjamin.hotter@charite.de

Publikation: Hotter, Benjamin, Inken Padberg, Andrea Liebenau, Petra Knispel, Sabine Heel, Diethard Steube, Jörg Wissel, Ian Wellwood, and Andreas Meisel. "Identifying Unmet Needs in Long-Term Stroke Care Using in-Depth Assessment and the Post-Stroke Checklist – the Managing Aftercare for Stroke (Mas-I) Study." European Stroke Journal 0, no. 0 (2396987318771174. Link

Link zur Studie bei clinicaltrials.gov

Flyer

 

ARIMIS Study: Autoimmune phenomena after a stroke

Stroke leads in the short-term to a substantial reduction in the functional ability of the immune system (stroke-induced immunodeficiency - CIDS). This encourages the occurrence of infections (e.g. pneumonia). On the other hand, the destruction of the brain tissue by the stroke can also favor the arising of autoimmune mechanisms. In such a case, the immune system attacks the body's own tissues. In this study, we want to show whether the stroke leads to the arising of autoimmune mechanisms and what influence these have upon the clinical course of the disease after the stroke. In the framework of this study, blood is taken from patients who have suffered a moderately severe to severe stroke, directly after inclusion in this study within 36 hours, after three, seven, 90 and 180 days after the stroke and tested for immunological changes. In addition, thorough clinical examinations are carried out.

Study Director: Dr. Juliane Klehmet (WG Cerebrovascular Diseases, NCRC, Neurology CCM)

Publication: Klehmet, J., S. Hoffmann, G. Walter, C. Meisel, and A. Meisel. "Stroke Induces Specific Alteration of T Memory Compartment Controlling Auto-Reactive Cns Antigen-Specific T Cell Responses." J Neurol Sci 368 (Sep 15 2016): 77-83. http://dx.doi.org/10.1016/j.jns.2016.06.039. Link

 

Brain Stimulation Studies: Brain stimulation and intensive training in the rehabilitation of chronic motor paresis and chronic aphasia following stroke

In these projects, patients who have suffered paralysis (motor paresis) or a language disorder (aphasia) following stroke are examined through intensive physiotherapeutic training as well as a combination of physiotherapeutic training and transcranial direct current stimulation or through highly intensive individually customized naming training as well as a combination of intensive naming training and transcranial direct current stimulation. At the same time, the underlying mechanisms will be recorded through structural and functional imaging techniques (as well as single-pulse transcranial magnet stimulation).

Study Director: Prof. Dr. Agnes Flöel (WG Cognitive Neurology, NCRC, CSB, Neurology CCM)

Link to study CATS at clinicaltrials.gov

Course of the study: 05/2012 - 02/2015

Publication:

Breitenstein, C., T. Grewe, A. Floel, W. Ziegler, L. Springer, P. Martus, W. Huber, K. Willmes, E. B. Ringelstein, K. G. Haeusler, S. Abel, R. Glindemann, F. Domahs, F. Regenbrecht, K. J. Schlenck, M. Thomas, H. Obrig, E. de Langen, R. Rocker, F. Wigbers, C. Ruhmkorf, I. Hempen, J. List, A. Baumgaertner, and Fcet Ec study group. "Intensive Speech and Language Therapy in Patients with Chronic Aphasia after Stroke: A Randomised, Open-Label, Blinded-Endpoint, Controlled Trial in a Health-Care Setting." Lancet 389, no. 10078 (Apr 15 2017): 1528-38. http://dx.doi.org/10.1016/S0140-6736(17)30067-3. Link

KMS-1 Study: Use of a circle monitor system for diagnosing symptoms of neglect

Neglect is a common syndrome after a stroke. Patients with neglect no longer perceive stimuli which are spatially contra lateral to the damaged hemisphere of the brain. In daily life this leads to serious limitations. Moreover, the occurrence of neglect is a negative predictor for expected patient recovery.

Currently, in addition to observing spontaneous behaviour, cross-out tasks ("paper and pencil" tests) are the main means of diagnosing neglect. The downside of these tasks is that they only test a small spatial area. In this study, new possibilities for diagnosing neglect will be tested on a circle monitor. This system consists of touch screens on which tasks can be presented and solved. We hope that testing with this system will increase diagnostic accuracy since it addresses a much larger search field.

