Dutasteride to Treat Spinal and Bulbar Muscular Atrophy (SBMA)

• Sponsor: National Institute of Neurological Disorders and Stroke (NINDS) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT00303446
• Collaborator: (none)
• Enrollment: 57
• Location: 1
• Arms: 2
• Duration (Months): 45
• Patients Per Site Per Month: 1.3

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Kennedy's Disease; Spinal and Bulbar Muscular Atrophy	Drug: Dutasteride; Drug: Placebo	Phase 2

Detailed Description

Background:

Spinal and bulbar muscular atrophy (SBMA) or Kennedy's disease is a slowly progressive, X-linked motor neuron disease for which there is currently no treatment. It is caused by a mutation in the androgen receptor that results in a polyglutamine repeat expansion. Recent animal studies have demonstrated that decreasing endogenous androgen levels leads to functional improvement and increased survival. Studies have also shown that high levels of 5 alpha-reductase, the enzyme that converts testosterone to the more potent dihydrotestosterone (DHT), are present in the ventral spinal cord, while low levels of this enzyme are found within skeletal muscle. Thus, by selectively decreasing levels of DHT with dutasteride, a 5 alpha-reductase inhibitor, it is hypothesized that there will be a selective protection of motor neurons, without the adverse effects of reducing the anabolic effects of androgen on muscle.

Objective:

This will be a phase II, double-blind, placebo-controlled trial examining the safety and efficacy of the 5 alpha-reductase inhibitor dutasteride in inhibiting the progression of neurodegeneration in patients with Kennedy's disease. Natural history data will also be obtained from the placebo control arm.

Study Population:

We aim to enroll 50 men with genetically confirmed Kennedy's disease.

Design:

Our objective is to examine the safety and efficacy of dutasteride given at a dose of 0.5 mg a day for 2 years in an outpatient setting. This will be a randomized, double-blind, placebo-controlled trial with 25 subjects in each arm. The subjects will be evaluated neurologically and endocrinologically every 6 months at the NIH Clinical Center. In addition to their clinical visits at the NIH, subjects will also be examined by their primary physician after 3, 9, 15, and 21 months of treatment. The primary objective is to examine the effects of dutasteride on inhibiting or reversing the rate of progression of weakness as measured by quantitative muscle testing. Following informed consent, patients will undergo an initial medical history and physical followed by testing of specific neurological and endocrinological measures over a two-day outpatient visit. Patients will provide blood samples for analysis of hormonal levels and extent of muscle damage every three months. In addition, at the initial, one-year, and two-year follow-up visits patients will have nerve conduction studies as well as quantitative and functional strength evaluation. Each patient will be randomized to the treatment or placebo arm and will be given a 3 month supply of the study drug or a matched placebo at each visit. In between clinic visits, the NIH clinical pharmacy will send an additional 3 month supply to each subject until the subsequent visit.

Outcome Measures:

The primary outcome measure used will be quantitative muscle testing (QMT). Secondary outcome measures include the Adult Myositis Assessment Tool (AMAT), 2-minute walk, a quality of life measure (Medical Outcomes Study 36-item Short Form Version 2, SF-36v2), neurophysiological testing (sensory nerve action potentials, and statistical motor unit number estimation). Changes in hormone levels (testosterone, dihydrotestosterone, androstenedione, estradiol), and creatine kinase levels will also be measured and correlated with changes in strength. Evaluation of disease severity and course as related to CAG repeat length and androgen levels will also be assessed.

Future Directions:

The results of this phase II study will assist us in developing a multi-center, double-blind, placebo-controlled phase III trial. In addition, natural history data will be obtained from the control arm that will be important in future clinical trials of SBMA.

