Dutasteride to Treat Spinal and Bulbar Muscular Atrophy (SBMA)
Condition: Kennedy's Disease; Spinal and Bulbar Muscular Atrophy
MeSH terms: Muscular Atrophy; Bulbo-Spinal Atrophy, X-Linked; Atrophy
Intervention: Dutasteride; Placebo
Intervention description: Dutasteride 0.5 mg/day; Matched placebo
Intervention MeSH terms: Dutasteride
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 57.0
Sex: Male
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Motor Neuron; Androgen Receptor; Polyglutamine; X-Linked; Ligand Dependency; Spinal and Bulbar Muscular Atrophy; SBMA; Kennedy Disease

Summary:

      This study will determine if the drug dutasteride can improve weakness, mobility,
      functioning, nerve function, and quality of life in patients with spinal and bulbar muscular
      atrophy (SBMA). Patients with this inherited disease have an abnormal androgen receptor
      protein. The male hormones testosterone and dihydrotestosterone (DHT) bind to this abnormal
      receptor, causing damage to nerve cells that innervate muscle and leading to weakness.
      Dutasteride decreases DHT production. Lowering DHT levels may decrease the harmful effects of
      DHT to the nerves and improve strength in people with SBMA.

      Males 18 years of age and older with SBMA who have neurological symptoms and can walk 100
      feet (with or without assistive devices) may be eligible for this study. Candidates are
      screened with a blood test and a review of their medical records and genetic studies.

      Participants undergo the following procedures:

        -  Blood and urine tests, history and physical examination, assessment of muscle strength

        -  Quality-of-life questionnaire

        -  Tests to assess functional abilities, such walking up steps, keeping the head up while
           lying down, and other measures

        -  Nerve conduction study and motor unit number estimation to assess nerve damage. A probe
           placed on the skin delivers small electrical impulses and wires taped to the skin record
           the impulses.

        -  Quantitative muscle testing to measure strength. The subject pushes and pulls levers
           attached to a gauge. Strength is recorded by a computer.

        -  Medication. Participants are divided into two groups. One group is given the study drug,
           dutasteride; the other receives a placebo (sugar pill). All participants take their
           assigned medication once a day for 24 months.

        -  Follow-up evaluations. Every 6 months for 2 years, participants return to NIH to repeat
           the tests described above to determine the effects of the dutasteride. Nerve and
           quantitative muscle testing is not done at the 6- and 18-month visits.

        -  In addition to their follow-up appointments here at the NIH every 6 months, participants
           will also have blood tests and a physical examination performed after 3, 9, 15 and 21
           months of treatment by the patient's local physician.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Genetically confirmed SBMA

          -  Neurological symptoms of SBMA

          -  Ability to ambulate 100 feet with or without the use of assistive devices

          -  Willingness to participate in all aspects of trial design and follow-up

          -  Male sex

        Exclusion Criteria:

          -  Age less than 18 years

          -  Female sex

          -  A history of hypersensitivity to dutasteride or 5 alpha-reductase inhibitors.

          -  Exposure to 5 alpha-reductase inhibitors, anti-androgens, testosterone, or steroids in
             the preceding 6 months

          -  Patients who are taking potent cytochrome P450 3A4 (CYP3A4) inhibitors for over 4
             weeks

          -  Patients with any pre-existing liver disease

          -  Alkaline phosphatase, gamma glutamyl transferase, or direct bilirubin greater than 1.5
             times the upper limit of normal

          -  Alanine aminotransferase or aspartate aminotransferase greater than 1.5 times upper
             limit of normal in subjects with normal creatine kinase levels

          -  Creatinine greater than 1.5 times the upper limit of normal

          -  Platelet count, white blood cell count or hemoglobin below the lower limit of normal

          -  Other clinically significant medical disease that, in the judgment of the
             investigators, would expose the patient to undue risk of harm or prevent the patient
             from completing the study