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

NCT ID: NCT03910738

Last Updated: 2025-06-29

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

40 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-10-29

Study Completion Date

2027-12-31

Brief Summary

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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).

Detailed Description

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Conditions

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Multiple Sclerosis, Relapsing-Remitting

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

multicenter, randomized, parallel-group, double-blind, placebo-controlled phase 2 trial
Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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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

Group Type EXPERIMENTAL

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

Intervention Type DRUG

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

MRI

Intervention Type PROCEDURE

Conventional 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

Intervention Type BEHAVIORAL

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

Assessment of disability

Intervention Type BEHAVIORAL

EDSS (Baseline, week 30 and 66)

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

Group Type PLACEBO_COMPARATOR

Placebo 4 mL Solution for Injection

Intervention Type DRUG

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

MRI

Intervention Type PROCEDURE

Conventional 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

Intervention Type BEHAVIORAL

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

Assessment of disability

Intervention Type BEHAVIORAL

EDSS (Baseline, week 30 and 66)

Interventions

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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)

Intervention Type 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)

Intervention Type DRUG

MRI

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

Intervention Type PROCEDURE

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)

Intervention Type BEHAVIORAL

Assessment of disability

EDSS (Baseline, week 30 and 66)

Intervention Type BEHAVIORAL

Eligibility Criteria

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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, ponesimod, 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). Patients receiving ocrelizumab within 6 to 9 months are eligible, provided they have received full-dose ocrelizumab for at least 2 years.
* 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 hematocrit level \> 54% (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)
* Incapacitated subject (subject to a legal protection measure: safeguard of justice, curatorship, guardianship, future protection mandate, family habilitation)
Minimum Eligible Age

18 Years

Maximum Eligible Age

55 Years

Eligible Sex

MALE

Accepts Healthy Volunteers

No

Sponsors

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Bayer

INDUSTRY

Sponsor Role collaborator

Fédération Hospitalo-Universitaire NEUROGENYCS

UNKNOWN

Sponsor Role collaborator

Grünenthal GmbH

INDUSTRY

Sponsor Role collaborator

University Hospital, Strasbourg, France

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Laurent D KREMER, MD

Role: PRINCIPAL_INVESTIGATOR

CHU Strasbourg

Locations

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CHU de Besançon

Besançon, , France

Site Status RECRUITING

CHU Nancy

Nancy, , France

Site Status RECRUITING

Hôpital Pitié-Salpêtrière

Paris, , France

Site Status RECRUITING

CHU de Rennes/Pontchaillou

Rennes, , France

Site Status RECRUITING

CHRU de Strasbourg

Strasbourg, , France

Site Status RECRUITING

Countries

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France

Central Contacts

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Laurent D KREMER, MD

Role: CONTACT

+333 88 12 87 33

Nicolas COLLONGUES, MD

Role: CONTACT

+333 88 12 87 33

Facility Contacts

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Eric BERGER, MD

Role: primary

+333 81 66 84 68

Guillaume MATHEY, MD

Role: primary

+333 83 85 16 88

Céline Dr LOUAPRE, Dr

Role: primary

00331 42 16 57 66

Laure MICHEL, MD

Role: primary

+332 99 28 42 66

Laurent D KREMER, MD

Role: primary

+333 88 12 87 33

Nicolas COLLONGUES, MD

Role: backup

+333 88 12 87 33

References

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Metzger-Peter K, Kremer LD, Edan G, Loureiro De Sousa P, Lamy J, Bagnard D, Mensah-Nyagan AG, Tricard T, Mathey G, Debouverie M, Berger E, Kerbrat A, Meyer N, De Seze J, Collongues N. The TOTEM RRMS (Testosterone Treatment on neuroprotection and Myelin Repair in Relapsing Remitting Multiple Sclerosis) trial: study protocol for a randomized, double-blind, placebo-controlled trial. Trials. 2020 Jun 29;21(1):591. doi: 10.1186/s13063-020-04517-6.

Reference Type DERIVED
PMID: 32600454 (View on PubMed)

Other Identifiers

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7109

Identifier Type: -

Identifier Source: org_study_id

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