Centra 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).
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
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 hematocrit level > 54% (checked by blood sampling during the inclusion visit)
Parallel
Nebido® Testosterone Undecanoate 1000 Mg/4 mL Solution for Injection
DrugActive treatment (Nebido® Testosterone Undecanoate ) will be injected at Baseline, at week 6 and then every 12 weeks (Week 18, 30, 42 and 54)
Placebo 4 mL Solution for Injection
DrugPlacebo will be injected at Baseline, at week 6 and then every 12 weeks (Week 18, 30, 42 and 54)
MRI
Procedure/SurgeryConventional MS sequences (OFSEP recommendations) and unconventional MRI sequences (Baseline, week 30 and 66)
Assessment of impact of MS on cognition; quality of life; fatigue; anxiety/depression and work and activities
BehavioralBICAMS; SF-36 and EQ-5D-3L; MFIS; HADS; WPAI:MS (at baseline, week 30 and 66)
Assessment of disability
BehavioralEDSS (Baseline, week 30 and 66)
Change on MRI binary criterion combining thalamic atrophy and modification in transverse diffusivity of lesions
The primary endpoint is a binary criterion comparing the success rate in each treatment group, defined by thalamic atrophy lower than 0.5% and modification in transverse diffusivity of lesions lower than 0.5% per year compared between baseline and week 66 in each group.
Evolution of the number of T1 hypointense lesions as detected by conventional MRI
Efficacy will be assessed by comparing results between the 2 groups and in each group between baseline, week 30 and week 66.
Evolution of the volume of T1 hypointense lesions as detected by conventional MRIconventional MRI
Efficacy will be assessed by comparing results between the 2 groups and in each group between baseline, week 30 and week 66.
Evolution of the number of new or enlarged T2 lesions as detected by conventional MRI
Efficacy will be assessed by comparing results between the 2 groups and in each group between baseline, week 30 and week 66.
Evolution of the volume of new or enlarged T2 lesions as detected by conventional MRI
Efficacy will be assessed by comparing results between the 2 groups and in each group between baseline, week 30 and week 66.
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University Hospital, Strasbourg, France
Lead sponsor
Bayer
Collaborator
Fédération Hospitalo-Universitaire NEUROGENYCS
Collaborator
Grünenthal GmbH
Collaborator
