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
Abstract Background Central nervous system damage in multiple sclerosis (MS) is responsible for serious deficiencies. Current therapies are focused on the treatment of inflammation; however, there is an urgent need for innovative therapies promoting neuroregeneration, particularly myelin repair. It...
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| Format: | Article |
| Language: | English |
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BMC
2020-06-01
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| Series: | Trials |
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| Online Access: | http://link.springer.com/article/10.1186/s13063-020-04517-6 |
| _version_ | 1819033352624144384 |
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| author | Katline Metzger-Peter Laurent Daniel Kremer Gilles Edan Paulo Loureiro De Sousa Julien Lamy Dominique Bagnard Ayikoe-Guy Mensah-Nyagan Thibault Tricard Guillaume Mathey Marc Debouverie Eric Berger Anne Kerbrat Nicolas Meyer Jérôme De Seze Nicolas Collongues |
| author_facet | Katline Metzger-Peter Laurent Daniel Kremer Gilles Edan Paulo Loureiro De Sousa Julien Lamy Dominique Bagnard Ayikoe-Guy Mensah-Nyagan Thibault Tricard Guillaume Mathey Marc Debouverie Eric Berger Anne Kerbrat Nicolas Meyer Jérôme De Seze Nicolas Collongues |
| author_sort | Katline Metzger-Peter |
| collection | DOAJ |
| description | Abstract Background Central nervous system damage in multiple sclerosis (MS) is responsible for serious deficiencies. Current therapies are focused on the treatment of inflammation; however, there is an urgent need for innovative therapies promoting neuroregeneration, particularly myelin repair. It is demonstrated that testosterone can act through neural androgen receptors and several clinical observations stimulated an interest in the potential protective effects of testosterone treatment for MS. Here, we sought to demonstrate the effects of a testosterone supplementation in testosterone-deficient men with relapsing-remitting MS. Methods/design This report presents the rationale and methodology of TOTEM RRMS, a French, phase 2, multicenter, randomized, placebo-controlled, and double-blind trial, which aims to prevent the progression of MS in men with low testosterone levels by administration of testosterone undecanoate, who were kept under natalizumab (Tysabri®) to overcome the anti-inflammatory effect of testosterone. Forty patients will be randomized into two groups receiving either a testosterone treatment (Nebido®) or a matching placebo. The intervention period for each group will last 66 weeks (treatment will be injected at baseline, week 6, and then every 12 weeks). The main objective is to determine the neuroprotective and remyelinating effects of testosterone using tensor diffusion imaging techniques and thalamic atrophy analyses. As secondary objectives, impacts of the testosterone supplementation will be studied using other conventional and unconventional MRI parameters and with clinical outcomes. Discussion The action of testosterone is observed in different experimental autoimmune encephalomyelitis models and epidemiological studies in humans. However, despite several preclinical data and some small clinical trials in MS, clear evidence for a therapeutic effect of hormone therapy is still missing. Therefore, our goal is to demonstrate the effects of testosterone therapies in MS. As there is no effective treatment currently available on fatigue in MS, careful attention should also be paid to secondary endpoints: fatigue, cognitive functions, and other symptoms that may improve life quality. Assuming a positive outcome of the trial, this treatment could be considered as a new neuroprotective and remyelinating therapy in relapsing-remitting MS and could be applicable to other demyelinating diseases. Trial registration ClinicalTrials.gov NCT03910738. Registered on 10 April 2019. |
| first_indexed | 2024-12-21T07:16:29Z |
| format | Article |
| id | doaj.art-b37de76ed73045908c261ab84e917929 |
| institution | Directory Open Access Journal |
| issn | 1745-6215 |
| language | English |
| last_indexed | 2024-12-21T07:16:29Z |
| publishDate | 2020-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Trials |
