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

Summary

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).

Conditions

• Multiple Sclerosis, Relapsing-Remitting

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)

Sponsors & Collaborators

• Bayer

  collaborator INDUSTRY

• Fédération Hospitalo-Universitaire NEUROGENYCS

  collaborator UNKNOWN

• Grünenthal GmbH

  collaborator INDUSTRY

• University Hospital, Strasbourg, France

  lead OTHER

Principal Investigators

• Laurent D KREMER, MD · CHU Strasbourg

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

55 Years

Sex

MALE

Healthy Volunteers

No

Timeline & Regulatory

Start

2019-10-29

Primary Completion

2027-12-31

Completion

2027-12-31

Countries

• France

Study Locations