Study Design

• Study Type: Interventional
• Actual Enrollment: 57 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• 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)
• Study Start Date: Mar 1, 2006
• Actual Primary Completion Date: Dec 1, 2009
• Actual Study Completion Date: Dec 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Dutasteride Dutasteride 0.5 mg/day	Drug: Dutasteride; Dutasteride 0.5 mg/day; Other Names: Avodart
Placebo Comparator: Placebo Matched placebo	Drug: Placebo; Matched placebo

Outcome Measures

Primary Outcome Measures

1. Muscle Strength Change From Baseline [0, 12, and 24 months]

   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.

Secondary Outcome Measures

1. Creatine Kinase, Change From Baseline [0, 12, and 24 months]

   Serum creatine kinase was determined in venous blood samples analyzed at the Department of Laboratory Medicine of the NIH Clinical Center.

2. Manual Muscle Testing, Change From Baseline. [0, 12, and 24 months]

   Manual muscle testing was performed using a modified Medical Research Council (MRC) scale (0=worst, 5=best); the average muscle score was based on 22 muscle groups.

3. Adult Myopathy Assessment Tool, Change From Baseline [0, 12, and 24 months]

   The Adult Myopathy Assessment Tool rates physical function and muscle endurance, with higher scores indicating better performance; it includes 7 timed functional tasks and 6 endurance tasks (0=worst, 45=best).

4. Timed 2-minute Walk, Change From Baseline [0, 12, and 24 months]

   The subjects did the 2-minute walk in a 50-foot (15.2-meter) corridor three times, and the average distance was calculated. The subjects were allowed to use an assistive device and rest between the trials.

5. Swallow Score Average, Change From Baseline [0, 12, and 24 months]

   Modified barium swallow studies were done at 0, 12, and 24 months. Twenty-five domains were assessed, and six were chosen for final analysis based on the abnormal findings in subjects evaluated at baseline: vallecular pooling and repeated-swallow, each assessed with thin liquids, purees, and solids (rated 1-4, abnormal to normal).

6. Bulbar Rating Scale, Change From Baseline [0, 12, and 24 months]

   The Bulbar Rating Scale includes eight domains each rated on a 1-4 scale, abnormal to normal. The original 8-32 point scale was transformed to a 0-100% scale to represent the responses as percentages.

7. Sensory Nerve Action Potential Average, Change From Baseline [0, 12, and 24 months]

   Nerve conduction studies were done on four sensory nerves (median, ulnar, radial, sural), and the amplitudes of the evoked responses were averaged. Loss of amplitude indicates impairment of conduction.

8. Median Compound Muscle Action Potential, Change From Baseline [0, 12, and 24 months]

   Nerve conduction studies were done on the median motor nerve, and the compound muscle action potential amplitude was determined. Loss of amplitude indicates impairment of conduction.

9. Peroneal Compound Muscle Action Potential, Change From Baseline [0, 12, and 24 months]

   Nerve conduction studies were done on the peroneal nerve, and the compound muscle action potential amplitude was determined. Loss of amplitude indicates impairment of conduction.

10. Motor Unit Nerve Estimation, Change From Baseline [0, 12, and 24 months]

    Motor unit number estimation (MUNE) was done with a statistical MUNE program, on the abductor pollicis brevis. All subjects were evaluated on the right side unless severe atrophy produced very low compound muscle action potentials; in this case, the left side was investigated or the abductor digiti minimi was substituted. A decrease in MUNE indicates a loss of motor units.

11. Activities of Daily Living, Change From Baseline [0, 12, and 24 months]

    Subjects rated their daily activity with a modified 9-question Activities of Daily Living (ADL) questionnaire (0-4, fully impaired to normal).

12. Medical Outcomes Study 36-item Short Form Version 2 (SF-36v2) Physical Component Summary, Change From Baseline [0, 12, and 24 months]

    Subjects completed the Medical Outcomes Study Short Form Version 2 (SF-36v2), in which they rated their physical quality of life over the preceding 4 weeks. Raw SF-36v2 scores were converted to norm-based scales and component summaries using the scoring code provided by QualityMetric (mean=50, standard deviation (SD)=10).

