Dutasteride to Treat Spinal and Bulbar Muscular Atrophy (SBMA) - Full Text View

Sponsored by:	National Institute of Neurological Disorders and Stroke (NINDS)
Information provided by:	National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:	NCT00303446

Purpose

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.

Condition	Intervention	Phase
Kennedy's Disease Spinal and Bulbar Muscular Atrophy	Procedure: Neurological Testing Drug: Dutasteride	Phase II

Genetics Home Reference related topics: spinal and bulbar muscular atrophy

Drug Information available for: Dutasteride

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Parallel Assignment, Efficacy Study
Official Title:	Phase II Clinical Trial to Examine the Efficacy and Safety of Dutasteride in Patients With Kennedy's Disease (Spinal and Bulbar Muscular Atrophy)

Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:

Muscle strength [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Muscle function, quality of life, safety [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	60
Study Start Date:	March 2006

Intervention Details:

N/A

Show Detailed Description

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Male
Accepts Healthy Volunteers:	No

Criteria

INCLUSION CIRTERIA:

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 CYP3A4 inhibitors for over 4 weeks.

Patients with any pre-existing liver disease.

Alkaline phosphatase, GGT, or direct bilirubin greater than 1.5 X the upper limit of normal.

SGOT or SGPT greater than 1.5 X upper limit of normal in subjects with normal CK levels.

Creatinine greater than 1.5 X 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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00303446

Locations

United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, United States, 20892

Sponsors and Collaborators

National Institute of Neurological Disorders and Stroke (NINDS)

More Information

NIH Clinical Center Detailed Web Page This link exits the ClinicalTrials.gov site

Publications:

Kennedy WR, Alter M, Sung JH. Progressive proximal spinal and bulbar muscular atrophy of late onset. A sex-linked recessive trait. Neurology. 1968 Jul;18(7):671-80. No abstract available.

Harding AE, Thomas PK, Baraitser M, Bradbury PG, Morgan-Hughes JA, Ponsford JR. X-linked recessive bulbospinal neuronopathy: a report of ten cases. J Neurol Neurosurg Psychiatry. 1982 Nov;45(11):1012-9.

Olney RK, Aminoff MJ, So YT. Clinical and electrodiagnostic features of X-linked recessive bulbospinal neuronopathy. Neurology. 1991 Jun;41(6):823-8.

Responsible Party:	National Institutes of Health ( Kenneth H. Fischbeck, M.D./National Institute of Neurological Disorders and Stroke )
Study ID Numbers:	060113, 06-N-0113
Study First Received:	March 15, 2006
Last Updated:	January 13, 2009
ClinicalTrials.gov Identifier:	NCT00303446
Health Authority:	United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):

Motor Neuron
Androgen Receptor
Polyglutamine
X-Linked

Ligand Dependency
Spinal and Bulbar Muscalr Atrophy
SBMA
Kennedy Disease

Study placed in the following topic categories:

Dutasteride
Pathological Conditions, Anatomical
Signs and Symptoms
Kennedy disease

Neurologic Manifestations
Atrophy
Muscular Atrophy

Additional relevant MeSH terms:

Neuromuscular Manifestations
Molecular Mechanisms of Pharmacological Action
Nervous System Diseases
Enzyme Inhibitors
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 16, 2009