The aim of this study is to detect even mild symptoms which are not picked up by traditional tests but can be relevant in complex daily life situations. This would make goal-oriented treatment possible for affected patients. In the long term, we also want to use this technology to improve therapy for neglect patients by modeling tasks from everyday life.

Study Director: Prof. Dr. Andreas Meisel (WG Cerebrovascular Diseases, NCRC, CSB, Neurology CCM)

Contact person: Dr. Lena Ulm (WG Cerebrovascular Diseases, NCRC, Neurology CCM)

Participating cooperation partners: NeuroCure Cluster of Excellence (Prof. York Winter), Median Klinik Berlin-Kladow (Dr. Christian Dohle), Freie Universität Berlin, Department of Experimental Psychology and Neuropsychology (Prof. Michael Niedeggen), Berlin Center for Advanced Neuroimaging BCAN, and the graduate school Berlin School of Mind and Brain (Dr. Daniel S. Margulies).

Publication: Ulm, L., D. Wohlrapp, M. Meinzer, R. Steinicke, A. Schatz, P. Denzler, J. Klehmet, C. Dohle, M. Niedeggen, A. Meisel, and Y. Winter. "A Circle-Monitor for Computerised Assessment of Visual Neglect in Peripersonal Space." PLoS One 8, no. 12 (2013): e82892. http://dx.doi.org/10.1371/journal.pone.0082892. Link

 

KMS-2 Study: Diagnostics of induced neglect symptomatology by means ot the encircling-monitor-system

Neglect is a common syndrome after a stroke. Patients with neglect no longer perceive stimuli which are spatially contra lateral to the damaged hemisphere of the brain. In daily life this leads to serious limitations. Moreover, the occurrence of neglect is a negative predictor for expected patient recovery.

Currently, in addition to observing spontaneous behaviour, cross-out tasks (“paper and pencil” tests) are the main means of diagnosing neglect. The downside of these tasks is that they only test a small spatial area. In the first phase of the project (KMS-1 pilot study), we could increase diagnostic accuracy with an encircling-monitor-system which consists of touch screens on which tasks can be presented and solved. We could detect even mild symptoms which are not picked up by traditional tests but can be relevant in complex daily life situations. This makes goal-oriented treatment possible for affected patients. In the long term, we also want to use this technology to improve therapy for neglect patients by modelling tasks from everyday life.  

Based on our study KMS-1 we now want to test healthy participants, after inducing short-term neglect symptoms by means of non-invasive brain stimulation (tDCS). Contrarily to other stroke caused impairments like speech disorders or visual field defects, it is yet insufficiently examined which lesion locations are responsible for the different manifestations of neglect. The reason is that patients with neglect usually have widely spread lesions which have impaired many areas of the brain.  tDCS gives the opportunity to stimulate specific brain regions and to examine their selective impact on the neglect symptoms. tDCS is without risk and does not lead to any negative sensations or permanent cognitive or sensory restrictions. A selective examination of the underlying mechanisms and involved structure-function-correlations in neglect would help to understand this syndrome and could positively affect the diagnostics and therapy and therefore chances of rehabilitation of these patients.

Study Director: Prof. Dr. Andreas Meisel (WG Cerebrovascular Diseases, NCRC, CSB, Neurology CCM)

Contact persons: Dr. Lena Ulm, Dorota Wohlrapp (MS) (WG Cerebrovascular Diseases, NCRC, Neurology CCM)

Participating cooperation partners: NeuroCure Cluster of Excellence (Prof. Dr. Agnes Flöel , Prof. York Winter), Median Klinik Berlin-Kladow (Dr. Christian Dohle), Freie Universität Berlin, Department of Experimental Psychology and Neuropsychology (Prof. Michael Niedeggen), Berlin Center for Advanced Neuroimaging BCAN, and the graduate school Berlin School of Mind and Brain (Dr. Daniel S. Margulies).