13. Medical Outcomes Study 36-item Short Form Version 2 (SF-36v2) Mental Component Summary, Percent Change From Baseline [0, 12, and 24 months]

    Subjects completed the Medical Outcomes Study Short Form Version 2 (SF-36v2), in which they rated their mental quality of life over the preceding 4 weeks. Raw SF-36v2 scores were converted to norm-based scales and component summaries using the scoring code provided by QualityMetric (mean=50, standard deviation (SD)=10), and percent change in the norm-based scale was calculated.

14. International Index for Erectile Function (IIEF), Change From Baseline [0, 12, and 24 months]

    Sexual function was rated using the International Index of Erectile Function (IIEF). The total IIEF score (5-75, worst-best) was reported as the percent maximum (0-100%).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	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)

Investigators

• Principal Investigator: Kenneth Fischbeck, M.D., NINDS, NIH

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• NIH Clinical Center Detailed Web Page

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00303446
• Other Study ID Numbers: 060113; 06-N-0113
• First Posted: Mar 16, 2006
• Last Update Posted: Jan 27, 2011
• Last Verified: Jan 1, 2011

• Keywords provided by , ,: Motor Neuron; Androgen Receptor; Polyglutamine; X-Linked; Ligand Dependency; Spinal and Bulbar Muscular Atrophy; SBMA; Kennedy Disease
• Additional relevant MeSH terms: Muscular Atrophy; Bulbo-Spinal Atrophy, X-Linked; Atrophy; Dutasteride

Study Results

Participant Flow

Recruitment Details	57 subjects were evaluated at the National Institutes of Health (NIH) Clinical Center.
Pre-assignment Detail	7 subjects were excluded on the basis of screening blood test abnormalities. 50 subjects were randomized.

Arm/Group Title	Placebo	Dutasteride
Arm/Group Description	Matched placebo, one tablet daily	Dutasteride 500 micrograms, one tablet daily.
Period Title: Overall Study
STARTED	25	25
COMPLETED	23	21
NOT COMPLETED	2	4

Baseline Characteristics

Arm/Group Title	Placebo	Dutasteride	Total
Arm/Group Description	Matched placebo, one tablet daily	Dutasteride 500 micrograms, one tablet daily.	Total of all reporting groups
Overall Participants	25	25	50
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	21 84%	21 84%	42 84%
>=65 years	4 16%	4 16%	8 16%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	53.5 (9.2)	51.9 (10.5)	53.1 (9.5)
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%
Male	25 100%	25 100%	50 100%
Region of Enrollment (participants) [Number]
United States	25 100%	25 100%	50 100%

Outcome Measures

1. Primary Outcome

Title	Muscle Strength Change From Baseline
Description	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.
Time Frame	0, 12, and 24 months

Outcome Measure Data

Analysis Population Description

The participants analyzed were those who were available for analysis at 12 and 24 months.

Arm/Group Title	Placebo	Dutasteride
Arm/Group Description	Matched placebo, one tablet daily	Dutasteride 500 micrograms, one tablet daily.
Measure Participants	23	21
Muscle Strength Change From Baseline at 12 Months	-2.2 (9.4)	3.1 (27.1)
Muscle Strength Change From Baseline at 24 Months	-4.5 (13.5)	1.3 (24.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Dutasteride
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.28
	Comments
	Method	Generalized estimating equation model
	Comments	The analysis includes percent change from baseline at 12 and 24 months.

2. Secondary Outcome

Title	Creatine Kinase, Change From Baseline
Description	Serum creatine kinase was determined in venous blood samples analyzed at the Department of Laboratory Medicine of the NIH Clinical Center.
Time Frame	0, 12, and 24 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Dutasteride
Arm/Group Description	Matched placebo, one tablet daily	Dutasteride 500 micrograms, one tablet daily.
Measure Participants	23	21
Creatine kinase change at 12 months	-36 (360)	-32 (375)
Creatine kinase change at 24 months	-19 (494)	-62 (472)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Dutasteride
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.86
	Comments
	Method	Generalized estimating equation model
	Comments	The analysis includes change from baseline at 12 and 24 months.

