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TOTEM RRMS : TestOsterone TreatmEnt on Neuroprotection and Myelin Repair in Relapsing Remitting Multiple Sclerosis

Study Purpose

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).

Recruitment Criteria

Accepts Healthy Volunteers Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms	No
Study Type An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes. An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes. Searching Both is inclusive of interventional and observational studies.	Interventional
Eligible Ages	18 Years - 55 Years
Gender	Male

More Inclusion & Exclusion Criteria

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

Trial Details

Trial ID: This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.	NCT03910738
Phase Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans. Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data. Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs. Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.	Phase 2
Lead Sponsor The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.	University Hospital, Strasbourg, France
Principal Investigator The person who is responsible for the scientific and technical direction of the entire clinical study.	Laurent D KREMER, MD
Principal Investigator Affiliation	CHU Strasbourg
Agency Class Category of organization(s) involved as sponsor (and collaborator) supporting the trial.	Other, Industry
Overall Status	Recruiting
Countries	France
Conditions The disease, disorder, syndrome, illness, or injury that is being studied.	Multiple Sclerosis, Relapsing-Remitting

Arms & Interventions

Arms

Experimental: Testosterone treatment (Nebido®)

"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 Comparator: Placebo

"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

Interventions

Drug: - Nebido® Testosterone Undecanoate 1000 Mg/4 mL Solution for Injection

Active treatment (Nebido® Testosterone Undecanoate ) will be injected at Baseline, at week 6 and then every 12 weeks (Week 18, 30, 42 and 54)

Drug: - Placebo 4 mL Solution for Injection

Placebo will be injected at Baseline, at week 6 and then every 12 weeks (Week 18, 30, 42 and 54)

Procedure: - MRI

Conventional MS sequences (OFSEP recommendations) and unconventional MRI sequences (Baseline, week 30 and 66)

Behavioral: - Assessment of impact of MS on cognition; quality of life; fatigue; anxiety/depression and work and activities

BICAMS; SF-36 and EQ-5D-3L; MFIS; HADS; WPAI:MS (at baseline, week 30 and 66)

Behavioral: - Assessment of disability

EDSS (Baseline, week 30 and 66)

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.