| spelling | doaj.art-b37de76ed73045908c261ab84e9179292022-12-21T19:11:52ZengBMCTrials1745-62152020-06-0121111110.1186/s13063-020-04517-6The TOTEM RRMS (Testosterone Treatment on neuroprotection and Myelin Repair in Relapsing Remitting Multiple Sclerosis) trial: study protocol for a randomized, double-blind, placebo-controlled trialKatline Metzger-Peter0Laurent Daniel Kremer1Gilles Edan2Paulo Loureiro De Sousa3Julien Lamy4Dominique Bagnard5Ayikoe-Guy Mensah-Nyagan6Thibault Tricard7Guillaume Mathey8Marc Debouverie9Eric Berger10Anne Kerbrat11Nicolas Meyer12Jérôme De Seze13Nicolas Collongues14Centre d᾿Investigation Clinique INSERM 1434Departement of Neurology, Hôpital de Hautepierre, University Hospital of StrasbourgDepartement of Neurology, Hôpital Pontchaillou, University Hospital of RennesLaboratory of Engineering Sciences, Computer Science and Imagery (ICube), CNRS, Institute of Biological Physics, University of StrasbourgLaboratory of Engineering Sciences, Computer Science and Imagery (ICube), CNRS, Institute of Biological Physics, University of StrasbourgDepartement of Myelin Biopathology, Neuroprotection and Therapeutic Strategies, UMR_S Inserm 1119Departement of Myelin Biopathology, Neuroprotection and Therapeutic Strategies, UMR_S Inserm 1119Departement of Urological Surgery, Nouvel Hôpital Civil, University Hospital of StrasbourgDepartement of Neurology, Hôpital Central, University Hospital of NancyDepartement of Neurology, Hôpital Central, University Hospital of NancyDepartement of Neurology, Hôpital Jean Minjoz, University Hospital of BesançonDepartment of Neurology, Hôpital de Pontchaillou, University Hospital of RennesDepartement of Public Health, GMRC University Hospital of StrasbourgCentre d᾿Investigation Clinique INSERM 1434Centre d᾿Investigation Clinique INSERM 1434Abstract Background Central nervous system damage in multiple sclerosis (MS) is responsible for serious deficiencies. Current therapies are focused on the treatment of inflammation; however, there is an urgent need for innovative therapies promoting neuroregeneration, particularly myelin repair. It is demonstrated that testosterone can act through neural androgen receptors and several clinical observations stimulated an interest in the potential protective effects of testosterone treatment for MS. Here, we sought to demonstrate the effects of a testosterone supplementation in testosterone-deficient men with relapsing-remitting MS. Methods/design This report presents the rationale and methodology of TOTEM RRMS, a French, phase 2, multicenter, randomized, placebo-controlled, and double-blind trial, which aims to prevent the progression of MS in men with low testosterone levels by administration of testosterone undecanoate, who were kept under natalizumab (Tysabri®) to overcome the anti-inflammatory effect of testosterone. Forty patients will be randomized into two groups receiving either a testosterone treatment (Nebido®) or a matching placebo. The intervention period for each group will last 66 weeks (treatment will be injected at baseline, week 6, and then every 12 weeks). The main objective is to determine the neuroprotective and remyelinating effects of testosterone using tensor diffusion imaging techniques and thalamic atrophy analyses. As secondary objectives, impacts of the testosterone supplementation will be studied using other conventional and unconventional MRI parameters and with clinical outcomes. Discussion The action of testosterone is observed in different experimental autoimmune encephalomyelitis models and epidemiological studies in humans. However, despite several preclinical data and some small clinical trials in MS, clear evidence for a therapeutic effect of hormone therapy is still missing. Therefore, our goal is to demonstrate the effects of testosterone therapies in MS. As there is no effective treatment currently available on fatigue in MS, careful attention should also be paid to secondary endpoints: fatigue, cognitive functions, and other symptoms that may improve life quality. Assuming a positive outcome of the trial, this treatment could be considered as a new neuroprotective and remyelinating therapy in relapsing-remitting MS and could be applicable to other demyelinating diseases. Trial registration ClinicalTrials.gov NCT03910738. Registered on 10 April 2019.http://link.springer.com/article/10.1186/s13063-020-04517-6Multiple sclerosisTestosteroneNeuroprotectionRemyelinationRandomized controlled trial |
| spellingShingle | Katline Metzger-Peter Laurent Daniel Kremer Gilles Edan Paulo Loureiro De Sousa Julien Lamy Dominique Bagnard Ayikoe-Guy Mensah-Nyagan Thibault Tricard Guillaume Mathey Marc Debouverie Eric Berger Anne Kerbrat Nicolas Meyer Jérôme De Seze Nicolas Collongues 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 Multiple sclerosis Testosterone Neuroprotection Remyelination Randomized controlled trial |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| topic | Multiple sclerosis Testosterone Neuroprotection Remyelination Randomized controlled trial |
| url | http://link.springer.com/article/10.1186/s13063-020-04517-6 |
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