Phase 2 N=50 Randomized Quadruple-blind Treatment

Dutasteride to Treat Spinal and Bulbar Muscular Atrophy (SBMA)

Kennedy's Disease · Spinal and Bulbar Muscular Atrophy

Bottom Line

View on ClinicalTrials.gov: NCT00303446 ↗

Enrolled (actual)

Serious AEs

14.0%

Results posted

Jun 2010

Primary outcome: Primary: Muscle Strength Change From Baseline — -2.2; 3.1; -4.5; 1.3 percent change — p=0.28

Study Design & Population

Study type: Interventional
Phase: Phase 2
Interventions: Dutasteride (Drug); Placebo (Drug)
Age: Adult, Older Adult · 18+ yrs
Sex: Male
Sponsor: National Institute of Neurological Disorders and Stroke (NINDS)
Primary completion: Dec 2009

Outcome Measures

Outcome	Result	p-value
PRIMARY Muscle Strength Change From Baseline	-2.2; 3.1; -4.5; 1.3	0.28
SECONDARY Creatine Kinase, Change From Baseline	-36; -32; -19; -62	0.86
SECONDARY Manual Muscle Testing, Change From Baseline.	0.04; -0.25; 0.02; 0.01	0.47
SECONDARY Adult Myopathy Assessment Tool, Change From Baseline	-2.2; -0.7; -2.8; -1.5	0.13
SECONDARY Timed 2-minute Walk, Change From Baseline	8.1; -0.8; 2.2; -1.6	0.46
SECONDARY Swallow Score Average, Change From Baseline	-0.25; 0.06; -0.53; -0.14	0.11
SECONDARY Bulbar Rating Scale, Change From Baseline	5.7; 2.6; 6.4; 3.9	0.08
SECONDARY Sensory Nerve Action Potential Average, Change From Baseline	0; 0; 0; 0	0.73
SECONDARY Median Compound Muscle Action Potential, Change From Baseline	0.04; 0.52; -0.24; 0.24	0.37
SECONDARY Peroneal Compound Muscle Action Potential, Change From Baseline	0.16; 0.02; 0.15; 0.04	0.65
SECONDARY Motor Unit Nerve Estimation, Change From Baseline	-4.2; -4.2; -2.2; -2.6	0.99
SECONDARY Activities of Daily Living, Change From Baseline	0.4; 0.4; 1.2; 1.1	1.0
SECONDARY Medical Outcomes Study 36-item Short Form Version 2 (SF-36v2) Physical Component Summary, Change From Baseline	-0.9; 2.5; -3.6; 2.1	0.014 sig
SECONDARY Medical Outcomes Study 36-item Short Form Version 2 (SF-36v2) Mental Component Summary, Percent Change From Baseline	0.6; 0.1; 3.3; -3.2	0.033 sig
SECONDARY International Index for Erectile Function (IIEF), Change From Baseline	-2.4; -2.1; -0.3; -3.5	0.61

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

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT00303446). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.