PREPARE: Prevention of Paclitaxel-Related neurological side effects with Lithium - A Randomized, Double-Blind, Placebo-Controlled, Exploratory Proof-of-Concept Phase II Clinical Trial for the Preventi

Study Description:
Neurological side effects are among the most common complications of chemotherapy with (nab-) paclitaxel. Chemotherapy-induced polyneuropathy (CIPN) is a potentially irreversible side effect and one of the most common reasons for dose adjustment or early termination of chemotherapy. CIPN manifests itself clinically as (painful) sensory paresthesia and numbness in the hands and feet, as well as fine motor skills and/or gait disturbance. Some tumor patients also report cognitive dysfunction such as impaired concentration and memory due to chemotherapy (PCCI). So far, there is no causal treatment to prevent neurological sequelae caused by chemotherapy.

Building on extensive preliminary work, we aim to investigate in a multicenter randomized exploratory double-blind placebo-controlled trial whether co-medication with lithium carbonate can prevent or attenuate CIPN and PCCI in breast cancer patients receiving (nab-) paclitaxel chemotherapy. Patients in the intervention group will receive extended-release lithium tablets adjusted to serum lithium levels for the duration of (nab-) paclitaxel treatment, and patients in the control group will receive placebo. The safety of the study medication is ensured by close monitoring. The aim of the study is to show that patients treated with lithium carbonate develop fewer and less severe CIPN and that treatment with lithium carbonate is safe and well tolerated.

Contacts: 
PD Dr. med. Petra Hühnchen (petra.huehnchen(at)charite.de)
PD Dr. med. Wolfgang Böhmerle (wolfgang.boehmerle(at)charite.de)

Principle Investigator:
Prof. Dr. med. Matthias Endres (Director, Clinic for Neurology)
Prof. Dr. med. Jens-Uwe Blohmer (Director, Clinic for Gynecology and Breast Center)

Study Coordination:
PD Dr. med. Petra Hühnchen, PD Dr. med. Wolfgang Böhmerle

Projekt Management:
Prof. Dr. med. Matthias Endres (Director, Clinic for Neurology)

Registration:
The study is registered in DRKS (DRKS00027165)

Course of the study:
01.04.2022 - 31.03.2025

Projekt partners:
Carl-Thiem-Klinikum Cottbus, Breast Center and Systemic Gynecology
University Hospital Essen, Clinic for Neurology
Greifswald University Medical Center, Clinic for Neurology
University Hospital Carl Gustav Carus Dresden, Clinic for Neurology
Hanover Medical School, Clinic for Neurology
University Hospital Giessen, Clinic for Gynecology
Mamma Center Hamburg

Funding:
Berlin Institute of Health (BIH)
Bundesministerium für Bildung und Forschung (BMBF)

Publications:
Schlecker C, Boehmerle W, Jeromin A, DeGray B, Varshney A, Sharma Y, Szigeti-Buck K, Ehrlich BE. Neuronal calcium sensor-1 enhancement of InsP3 receptor activity is inhibited by therapeutic levels of lithium. J Clin Invest 2006;116(6):1668-74. doi: 10.1172/JCI22466.

Mo M, Erdelyi I, Szigeti-Buck K, Benbow JH, Ehrlich BE. Prevention of paclitaxel-induced peripheral neuropathy by lithium pretreatment. FASEB J 2012;26(11):4696-709. doi: 10.1096/fj.12-214643.

Huehnchen P, Boehmerle W, Springer A, Freyer D, Endres M. A novel preventive therapy for paclitaxel-induced cognitive deficits: preclinical evidence from C57BL/6 mice. Transl Psychiatry 2017;7(8):e1185. doi: 10.1038/tp.2017.149.

Wadia RJ, Stolar M, Grens C, Ehrlich BE, Chao HH. The prevention of chemotherapy induced peripheral neuropathy by concurrent treatment with drugs used for bipolar disease: a retrospective chart analysis in human cancer patients. Oncotarget 2017;9(7):7322-7331. doi: 10.18632/oncotarget.23467.