3. Secondary Outcome

Title	Manual Muscle Testing, Change From Baseline.
Description	Manual muscle testing was performed using a modified Medical Research Council (MRC) scale (0=worst, 5=best); the average muscle score was based on 22 muscle groups.
Time Frame	0, 12, and 24 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Dutasteride
Arm/Group Description	Matched placebo, one tablet daily	Dutasteride 500 micrograms, one tablet daily.
Measure Participants	23	21
Manual Muscle Testing, Change at 12 months	0.04 (0.7)	-0.25 (0.8)
Manual Muscle Testing, Change at 24 months	0.02 (0.7)	0.01 (0.5)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Dutasteride
	Comments	Comparison of changes from baseline in manual muscle testing results.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.47
	Comments
	Method	Generalized estimating equation model
	Comments	The analysis includes change from baseline at 12 and 24 months.

4. Secondary Outcome

Title	Adult Myopathy Assessment Tool, Change From Baseline
Description	The Adult Myopathy Assessment Tool rates physical function and muscle endurance, with higher scores indicating better performance; it includes 7 timed functional tasks and 6 endurance tasks (0=worst, 45=best).
Time Frame	0, 12, and 24 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Dutasteride
Arm/Group Description	Matched placebo, one tablet daily	Dutasteride 500 micrograms, one tablet daily.
Measure Participants	23	21
Adult Myopathy Assessment Tool, Change at 12 mos.	-2.2 (3.7)	-0.7 (2.4)
Adult Myopathy Assessment Tool, Change at 24 mos.	-2.8 (4.2)	-1.5 (3.9)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Dutasteride
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.13
	Comments
	Method	Generalized estimating equation model
	Comments	The analysis includes change from baseline at 12 and 24 months.

5. Secondary Outcome

Title	Timed 2-minute Walk, Change From Baseline
Description	The subjects did the 2-minute walk in a 50-foot (15.2-meter) corridor three times, and the average distance was calculated. The subjects were allowed to use an assistive device and rest between the trials.
Time Frame	0, 12, and 24 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Dutasteride
Arm/Group Description	Matched placebo, one tablet daily	Dutasteride 500 micrograms, one tablet daily.
Measure Participants	23	21
Timed 2-minute Walk, Change at 12 months	8.1 (29.8)	-0.8 (28.5)
Timed 2-minute Walk, Change at 24 months	2.2 (32.6)	-1.6 (29.6)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Dutasteride
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.46
	Comments
	Method	Generalized estimating equation model
	Comments	The analysis includes change from baseline at 12 and 24 months.

6. Secondary Outcome

Title	Swallow Score Average, Change From Baseline
Description	Modified barium swallow studies were done at 0, 12, and 24 months. Twenty-five domains were assessed, and six were chosen for final analysis based on the abnormal findings in subjects evaluated at baseline: vallecular pooling and repeated-swallow, each assessed with thin liquids, purees, and solids (rated 1-4, abnormal to normal).
Time Frame	0, 12, and 24 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Dutasteride
Arm/Group Description	Matched placebo, one tablet daily	Dutasteride 500 micrograms, one tablet daily.
Measure Participants	23	21
Swallow Score Average, Change at 12 months	-0.25 (0.4)	0.06 (0.6)
Swallow Score Average, Change at 24 months	-0.53 (0.5)	-0.14 (0.5)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Dutasteride
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.11
	Comments
	Method	Generalized estimating equation model
	Comments	The analysis includes change from baseline at 12 and 24 months.

