Testosterone Treatment for Multiple Sclerosis

• ClinicalTrials.gov Identifier: NCT00405353
• Recruitment Status: Completed
• First Posted: November 30, 2006
• Results First Posted: November 22, 2019
• Last Update Posted: November 22, 2019
• Sponsor: University of California, Los Angeles
• Collaborator: National Multiple Sclerosis Society
• Information provided by (Responsible Party): Rhonda Voskuhl, University of California, Los Angeles

Study Description

Brief Summary:

Since men are less likely to develop multiple sclerosis, the hypothesis was that testosterone might be protective in MS. Men with MS for followed untreated for 6 months, followed by a 12 month treatment period with Androgel.

Condition or disease	Intervention/treatment	Phase
Multiple Sclerosis	Drug: Androgel 10 grams of gel containing 100 mg of testosterone	Phase 1; Phase 2

Detailed Description:

Background: Men are less susceptible to many autoimmune diseases including multiple sclerosis (MS). Possible causes for this include sex hormones and/or sex chromosome effects. Testosterone treatment ameliorates experimental allergic encephalomyelitis (EAE), an animal model of MS, but the effect of testosterone supplementation on men with MS is not known.

Design, Setting and Participants: Ten men with relapsing remitting MS were studied using a crossover design whereby each patient served as his own control. There was a six-month pretreatment period followed by a twelve month period of daily treatment with 100mg of testosterone gel.

Main Outcome Measures: Brain atrophy and Cognitive testing

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 10 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Testosterone Treatment for Multiple Sclerosis: A Preliminary Trial
• Study Start Date: April 2002
• Actual Primary Completion Date: March 2007
• Actual Study Completion Date: March 2007

Arms and Interventions

Arm	Intervention/treatment
Experimental: crossover treatment with Androgel; 6 months pretreatment, 12 months treatment intervention with Androgel 10 grams of gel containing 100mg of testosterone	Drug: Androgel 10 grams of gel containing 100 mg of testosterone; testosterone gel; Other Name: testosterone

Outcome Measures

Primary Outcome Measures :

1. Whole Brain Atrophy Rate [ Time Frame: Baseline and 12 months ]
   as assessed by Voxel-Based Morphometry

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Men, age 18-65, with a diagnosis of clinically definite relapsing remitting multiple sclerosis.
2. Relapsing remitting patients who have declined or not tolerated treatment with beta interferon (Betaseron, Avonex) or glatiramer acetate, copolymer-1 (Copaxone).
3. At least one relapse in the two years prior to entry. Relapse will be defined historically as definite worsening of a previous symptom (over 0-3 days) or development of a new symptom (over 0-3 days).
4. Not in an intercurrent relapse.
5. Expanded Disability Status Score (EDSS) = 0.0 to 5.0.
6. The patients must have a significant T2 burden of disease on screening cerebral MRI as defined by T2 lesion loads greater than 7.5cm3.
7. Must live within 100 miles of UCLA.
8. Must be willing and able to receive an initial screening cerebral MRI, a baseline MRI and monthly cerebral MRIs (with and without gadolinium) for a total period of 12 months (6 months prior to treatment and 6 months during treatment).

Exclusion Criteria:

1. Males unable to fulfill the above criteria and all female patients.
2. Males who have been on sex hormone treatment including androgens, estrogens, or anti-estrogens for hypogonadism or other medical condition during the 12 months prior to study.
3. Males who have taken DHEA during the 3 months prior to study.
4. Patients who have thrombosis, serious cardiac, pulmonary, renal, gastrointestinal, hepatic, immunologic, infectious, neoplastic (with particular focus on patients with known or suspected estrogen or testosterone-dependent tumors), or urologic disease (with a particular focus on patients with a history of prostatic hypertrophy/nodules).
5. Patients with an abnormal prostate as evidenced by prostatic masses or induration on rectal examination or prostate ultrasonography or elevated levels of prostatic specific antigen (PSA 4 ng/ml or higher).
6. Patients with testicular mass on exam.
7. Patients with hematocrit greater than 50%
8. Patients with major psychiatric illness (e.g. manic depressive states, schizophrenia)
9. Patients with active alcoholism.
10. Patients with a history of drug abuse within the past five years.
11. Patients who are greater than 130% or less than 80% of their ideal body weight based on Metropolitan Life Tables.
12. Patients with generalized skin disease that may effect absorption of testosterone (e.g. psoriasis) or a known skin intolerance to alcohol.
13. Patients with prolactin > 40 mcg/L.
14. Patients with a cholesterol level greater than 300 mg/dl.
15. Patients with other conditions that would interfere with assessing neurologic functions such as deforming arthritis or a major amputation.
16. Patients who have received treatment with beta interferon (Betaseron or Avonex), glatiramer acetate copolymer-1 (Copaxone), ACTH, corticosteroids, intravenous immunoglobulins (IVIG), or plasma exchange in the three months preceding enrollment
17. Patients who have received treatment with azathioprine, cyclophosphamide, methotrexate, mitoxantrone, cyclosporin A or experimental therapies in the six months preceding enrollment.
18. Patients who have been treated with total lymphoid irradiation, monoclonal antibody, T cell vaccination, cladribine or bone marrow transplantation.
19. Patients who have positive titers to HIV1,2; HTLV1; or VDRL.
20. Patients who have clinical evidence of Lyme disease.
21. Patients who are mentally or emotionally incompetent in the opinion of the examining neurologist or unable to give informed consent, or to understand and comply with the study protocol.
22. Patients with certain artificial heart valves, pacemakers, or other metallic/electronic material in their bodies.
23. Patients with known hypersensitivity to gadolinium-DPTA.

Contacts and Locations

Locations

United States, California

University of California, Los Angeles

Los Angeles, California, United States, 90095

Sponsors and Collaborators

University of California, Los Angeles

National Multiple Sclerosis Society

Investigators

• Principal Investigator: Rhonda Voskuhl, M.D.; University of California, Los Angeles

More Information

Publications of Results:

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.

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.

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.

Other Publications:

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.

• Responsible Party: Rhonda Voskuhl, Professor, Department of Neurology; Director Multiple Sclerosis Program, University of California, Los Angeles
• ClinicalTrials.gov Identifier: NCT00405353
• Other Study ID Numbers: RG 3239
• First Posted: November 30, 2006
• Results First Posted: November 22, 2019
• Last Update Posted: November 22, 2019
• Last Verified: November 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Rhonda Voskuhl, University of California, Los Angeles:

multiple sclerosis; testosterone

Additional relevant MeSH terms:

Multiple Sclerosis; Sclerosis; Pathologic Processes; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases; Methyltestosterone; Testosterone; Testosterone undecanoate; Testosterone enanthate; Testosterone 17 beta-cypionate; Androgens; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Antineoplastic Agents, Hormonal; Antineoplastic Agents; Anabolic Agents