Testosterone Treatment for Multiple Sclerosis

• Sponsor: University of California, Los Angeles (Other)
• Overall Status: Completed
• CT.gov ID: NCT00405353
• Collaborator: National Multiple Sclerosis Society (Other)
• Enrollment: 10
• Location: 1
• Arm: 1
• Duration (Months): 59
• Patients Per Site Per Month: 0.2

Study Details

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
• 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: Apr 1, 2002
• Actual Primary Completion Date: Mar 1, 2007
• Actual Study Completion Date: Mar 1, 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 Names: testosterone

Outcome Measures

Primary Outcome Measures

1. Whole Brain Atrophy Rate [Baseline and 12 months]

   as assessed by Voxel-Based Morphometry

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

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

	Site	City	State	Country	Postal Code
1	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

Study Documents (Full-Text)

None provided.

More Information

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: Nov 30, 2006
• Last Update Posted: Nov 22, 2019
• Last Verified: Nov 1, 2019

• Individual Participant Data (IPD) Sharing Statement: No
• 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, Professor, Department of Neurology; Director Multiple Sclerosis Program, University of California, Los Angeles: multiple sclerosis; testosterone
• Additional relevant MeSH terms: Multiple Sclerosis; Sclerosis; Methyltestosterone; Testosterone; Testosterone undecanoate; Testosterone enanthate; Testosterone 17 beta-cypionate

Study Results

Participant Flow

Arm/Group Title	Testosterone Arm/ Group
Arm/Group Description	All subjects underwent a 6-month observation period, followed by 12 months of open label testosterone treatment, using 10g of gel containing 100mg of testosterone (Androgel) applied topically.
Period Title: Overall Study
STARTED	10
COMPLETED	10
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Testosterone Arm/ Group
Arm/Group Description	All subjects underwent a 6-month observation period, followed by 12 months of open label testosterone treatment, using 10g of gel containing 100mg of testosterone (Androgel) applied topically. Brain MRIs were obtained every month from baseline (month 0) until the end of the trial (month 18). All 10 subjects completed all nineteen monthly scans.
Overall Participants	10
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	10 100%
>=65 years	0 0%
Sex/Gender, Customized (patients) [Number]
Male	10
Region of Enrollment (participants) [Number]
United States	10 100%

Outcome Measures

1. Primary Outcome

Title	Whole Brain Atrophy Rate
Description	as assessed by Voxel-Based Morphometry
Time Frame	Baseline and 12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Testosterone Arm/ Group
Arm/Group Description	All subjects underwent a 6-month observation period, followed by 12 months of open label testosterone treatment, using 10g of gel containing 100mg of testosterone (Androgel) applied topically.
Measure Participants	10
Mean (95% Confidence Interval) [percent change in brain volume]	.82

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Testosterone Arm/ Group
	Comments	Percent change in brain volume against time scatter plot with a Loess regression curve was produced and a first-degree spline model was developed. This model fitted line pieces for pre-treatment and early treatment periods (month -6 to month 3) and treatment response period (months 3-12), and these pieces were joined together to achieve continuity. Slopes of these lines were estimated and compared. A random intercept was set in the model to allow the difference among subjects.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.05
	Comments
	Method	Mixed Models Analysis
	Comments	Linear regressions were used to determine slopes of brain volume changes. Statistical software package SAS was used to perform the analysis.

Adverse Events

Time Frame	18 months
Adverse Event Reporting Description	All subjects underwent a 6-month observation period, followed by 12 months of open label testosterone treatment, using 10g of gel containing 100mg of testosterone (Androgel) applied topically.
Arm/Group Title	Testosterone Arm/ Group
Arm/Group Description	All subjects underwent a 6-month observation period, followed by 12 months of open label testosterone treatment, using 10g of gel containing 100mg of testosterone (Androgel) applied topically.
All Cause Mortality
	Testosterone Arm/ Group
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Testosterone Arm/ Group
	Affected / at Risk (%)	# Events
Total	0/10 (0%)
Other (Not Including Serious) Adverse Events
	Testosterone Arm/ Group
	Affected / at Risk (%)	# Events
Total	0/10 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.