PREDICT Study: Prediction of stroke-associated pneumonias

PREDICT is an observation study on the predictive power of clinical parameters and bio-markers regarding stroke-associated pneumonia. This is intended to allow targeted prevention of this life-threatening complication in stroke patients. You can find more detailed information here

Study Director: Prof. Dr. Andreas Meisel (WG Cerebrovascular Diseases, NCRC, CSB, Neurology CCM)

Course of the study: 02/2010-04/2013

This study is registered in the database ClinicalTrials.gov (number NCT01079728).

Publication: Hoffmann, S., H. Harms, L. Ulm, D. G. Nabavi, B. M. Mackert, I. Schmehl, G. J. Jungehulsing, J. Montaner, A. Bustamante, M. Hermans, F. Hamilton, J. Gohler, U. Malzahn, C. Malsch, P. U. Heuschmann, C. Meisel, A. Meisel, and Predict Investigators. "Stroke-Induced Immunodepression and Dysphagia Independently Predict Stroke-Associated Pneumonia - the Predict Study." J Cereb Blood Flow Metab (Jan 01 2016): 271678X16671964. http://dx.doi.org/10.1177/0271678X16671964. Link

 

STRAWINSKI Study: An unfavorable outcome after a stroke is associated with nosocomial infections: PCTus-based antibacterial therapy in patients with severe ischemic stroke

The development of stroke-associated infections has a negative influence on the outcome, i.e. the course of the disease after the stroke. The early identification of high-risk patients, made possible by biomarkers, could lead to an improvement of outcomes after a stroke due to the early starting of antibiotic therapy. With this study, we would like to investigate whether intensive infection monitoring by means of Procalcitonin ultrasensitive (PCTus) not only permits early and targeted treatment with antibiotics, but can also improve the functional outcome after a stroke - in comparison with a standard therapy based on the current guidelines.

This is a multicenter, randomized, double-blind study.

Study Director: Prof. Dr. Andreas Meisel (WG Cerebrovascular Diseases, NCRC, CSB, Neurology CCM)

Course of the study:12/2010-2014

This study is registered in the database ClinicalTrials.gov (number NCT01264549)

Publication: Ulm, L., S. Ohlraun, H. Harms, S. Hoffmann, J. Klehmet, S. Ebmeyer, O. Hartmann, C. Meisel, S. D. Anker, and A. Meisel. "Stroke Adverse Outcome Is Associated with Nosocomial Infections (Strawinski): Procalcitonin Ultrasensitive-Guided Antibacterial Therapy in Severe Ischaemic Stroke Patients - Rationale and Protocol for a Randomized Controlled Trial." Int J Stroke 8, no. 7 (Oct 2013): 598-603. http://dx.doi.org/10.1111/j.1747-4949.2012.00858.x. Link

Hotter, B., K. Jegzentis, J. Steinbrink, W. U. Schmidt, M. Endres, A. Meisel, W. Haverkamp, and G. J. Jungehulsing. "Impact of Selection Criteria on Recruitment in an Interventional Stroke Trial." Cerebrovasc Dis 36, no. 5-6 (2013): 344-50. Link

Ulm, L., S. Hoffmann, D. Nabavi, M. Hermans, B. M. Mackert, F. Hamilton, I. Schmehl, G. J. Jungehuelsing, J. Montaner, A. Bustamante, M. Katan, A. Hartmann, S. Ebmeyer, C. Dinter, J. C. Wiemer, S. Hertel, C. Meisel, S. D. Anker, and A. Meisel. "The Randomized Controlled Strawinski Trial: Procalcitonin-Guided Antibiotic Therapy after Stroke." Front Neurol 8 (2017): 153. Link

 

Studies on Myasthenia Gravis

The role of the thymus in myasthenia gravis

Although the association between expansion or a tumor of the thymus and autoimmune myasthenia gravis has already been known for a long time, the cause and effect of this link continues to be unexplained. With this study, we are hoping for new findings on the occurrence of myasthenia and the autoantibody formation associated with it. Moreover, we would like to investigate the effects of a removal of the thymus upon the immune system in the context of myasthenia gravis. For this purpose, we are examining myasthenia patients with and without thymus tumor and thymus tumor patients without myasthenia before and after operative removal of the thymus gland.

