Dutasteride to Treat Spinal and Bulbar Muscular Atrophy (SBMA)

NCT00303446 | Completed Phase 2 Results DMC

• 2 other identifiers: 06011306-N-0113
• Study Type: interventional
• Target: 57
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Kennedy's Disease; Spinal and Bulbar Muscular Atrophy

Keywords

Motor Neuron; Androgen Receptor; Polyglutamine; X-Linked; Ligand Dependency; Spinal and Bulbar Muscular Atrophy; SBMA; Kennedy Disease

Outcome Measures

Primary Outcomes (1)

• Muscle Strength Change From Baseline

  Quantitative muscle assessment (QMA) was done with a fixed frame dynamometer, a strain gauge tensiometer, and a computer-aided acquisition system. Maximal voluntary isometric muscle contractions were measured twice, the average was calculated, and the results were summed over 22 muscle groups (11 on each side). The total force was scaled for body weight and expressed as percent change from baseline. Measurements were performed at 0, 12, and 24 months. The calculated percent changes at 12 and 24 months are shown.

  0, 12, and 24 months

Secondary Outcomes (14)

• Creatine Kinase, Change From Baseline

  0, 12, and 24 months

• Manual Muscle Testing, Change From Baseline.

  0, 12, and 24 months

• Adult Myopathy Assessment Tool, Change From Baseline

  0, 12, and 24 months

• Timed 2-minute Walk, Change From Baseline

  0, 12, and 24 months

• Swallow Score Average, Change From Baseline

  0, 12, and 24 months

Study Arms (2)

Dutasteride

ACTIVE COMPARATOR

Dutasteride 0.5 mg/day

Drug: Dutasteride

Placebo

PLACEBO COMPARATOR

Matched placebo

Drug: Placebo

Interventions

Dutasteride DRUG

Dutasteride 0.5 mg/day

Also known as: Avodart

Dutasteride

Placebo DRUG

Matched placebo

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• National Institute of Neurological Disorders and Stroke (NINDS): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Rhodes LE, Freeman BK, Auh S, Kokkinis AD, La Pean A, Chen C, Lehky TJ, Shrader JA, Levy EW, Harris-Love M, Di Prospero NA, Fischbeck KH. Clinical features of spinal and bulbar muscular atrophy. Brain. 2009 Dec;132(Pt 12):3242-51. doi: 10.1093/brain/awp258.

  PMID: 19846582 RESULT

• Fernandez-Rhodes LE, Kokkinis AD, White MJ, Watts CA, Auh S, Jeffries NO, Shrader JA, Lehky TJ, Li L, Ryder JE, Levy EW, Solomon BI, Harris-Love MO, La Pean A, Schindler AB, Chen C, Di Prospero NA, Fischbeck KH. Efficacy and safety of dutasteride in patients with spinal and bulbar muscular atrophy: a randomised placebo-controlled trial. Lancet Neurol. 2011 Feb;10(2):140-7. doi: 10.1016/S1474-4422(10)70321-5. Epub 2011 Jan 6.

  PMID: 21216197 RESULT

• Harris-Love MO, Fernandez-Rhodes L, Joe G, Shrader JA, Kokkinis A, La Pean Kirschner A, Auh S, Chen C, Li L, Levy E, Davenport TE, Di Prospero NA, Fischbeck KH. Assessing function and endurance in adults with spinal and bulbar muscular atrophy: validity of the adult myopathy assessment tool. Rehabil Res Pract. 2014;2014:873872. doi: 10.1155/2014/873872. Epub 2014 May 5.

  PMID: 24876969 DERIVED

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Bulbo-Spinal Atrophy, X-Linked

Interventions

Dutasteride

Condition Hierarchy (Ancestors)

Muscular Atrophy, Spinal; Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Motor Neuron Disease; Neuromuscular Diseases; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Azasteroids; Steroids, Heterocyclic; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Results Point of Contact

• Title: Kenneth Fischbeck, M.D.
• Organization: National Institute of Neurological Disorders and Stroke (NINDS), National Institutes of Health (NIH)

kf@ninds.nih.gov

301-435-9318

Study Officials

• Kenneth Fischbeck, M.D.

  NINDS, NIH

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH

Study Record Dates

• First Submitted: March 15, 2006
• First Posted: March 16, 2006
• Study Start: March 1, 2006
• Primary Completion: December 1, 2009
• Study Completion: December 1, 2009
• Last Updated: January 27, 2011
• Results First Posted: June 22, 2010

Record last verified: 2011-01

Locations

US (1)