7. Secondary Outcome

Title	Bulbar Rating Scale, Change From Baseline
Description	The Bulbar Rating Scale includes eight domains each rated on a 1-4 scale, abnormal to normal. The original 8-32 point scale was transformed to a 0-100% scale to represent the responses as percentages.
Time Frame	0, 12, and 24 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Dutasteride
Arm/Group Description	Matched placebo, one tablet daily	Dutasteride 500 micrograms, one tablet daily.
Measure Participants	23	21
Bulbar Rating Scale, Change at 12 months	5.7 (6.7)	2.6 (6.8)
Bulbar Rating Scale, Change at 24 months	6.4 (5.8)	3.9 (4.6)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Dutasteride
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.08
	Comments
	Method	Generalized estimating equation model
	Comments	The analysis includes change from baseline at 12 and 24 months.

8. Secondary Outcome

Title	Sensory Nerve Action Potential Average, Change From Baseline
Description	Nerve conduction studies were done on four sensory nerves (median, ulnar, radial, sural), and the amplitudes of the evoked responses were averaged. Loss of amplitude indicates impairment of conduction.
Time Frame	0, 12, and 24 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Dutasteride
Arm/Group Description	Matched placebo, one tablet daily	Dutasteride 500 micrograms, one tablet daily.
Measure Participants	23	21
Sensory Nerve Action Potential, Change at 12 mos.	0 (1)	0 (1)
Sensory Nerve Action Potential, Change at 24 mos.	0 (1)	0 (1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Dutasteride
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.73
	Comments
	Method	Generalized estimating equation model
	Comments	The analysis includes change from baseline at 12 and 24 months.

9. Secondary Outcome

Title	Median Compound Muscle Action Potential, Change From Baseline
Description	Nerve conduction studies were done on the median motor nerve, and the compound muscle action potential amplitude was determined. Loss of amplitude indicates impairment of conduction.
Time Frame	0, 12, and 24 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Dutasteride
Arm/Group Description	Matched placebo, one tablet daily	Dutasteride 500 micrograms, one tablet daily.
Measure Participants	23	21
Median Motor Action Potential, Change at 12 months	0.04 (2.15)	0.52 (2.63)
Median Motor Action Potential, Change at 24 months	-0.24 (1.84)	0.24 (1.89)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Dutasteride
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.37
	Comments
	Method	Generalized estimating equation model
	Comments	The analysis includes change from baseline at 12 and 24 months.

10. Secondary Outcome

Title	Peroneal Compound Muscle Action Potential, Change From Baseline
Description	Nerve conduction studies were done on the peroneal nerve, and the compound muscle action potential amplitude was determined. Loss of amplitude indicates impairment of conduction.
Time Frame	0, 12, and 24 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Dutasteride
Arm/Group Description	Matched placebo, one tablet daily	Dutasteride 500 micrograms, one tablet daily.
Measure Participants	23	21
Peroneal Motor Action Potential, Change at 12 mos.	0.16 (1.07)	0.02 (0.84)
Peroneal Motor Action Potential, Change at 24 mos.	0.15 (1.37)	0.04 (0.81)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Dutasteride
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.65
	Comments
	Method	Generalized estimating equation model
	Comments	The analysis includes change from baseline at 12 and 24 months.

11. Secondary Outcome

Title	Motor Unit Nerve Estimation, Change From Baseline
Description	Motor unit number estimation (MUNE) was done with a statistical MUNE program, on the abductor pollicis brevis. All subjects were evaluated on the right side unless severe atrophy produced very low compound muscle action potentials; in this case, the left side was investigated or the abductor digiti minimi was substituted. A decrease in MUNE indicates a loss of motor units.
Time Frame	0, 12, and 24 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Dutasteride
Arm/Group Description	Matched placebo, one tablet daily	Dutasteride 500 micrograms, one tablet daily.
Measure Participants	23	21
Motor Unit Nerve Estimation, Change at 12 months	-4.2 (18.9)	-4.2 (18.7)
Motor Unit Nerve Estimation, Change at 24 months	-2.2 (23.3)	-2.6 (17.5)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Dutasteride
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.99
	Comments
	Method	Generalized estimating equation model
	Comments	The analysis includes change from baseline at 12 and 24 months.

