Clinical trial NCT00405353: Testosterone Treatment for Multiple Sclerosis
Official title: Testosterone Treatment for Multiple Sclerosis: A Preliminary Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Multiple Sclerosis
Keywords: multiple sclerosis
testosterone
Lead sponsor: University of California, Los Angeles
Sponsor class: OTHER
Collaborators: name: National Multiple Sclerosis Society
First posted: 2006-11-30
Enrollment: 10
Sex: MALE
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Eligibility 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.

Primary outcomes:
measure: Whole Brain Atrophy Rate
timeFrame: Baseline and 12 months
Secondary outcomes:
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: University of California, Los Angeles
state: California
Study officials:
affiliation: University of California, Los Angeles
name: Rhonda Voskuhl, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.