Testosterone for Fatigue in Men With MS

NCT03000127 | Withdrawn Phase 2 FDA Drug

• 1 other identifier: 1R01NS102295
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 2

Brief Summary

Fatigue is a major symptom in people with multiple sclerosis (MS), for which treatments are limited. Several studies have shown that a large proportion of men with MS have low testosterone levels. We propose a two-site clinical trial using topical testosterone gel as a treatment for MS-related fatigue in men with progressive MS who have low or low-normal testosterone levels.

Conditions

Multiple Sclerosis

Keywords

testosterone; multiple sclerosis; fatigue

Outcome Measures

Primary Outcomes (1)

• Modified Fatigue Impact Scale (MFIS)

  assessment of fatigue severity

  18 months

Secondary Outcomes (2)

• Localized Gray Matter Atrophy

  18 months

• Axon Density in White Matter

  18 months

Other Outcomes (3)

• Correlation of testosterone level with fatigue

  18 months

• Correlation of localized gray matter atrophy with fatigue

  18 months

• Correlation of axon density in white matter with fatigue

  18 months

Study Arms (1)

Single arm crossover

EXPERIMENTAL

All patients will receive testosterone gel and placebo gel during some months, but the months that they are on each treatment will be unknown to the patient

Drug: AndroGel 1 % Topical Gel; Drug: Placebos

Interventions

AndroGel 1 % Topical Gel DRUG

testosterone gel

Single arm crossover

Placebos DRUG

Placebo gel

Single arm crossover

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• \) Men with SPMS or PPMS, 2)18-60 years old, 3) EDSS of 1.0- 6.5, 4) Low or low-normal T \< 499ng/dL and 5) FSS scores of \>3.6.

You may not qualify if:

• \) Prostate specific antigen \> 2.5 (\<49yr of age) or \>3.5 (age \>50yr of age), 2) baseline hematocrit greater than the upper limit of normal for the laboratory used, 3) EKG with ischemic changes, 4) history of myocardial infarction, unstable angina, stroke, transient ischemic attack, or deep vein thrombosis, 5) history of prostate or breast cancer, 6) screening T level \>500ng/dL, 7) diabetes requiring treatment, 8) current drug/alcohol abuse, 9) disease other than MS causing fatigue, such as obstructive sleep apnea or other sleep disorder, or untreated thyroid dysfunction, 10) RRMS, 11) Beck Depression Inventory-II (BDI) score over 20, 12) cognitive dysfunction such that subject cannot perform study tests, 13) inability to undergo MRI, 14) current or expected use of amphetamines, or 15) anticipated changes in medical treatments that might affect fatigue scores (e.g., expected changes in spasticity, sleep, or depression medications).

Sponsors & Collaborators

• University of California, Los Angeles: lead
• Washington University School of Medicine: collaborator

Study Sites (2)

University of California, Los Angeles

Los Angeles, California, 90095, United States

Location

Washington University

St Louis, Missouri, 63110, United States

Location

Related Publications (11)

• Sicotte NL, Giesser BS, Tandon V, Klutch R, Steiner B, Drain AE, Shattuck DW, Hull L, Wang HJ, Elashoff RM, Swerdloff RS, Voskuhl RR. Testosterone treatment in multiple sclerosis: a pilot study. Arch Neurol. 2007 May;64(5):683-8. doi: 10.1001/archneur.64.5.683.

  PMID: 17502467 BACKGROUND

• Kurth F, Luders E, Sicotte NL, Gaser C, Giesser BS, Swerdloff RS, Montag MJ, Voskuhl RR, Mackenzie-Graham A. Neuroprotective effects of testosterone treatment in men with multiple sclerosis. Neuroimage Clin. 2014 Mar 6;4:454-60. doi: 10.1016/j.nicl.2014.03.001. eCollection 2014.

