Testosterone Treatment for Multiple Sclerosis

Condition(s) targeted: Multiple Sclerosis

Intervention: Androgel 100mg gel (Drug)

Status: Completed

Sponsored by: University of California, Los Angeles

Official(s) and/or principal investigator(s):
Rhonda Voskuhl, M.D., Principal Investigator, Affiliation: University of California, Los Angeles

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.

Official title: Testosterone Treatment for Multiple Sclerosis: A Preliminary Trial

Study design: Observational, Natural History, Longitudinal, Defined Population, Prospective Study

Detailed description: While testosterone (T) has been previously shown to be safe and well tolerated in hypogonadol males, it has not been previously given to male MS patients. This study will determine whether treatment with testosterone (T), as a percutaneous gel, is safe and well tolerated in male patients with relapsing MS through the following approach. Patients will be followed clinically and with serological studies 6 months prior to treatment to establish baseline data. Then, testosterone (T) gel will be administered daily at 100 mg per day for 6 months. Patients will continue to be followed clinically and with serological studies. Toxic effects of T gel treatment will become evident if patients change during treatment as compared to their baseline. To determine if T gel treatment induces a decrease in MS disease activity, the most sensitive measure will be used, the number and volume of gadolinium enhancing lesions and the volume of T2 lesions on serial cerebral magnetic resonance imaging (MRI). 12 patients will undergo MRI once a month, for 6 consecutive months, before starting treatment to establish their baseline level of disease activity on MRI. Then these 12 patients will be treated with T gel for 6 months. Patients will continue to undergo serial MRI once a month, for 6 more consecutive months, while on treatment. In this manner, the level of disease activity during treatment can be compared to the level of disease activity before treatment. Patients will also be followed with standard neurological exams (every 3 months), however it is hypothesized that, with only 6 months of treatment, no effect of T gel treatment will be observed on clinical disease activity (disability, relapse rate) since this is a less sensitive measure. Further, to determine whether T gel treatment induces desired effects in the immune system, immune responses will be assessed before treatment and during treatment. Results of in vivo (delayed type hypersensitivity) and in vitro (cytokine production) responses will be compared before treatment with those during treatment. Finally, since T gel therapy at this dose of 100 mg/day has been shown to improve sexual function and mood, increase lean body mass and strength, decrease body fat and increase bone mineral density, we will monitor whether these positive effects also occur in men with MS during treatment.

Minimum age: 18 Years. Maximum age: 65 Years. Gender(s): Male.

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.

University of California, Los Angeles, Los Angeles, California 90095, United States

Related publications:

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.

Starting date: April 2002
Ending date: March 2004
Last updated: November 29, 2006