Testosterone Treatment for Multiple Sclerosis

While testosterone (T) has been previously shown to be safe and well tolerated in hypogonadal
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.

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.