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The TOTEM RRMS (Testosterone Treatment on neuroprotection and Myelin Repair in Relapsing Remitting Multiple Sclerosis) trial: study protocol for a randomized, double-blind, placebo-controlled trial
- Source :
- Trials, Vol 21, Iss 1, Pp 1-11 (2020), Trials, Trials, 2020, 21, ⟨10.1186/s13063-020-04517-6⟩
- Publication Year :
- 2020
- Publisher :
- BMC, 2020.
-
Abstract
- Background Central nervous system damage in multiple sclerosis (MS) is responsible for serious deficiencies. Current therapies are focused on the treatment of inflammation; however, there is an urgent need for innovative therapies promoting neuroregeneration, particularly myelin repair. It is demonstrated that testosterone can act through neural androgen receptors and several clinical observations stimulated an interest in the potential protective effects of testosterone treatment for MS. Here, we sought to demonstrate the effects of a testosterone supplementation in testosterone-deficient men with relapsing-remitting MS. Methods/design This report presents the rationale and methodology of TOTEM RRMS, a French, phase 2, multicenter, randomized, placebo-controlled, and double-blind trial, which aims to prevent the progression of MS in men with low testosterone levels by administration of testosterone undecanoate, who were kept under natalizumab (Tysabri®) to overcome the anti-inflammatory effect of testosterone. Forty patients will be randomized into two groups receiving either a testosterone treatment (Nebido®) or a matching placebo. The intervention period for each group will last 66 weeks (treatment will be injected at baseline, week 6, and then every 12 weeks). The main objective is to determine the neuroprotective and remyelinating effects of testosterone using tensor diffusion imaging techniques and thalamic atrophy analyses. As secondary objectives, impacts of the testosterone supplementation will be studied using other conventional and unconventional MRI parameters and with clinical outcomes. Discussion The action of testosterone is observed in different experimental autoimmune encephalomyelitis models and epidemiological studies in humans. However, despite several preclinical data and some small clinical trials in MS, clear evidence for a therapeutic effect of hormone therapy is still missing. Therefore, our goal is to demonstrate the effects of testosterone therapies in MS. As there is no effective treatment currently available on fatigue in MS, careful attention should also be paid to secondary endpoints: fatigue, cognitive functions, and other symptoms that may improve life quality. Assuming a positive outcome of the trial, this treatment could be considered as a new neuroprotective and remyelinating therapy in relapsing-remitting MS and could be applicable to other demyelinating diseases. Trial registration ClinicalTrials.gov NCT03910738. Registered on 10 April 2019.
- Subjects :
- Oncology
Male
medicine.medical_specialty
medicine.medical_treatment
Placebo-controlled study
Medicine (miscellaneous)
Placebo
law.invention
Multiple sclerosis
03 medical and health sciences
Study Protocol
0302 clinical medicine
Natalizumab
Multiple Sclerosis, Relapsing-Remitting
Randomized controlled trial
Double-Blind Method
law
Internal medicine
Medicine
Humans
Multicenter Studies as Topic
Pharmacology (medical)
Testosterone
Myelin Sheath
Randomized Controlled Trials as Topic
lcsh:R5-920
business.industry
medicine.disease
Magnetic Resonance Imaging
Neuroprotection
Clinical trial
Treatment Outcome
Remyelination
[INFO.INFO-TI]Computer Science [cs]/Image Processing [eess.IV]
030220 oncology & carcinogenesis
Disease Progression
Hormone therapy
business
lcsh:Medicine (General)
030217 neurology & neurosurgery
medicine.drug
Subjects
Details
- Language :
- English
- ISSN :
- 17456215
- Volume :
- 21
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Trials
- Accession number :
- edsair.doi.dedup.....09d5d786c8dab72fa59f90888989af23