Study Director: Dr. Siegfried Kohler (AG Cerebrovascular Diseases, NCRC, Neurology CCM)

Course of the Study: 07/2008-12/2012

 

Studies on Chronic Inflammatory Demyelinating Polyneuropathy CIDP

Mechanisms of immune regulation by IVIG

This study investigates the effect of immunoglobulins (antibodies) on cellular components of the immune system. We are above all interested to what extent the administering of immunoglobulins changes the function of certain immune cells.

Study Director: Dr. Hendrik Harms (WG Cerebrovascular Diseases, NCRC, Neurology CCM)

Publikationen:

Klehmet, J., J. Goehler, L. Ulm, S. Kohler, C. Meisel, A. Meisel, and H. Harms. "Effective Treatment with Intravenous Immunoglobulins Reduces Autoreactive T-Cell Response in Patients with Cidp." J Neurol Neurosurg Psychiatry 86, no. 6 (Jun 2015): 686-91. http://dx.doi.org/10.1136/jnnp-2014-307708. Link

Klehmet, J., M. Staudt, L. Ulm, N. Unterwalder, A. Meisel, and C. Meisel. "Circulating Lymphocyte and T Memory Subsets in Glucocorticosteroid Versus Ivig Treated Patients with Cidp." J Neuroimmunol 283 (Jun 15 2015): 17-22. http://dx.doi.org/10.1016/j.jneuroim.2015.03.023. Link

 

Studies on Developmental Disorders of the Nervous System (e.g. Epilepsy)

CARDIF Study: Carbon dioxide in the treatment of febrile seizures

5% of all children suffer from at least one febrile seizure once in their lifetime. 30% of these children have recurrent or particularly long-lasting febrile seizures which is very incriminating for affected parents. The current standard therapy consists in the rectal administration of diazepam in cases where the seizure lasts longer than 3 minutes. Unfortunately, this substance is not always effective. Furthermore, it has a sedating effect, i.e. after administration the children usually sleep for the rest of the day or are dazed. 

Previous work showed that the inhalation of an increased carbon dioxide concentration could stop febrile seizures quickly. We now want to confirm these findings in a bigger randomized, placebo-controlled, double-blind study using carbogen (containing 5% carbon dioxide and 95% oxygen). All previous data show a very high safety of carbogen. Carbogen will be administered via a low pressure can (similar to a spray can). Participating patients will receive these cans for the use at home.

Study Director: Prof. Dr. Markus Schülke-Gerstenfeld (WG Developmental Disorders of the Nervous System, NCRC, Pediatrics CVK)

Course of the study: 2012-06/2015

This study is registered in the database ClinicalTrials.gov (number NCT01370044).

Publication: Ohlraun, S., T. Wollersheim, C. Weiss, P. Martus, S. Weber-Carstens, D. Schmitz, and M. Schuelke. "Carbon Dioxide for the Treatment of Febrile Seizures: Rationale, Feasibility, and Design of the Cardif-Study." J Transl Med 11 (Jun 27 2013): 157. http://dx.doi.org/10.1186/1479-5876-11-157. Link

 

 

Studies on Mild Cognitive Impairment (MCI) and Alzheimer's Disease

Lifestyle Studies: The impact of lifestyle factors on the brain

Previous findings suggest that a healthy lifestyle can help reduce the risk of age-related diseases. In addition to smoking, alcohol consumption, weight and social interaction, special importance has been attributed to physical activity and nutrition. The direct impact of these influences on human cognition is, however, unclear, as are the underlying mechanisms.

This group investigates in various intervention studies (Project 1: Improving the brain through diet in elderly individuals; Project 2: Improving the brain through a combination of diet, exercise and cognitive stimulation in elderly individuals with existing Mild Cognitive Impairment MCI) the impact of exercise and healthy eating habits (including calorie restriction and omega-3 fatty acids) on the aging brain. To do this, neuropsychological tests, analysis of peripheral biomarkers in the blood, and imaging techniques such as structural and functional magnetic resonance imaging (MRI) will be used.