  PMID: 24634831 BACKGROUND

• Gold SM, Chalifoux S, Giesser BS, Voskuhl RR. Immune modulation and increased neurotrophic factor production in multiple sclerosis patients treated with testosterone. J Neuroinflammation. 2008 Jul 31;5:32. doi: 10.1186/1742-2094-5-32.

  PMID: 18671877 BACKGROUND

• Ziehn MO, Avedisian AA, Dervin SM, Umeda EA, O'Dell TJ, Voskuhl RR. Therapeutic testosterone administration preserves excitatory synaptic transmission in the hippocampus during autoimmune demyelinating disease. J Neurosci. 2012 Sep 5;32(36):12312-24. doi: 10.1523/JNEUROSCI.2796-12.2012.

  PMID: 22956822 BACKGROUND

• Gold SM, Voskuhl RR. Estrogen and testosterone therapies in multiple sclerosis. Prog Brain Res. 2009;175:239-51. doi: 10.1016/S0079-6123(09)17516-7.

  PMID: 19660660 BACKGROUND

• Liva SM, Voskuhl RR. Testosterone acts directly on CD4+ T lymphocytes to increase IL-10 production. J Immunol. 2001 Aug 15;167(4):2060-7. doi: 10.4049/jimmunol.167.4.2060.

  PMID: 11489988 BACKGROUND

• Dalal M, Kim S, Voskuhl RR. Testosterone therapy ameliorates experimental autoimmune encephalomyelitis and induces a T helper 2 bias in the autoantigen-specific T lymphocyte response. J Immunol. 1997 Jul 1;159(1):3-6.

  PMID: 9200430 BACKGROUND

• Golden LC, Voskuhl R. The importance of studying sex differences in disease: The example of multiple sclerosis. J Neurosci Res. 2017 Jan 2;95(1-2):633-643. doi: 10.1002/jnr.23955.

  PMID: 27870415 BACKGROUND

• Spence RD, Voskuhl RR. Neuroprotective effects of estrogens and androgens in CNS inflammation and neurodegeneration. Front Neuroendocrinol. 2012 Jan;33(1):105-15. doi: 10.1016/j.yfrne.2011.12.001. Epub 2011 Dec 24.

  PMID: 22209870 BACKGROUND

• Hussain R, Ghoumari AM, Bielecki B, Steibel J, Boehm N, Liere P, Macklin WB, Kumar N, Habert R, Mhaouty-Kodja S, Tronche F, Sitruk-Ware R, Schumacher M, Ghandour MS. The neural androgen receptor: a therapeutic target for myelin repair in chronic demyelination. Brain. 2013 Jan;136(Pt 1):132-46. doi: 10.1093/brain/aws284.

  PMID: 23365095 BACKGROUND

• Voskuhl RR, Gold SM. Sex-related factors in multiple sclerosis susceptibility and progression. Nat Rev Neurol. 2012 Mar 27;8(5):255-63. doi: 10.1038/nrneurol.2012.43.

  PMID: 22450508 BACKGROUND

MeSH Terms

Conditions

Multiple Sclerosis; Fatigue

Interventions

Testosterone; Gels

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Androstenols; Androstenes; Androstanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Testosterone Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Colloids; Complex Mixtures; Dosage Forms; Pharmaceutical Preparations

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Masking Details: All patients will receive either testosterone or placebo at some phase of treatment, but which phase will be testosterone and which will be placebo will be unknown (blinded) to participant, care provider, and outcomes assessor.
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, Department of Neurology

Model Details: Single arm, testosterone or placebo will be administered to all patients at some period of study, but which period of study the they will recieve placebo or testosterone gel will be blinded (unknown) to participant, care provider, and outcomes assessor.

Study Record Dates

• First Submitted: December 17, 2016
• First Posted: December 21, 2016
• Study Start: July 1, 2018
• Primary Completion: June 30, 2023
• Study Completion: January 1, 2024
• Last Updated: November 6, 2019

Record last verified: 2019-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)