TOTEM RRMS : TestOsterone TreatmEnt on Neuroprotection and Myelin Repair in Relapsing Remitting Multiple Sclerosis
TOTEM RRMS : TestOsterone TreatmEnt on Neuroprotection and Myelin Repair in Relapsing Remitting Multiple Sclerosis
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).
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 treated with intravenous infusions of natalizumab (Tysabri®, 300 mg) once
 every 4 weeks for at least 1 year

 -  Biological hypogonadism defined by serum testosterone levels below 15 nmol / L
 (checked by blood sampling during the inclusion visit)

 -  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