Study Director: Prof. Dr. Agnes Flöel (WG Cognitive Neurology, NCRC, CSB, Neurology CCM)

Course of the study (Project 2): 07/2013-05/2014

Publication: Bohlken, J., T. Kobe, L. M. Dietz, M. A. Rapp, T. Kohlmann, and A. Floel. "[Differences in Attitudes of Patients with Mild Cognitive Impairment Towards Early Diagnosis at a University Clinic and a Specialist Physician's Office]." Fortschr Neurol Psychiatr 83, no. 10 (Oct 2015): 563-7. http://dx.doi.org/10.1055/s-0041-108097.  Link

 

SUNAK Study: Sunphenon EGCg (Epigallocatechin Gallate) in the early stage of Alzheimer's disease

In this study, we investigate whether the regular taking of the extract of green tea (epigallocatechin gallate, EGCG) can slow the progression of the disease in patients with Alzheimer's disease. This is a multi-center, randomized, placebo-controlled, double-blind study. Participation is open to male and female patients, from the age of 60, who have been diagnosed with Alzheimer's type dementia, who are in an early phase of the disease. The study medicine is taken twice a day as a capsule.

Study Director: Prof. Dr. Friedemann Paul (WG Clinical Neuroimmunology, NCRC, ECRC)

Course of the study: 10/2009-2015

This study is registered in the database ClinicalTrials.gov (number NCT00951834).

 

LESO study: Mechanism of tDCS-induced learning enhancement – the role of serotonin

Transcranial direct current stimulation (tDCS) can enhance learning and memory performance (e.g., during the treatment of patients with amnestic mild cognitive impairments). This non-invasive brain stimulation technique increases cortical excitability and significantly improves performance learning and memory performance (Flöel et al., 2008). Improvements, however, were small and of short duration. Nitsche et al. (2009), however, demonstrated that a selective serotonin reuptake inhibitor (SSRI) enlarges the neuroplastic excitability enhancement accomplished by tDCS over the motorcortex. The current study, therefore, investigates whether an SSRI (Citalopram) also enhances and prolongs tDCS-induced neuroplasticity during an object-location learning task in young and older healthy subjects.

Study director: Prof. Dr. Agnes Flöel (WG Cognitive Neurology, NCRC, Neurology CCM)

Course of the study: 04/ 2014- 12/2014

This study is registered in the database ClinicalTrials.gov (number NCT02092974).

Publication: Prehn, K., H. Stengl, U. Grittner, R. Kosiolek, A. Olschlager, A. Weidemann, and A. Floel. "Effects of Anodal Transcranial Direct Current Stimulation and Serotonergic Enhancement on Memory Performance in Young and Older Adults." Neuropsychopharmacology 42, no. 2 (Jan 2017): 551-61. http://dx.doi.org/10.1038/npp.2016.170. Link

 

Transcranial direct current stimulation and intensive cognitive training in patients with mild cognitive impairment

The aim of the project is to study the efficacy and the underlying mechanisms of a new approach in the treatment of patients with (amnestic) mild cognitive impairments. The treatment combines an intensive training of a visual-spatial task lasting several days and simultaneous brain stimulation. Structural and functional cerebral correlates of behavioral changes were measured using magnetic resonance tomography (MRT).

Study director: Prof. Dr. med. Agnes Flöel (WG Cognitive Neurology, NCRC, Neurology CCM)

ClinicalTrials.gov

 

Enhancement of gestural-verbal semantic integration in young adults using non-invasive brain stimulation

Understanding actions based on either language or observation of gestures is presumed to involve the motor system, and reflect the engagement of an embodied conceptual network. The aim of the project is to test whether there is a possibility to enhance the interaction between words and gestures thus, improving their integration. Therefore, over a pre-defined brain region (left sensorimotor cortex; M1) non-invasive brain stimulation is applied during task performance. In order to evaluate specific effects on gestural-verbal integration performance on control tasks will be assessed as well.

