Official Title
TOTEM RRMS : TestOsterone TreatmEnt on Neuroprotection and Myelin Repair in Relapsing Remitting Multiple Sclerosis
Phase
Phase 2Lead Sponsor
University of StrasbourgStudy Type
InterventionalStatus
RecruitingIndication/Condition
Multiple Sclerosis, Relapsing-RemittingIntervention/Treatment
Nebido® Testosterone Undecanoate 1000 Mg/4 mL Solution for Injection ...Study Participants
40Centra nervous system (CNF) damage in multiple sclerosis (MS), are mainly attributed to myelin destruction, axonal abnormalities and subsequent degeneration, and are responsible for serious deficiencies. Current therapies are focused on the treatment of inflammation with several types of anti-inflammatory agents. However, there is an urgent need for innovative therapies promoting neuroregeneration and particularly myelin repair.
It has been demonstrated that testosterone can act through neural androgen receptors to promote proliferation and differentiation of oligodendrocyte precursors into mature oligodendrocytes in a cuprizone-induced animal model of demyelination. The rare clinical trials on testosterone are mainly exploratory. Here, we sought to demonstrate an effect of testosterone supplementation in testosterone-deficient patients in a multicenter, randomized, parallel-group, double-blind, placebo-controlled phase 2 trial.
The main objective will be to determine the neuroprotective and remyelinating effects of testosterone using tensor diffusion imaging techniques and thalamic atrophy analyzes.
As secondary objectives, we would like to study the impact of testosterone supplementation on other conventional and unconventional MRI parameters and on clinical outcomes (cognition, fatigue, quality of life, impact on work / activity and anxiety / depression).
Active treatment (Nebido® Testosterone Undecanoate ) will be injected at Baseline, at week 6 and then every 12 weeks (Week 18, 30, 42 and 54)
Placebo will be injected at Baseline, at week 6 and then every 12 weeks (Week 18, 30, 42 and 54)
Conventional MS sequences (OFSEP recommendations) and unconventional MRI sequences (Baseline, week 30 and 66)
BICAMS; SF-36 and EQ-5D-3L; MFIS; HADS; WPAI:MS (at baseline, week 30 and 66)
EDSS (Baseline, week 30 and 66)
"Treatment/Nebido®" arm: in this experimental arm, each patient will be injected intramuscularly with 1000 mg / 4 ml of testosterone undecanoate (Nebido®). Treatment will be injected at baseline, week 6, 18, 30, 42 and 54
"Placebo" arm: In this arm, each patient will be injected intramuscularly with 4 ml of placebo solution. Placebo will be injected at baseline, week 6, 18, 30, 42 and 54
Inclusion Criteria: Man between 18 and 55 years Patient affiliated to a social health insurance plan Patient able to understand the objectives and risks related to the research and able to comply with the requirements of the protocol throughout the duration of the study Patient having been informed of the results of the prior medical examination Patient having signed an informed consent Confirmed and documented diagnosis of MS, as defined by the revised McDonald criteria, Patient who have been receiving one of the following disease modifying therapies for at least one year prior to randomization: natalizumab , fingolimod, ocrelizumab, or ofatumumab, in accordance with their prescribing information. Switching from one molecule to another during the previous year is also permitted, provided that the switch was motivated by a non-neurological reason (relapse, MRI activity). Biological hypogonadism defined by serum total testosterone levels below 20 nmol / L (checked by blood sampling during the screening visit) For patients under natalizumab : Negative status for JC virus or JC virus synthesis index ≤ 1.5 (checked by blood sampling at the inclusion visit) No relapses in the year prior to inclusion Disability status during the selection visit with an EDSS score of 0 to 7 (verified by questionnaire during the inclusion visit) Stable neurological state in the month preceding randomization Exclusion Criteria: Patients with progressive MS (primary or secondary) Patients with hypogonadism with clinical symptoms and treated with androgens Patients with PSA (prostate specific antigen)> 2.5 ng / ml (for an age less than 49 years old) or> 3.5 ng / ml (for age ≥ 50 years) (checked by a blood test at the inclusion visit) Patients with a hemoglobin concentration> 16 g / dL (checked by blood sampling during the inclusion visit) Patients refusing or unable to undergo an MRI Patients with any other disease other than MS that may contribute to neurological symptoms and signs or affect their evaluation Patients with neurological signs compatible with progressive multifocal leukoencephalopathy (PML) or confirmed leukoencephalopathy Patients diagnosed with untreated sleep apnea Patients with or having had cancer or tumors of the liver, heart, kidney, prostate or mammary gland Patients with cardiovascular, renal, hepatic, hematological, gastrointestinal, pulmonary, uncontrolled diseases Patients wishing to procreate during the study period Patients with chronic infectious disease Patients with organic or psychiatric disease compromise their ability to understand the information given and to follow the protocol Patients with a history of hypersensitivity to treatment or any of the excipients, or drugs of similar chemical classes Patients who used experimental drugs and / or who participated in clinical drug trials in the 6 months prior to selection Patient in exclusion period (determined by previous study or in progress) Impossibility of giving information to the patient (subject in emergency situation, difficulties in understanding the subject or other) Patients under tutors or curators Patients under the protection of justice