PI: Prof. Dr. med. Agnes Flöel (Section Cognitive Neurology, NCRC, Neurologie CCM)

Project Partner: Prof. Lavidor Michal, Bar Ilan University, Israel

Supported by a Grant from the German-Israeli Foundation for Scientific Research and Development (GIF)

 

Impact of non-invasive brain stimulation during sleep on memory consolidation

The beneficial effect of sleep on memory consolidation is well documented in young, healthy adults. Recent evidence in young healthy subjects additionally suggests that sleep-associated consolidation can be amplified by the application of weak transcranial oscillatory electric currents. However, it is unknown if this effect can also be induced in healthy older adults and patients with neurodegenerative diseases (e.g., Morbus Alzheimer, patients with mild cognitive impairments (MCI)), populations known to suffer from both disturbances in sleep architecture and memory consolidation.

In this project we will assess if older adults and patients with MCI also benefit from transcranial slow oscillatory stimulation applied during periods of nocturnal as well as daytime sleep.

Cooperation partner: Department of Experimental and Neurocognitive Psychology,  Freie Universität Berlin (Dr. Sascha Tamm) 

Study director: Prof. Dr. med. Agnes Flöel (WG Cognitive Neurology, NCRC, Neurology CCM)

ClinicalTrials.gov

Publications:

Ladenbauer, J., N. Kulzow, S. Passmann, D. Antonenko, U. Grittner, S. Tamm, and A. Floel. "Brain Stimulation During an Afternoon Nap Boosts Slow Oscillatory Activity and Memory Consolidation in Older Adults." Neuroimage 142 (Nov 15 2016): 311-23. http://dx.doi.org/10.1016/j.neuroimage.2016.06.057. Link

Ladenbauer, J., J. Ladenbauer, N. Kulzow, R. de Boor, E. Avramova, U. Grittner, and A. Floel. "Promoting Sleep Oscillations and Their Functional Coupling by Transcranial Stimulation Enhances Memory Consolidation in Mild Cognitive Impairment." J Neurosci 37, no. 30 (Jul 26 2017): 7111-24. http://dx.doi.org/10.1523/JNEUROSCI.0260-17.2017. Link

Ladenbauer, J., N. Kulzow, S. Passmann, D. Antonenko, U. Grittner, S. Tamm, and A. Floel. "Brain Stimulation During an Afternoon Nap Boosts Slow Oscillatory Activity and Memory Consolidation in Older Adults." Neuroimage 142 (Nov 15 2016): 311-23. http://dx.doi.org/10.1016/j.neuroimage.2016.06.057. Link

TRAINSTIM: Improvement of memory functions in older adults by training and non-invasive brain stimulation

This project aims at the investigation of neuronal correlates and underlying mechanisms of non-invasive electrical stimulation in older adults of work and retirement age. Furthermore stimulation-induced effects on episodic memory functions will be examined as well as the difference of these effect between age groups and compared to a young control group. We use in-vivo magnetic resonance (MR) spectroscopy and well as functional and structural connectivity assessments in order to probe associated neuronal correlates.

On the basis of the results, we will develop a new training paradigm for working and episodic memory in order to examine the efficiency of a combined approach (computer-based training during stimulation) in a home-based context. The aim is to induce long-lasting effects not only on trained by also other tasks as well as activities of daily living.

Study director: Prof. Dr. med. Agnes Flöel (WG Cognitive Neurology, NCRC, Neurology CCM)

 

Publications:

Antonenko, D., M. Faxel, U. Grittner, M. Lavidor, and A. Floel. "Effects of Transcranial Alternating Current Stimulation on Cognitive Functions in Healthy Young and Older Adults." Neural Plast 2016 (2016): 4274127. http://dx.doi.org/10.1155/2016/4274127. Link

Antonenko, D., F. Schubert, F. Bohm, B. Ittermann, S. Aydin, D. Hayek, U. Grittner, and A. Floel. "Tdcs-Induced Modulation of Gaba Levels and Resting-State Functional Connectivity in Older Adults." J Neurosci 37, no. 15 (Apr 12 2017): 4065-73. http://dx.doi.org/10.1523/JNEUROSCI.0079-17.2017. Link

Cognitive impairment after repeated concussions

Mild traumatic brain injury (mTBI) occurs frequently, especially in risk sports like soccer, American football or ice hockey. A number of studies have shown that mTBI can lead to permanent cognitive deficits. Furthermore, subjects who had mTBI in earlier life, are more prone to develop dementia in older age. Interestingly, patients after mTBI show advanced neurodegeneration in middle to older age. The exact pathomechanisms are yet unclear, although changes in neurotransmitter activity, especially GABA-activity, are being discussed.

PROJECT 1: To investigate the influence of anodal transcranial direct current stimulation (tDCS) on GABA-activity in young patients (< 40 years), who suffered repeated grade 1 mTBI. Neurotransmitter activity is determined by using non-invasive brain stimulation techniques (transcranial magnetic stimulation, TMS). Patients will receive a detailed neuropsychological testing and MRI of the head. Perspectively, tDCS may be a tool to restore GABA-activity in the brain, which may in turn help to prevent cognitive deterioration in these patients before obvious cognitive deficits occur.

PROJECT 2: To examine the influence of anodal transcranial direct current stimulation (tDCS) on GABA-activity in older patients (> 55 years) who have suffered grade 1 mTBI before the age of 35. The neurotransmitter activity is determined using TMS as in Project 1. Patients will receive an MRI and a detailed neuropsychological testing. In addition, different biomarkers of cerebral inflammation are determined. Follow-up examinations (TMS, MRI, blood samples) after one and two years will show, whether neurotransmitter acitivity or blood biomarkers are predictors of accelerated neurodegeneration.

Study director: Prof. Dr. Agnes Flöel (WG Cognitive Neurology, NCRC, Neurology CCM)

ClinicalTrials.gov

 

Studies on Glucose Tolerance (a selection):

Glucose tolerance study: Training – beneficial for vessels and nerve cells?

Previous findings suggest that exercise has a positive effect on vessels supplying the brain. Moreover, it has been shown that exercise can improve existing conditions of impaired glucose tolerance or diabetes mellitus, even in the absence of accompanying weight loss.

In this mono-center, prospective, single blind, randomized, placebo-controlled study, the effects of “Nordic Walking” on memory capacity and vascular functions in elderly people will be investigated. Our results will make it possible to develop specific exercise interventions for this group of elderly individuals, and possibly even pharmaceutical “exercise mimetics” (e.g. neurotrophic factors that can be injected).

Study Director: Prof. Dr. Agnes Flöel (WG Cognitive Neurology, NCRC, CSB, Neurology CCM)

Course of the study: 01/2011 - 01/2015

This study is registered in the database ClinicalTrials.gov (number NCT01219231).

Publication:

Prehn, K., A. Lesemann, G. Krey, A. V. Witte, T. Kobe, U. Grittner, and A. Floel. "Using Resting-State Fmri to Assess the Effect of Aerobic Exercise on Functional Connectivity of the Dlpfc in Older Overweight Adults." Brain Cogn (Aug 23 2017). http://dx.doi.org/10.1016/j.bandc.2017.08.006. Link

Studies on Duchenne Muscular Dystrophy:

SUNIMUD Study: Sunphenon EGCg (epigallocatechin gallate) in Duchenne type muscular dystrophy

In this study, which is being carried out in close cooperation with the Social Pediatric Center (SPZ) for Neuropediatrics at the Charité-Campus Virchow Klinikum (CVK) and the Clinic for Child and Adolescent Medicine of the DRK Kliniken Berlin Westend, we are investigating whether the regular taking of the extract of green tea (epigallocatechin gallate, EGCG) positively influences the progression of disability of patients with Duchenne muscular dystrophy. This is a multi-center, randomized, placebo-controlled, double-blind study. Participation is open to male patients from the age of five who have been diagnosed with Duchenne muscular dystrophy. The study medicine is taken twice a day as a capsule.

Study Director: Prof. Dr. Friedemann Paul (WG Clinical Neuroimmunology, NCRC, ECRC), Dr. Ulrike Grieben (SPZ, Pediatrics)

ClinicalTrials.gov

For this study no more study participants are required.