12. Secondary Outcome

Title	Activities of Daily Living, Change From Baseline
Description	Subjects rated their daily activity with a modified 9-question Activities of Daily Living (ADL) questionnaire (0-4, fully impaired to normal).
Time Frame	0, 12, and 24 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Dutasteride
Arm/Group Description	Matched placebo, one tablet daily	Dutasteride 500 micrograms, one tablet daily.
Measure Participants	23	21
Activities of Daily Living, Change at 12 months	0.4 (2.3)	0.4 (2.8)
Activities of Daily Living, Change at 24 months	1.2 (3.3)	1.1 (4.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Dutasteride
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	1.0
	Comments
	Method	Generalized estimating equation model
	Comments	The analysis includes change from baseline at 12 and 24 months.

13. Secondary Outcome

Title	Medical Outcomes Study 36-item Short Form Version 2 (SF-36v2) Physical Component Summary, Change From Baseline
Description	Subjects completed the Medical Outcomes Study Short Form Version 2 (SF-36v2), in which they rated their physical quality of life over the preceding 4 weeks. Raw SF-36v2 scores were converted to norm-based scales and component summaries using the scoring code provided by QualityMetric (mean=50, standard deviation (SD)=10).
Time Frame	0, 12, and 24 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Dutasteride
Arm/Group Description	Matched placebo, one tablet daily	Dutasteride 500 micrograms, one tablet daily.
Measure Participants	23	21
SF-36v2 Physical Component Sum., Change at 12 mos.	-0.9 (6.5)	2.5 (5.9)
SF-36v2 Physical Component Sum., Change at 24 mos.	-3.6 (8.4)	2.1 (6.1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Dutasteride
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.014
	Comments
	Method	Generalized estimating equation model
	Comments	The analysis includes change from baseline at 12 and 24 months.

14. Secondary Outcome

Title	Medical Outcomes Study 36-item Short Form Version 2 (SF-36v2) Mental Component Summary, Percent Change From Baseline
Description	Subjects completed the Medical Outcomes Study Short Form Version 2 (SF-36v2), in which they rated their mental quality of life over the preceding 4 weeks. Raw SF-36v2 scores were converted to norm-based scales and component summaries using the scoring code provided by QualityMetric (mean=50, standard deviation (SD)=10), and percent change in the norm-based scale was calculated.
Time Frame	0, 12, and 24 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Dutasteride
Arm/Group Description	Matched placebo, one tablet daily	Dutasteride 500 micrograms, one tablet daily.
Measure Participants	23	21
SF-36v2 Mental Component Sum., Change at 12 mos.	0.6 (11.1)	0.1 (7.9)
SF-36v2 Mental Component Sum., Change at 24 mos.	3.3 (9.3)	-3.2 (10.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Dutasteride
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.033
	Comments	Generalized estimating equation model showed a significant interaction between time and treatment; therefore a two sample t-test was used at each time point. P-value is given for comparison at 24 months.
	Method	t-test, 2 sided
	Comments

15. Secondary Outcome

Title	International Index for Erectile Function (IIEF), Change From Baseline
Description	Sexual function was rated using the International Index of Erectile Function (IIEF). The total IIEF score (5-75, worst-best) was reported as the percent maximum (0-100%).
Time Frame	0, 12, and 24 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Dutasteride
Arm/Group Description	Matched placebo, one tablet daily	Dutasteride 500 micrograms, one tablet daily.
Measure Participants	23	21
IIEF, Change at 12 months	-2.4 (10.2)	-2.1 (11.6)
IIEF, Change at 24 months	-0.3 (16.4)	-3.5 (6.9)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Dutasteride
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.61
	Comments
	Method	Generalized estimating equation model
	Comments	The analysis includes change from baseline at 12 and 24 months.

Adverse Events

Time Frame	24 months
Adverse Event Reporting Description	Subjects reported the severity and type of adverse events at each visit.
Arm/Group Title	Placebo		Dutasteride
Arm/Group Description	Matched placebo, one tablet daily		Dutasteride 500 micrograms, one tablet daily.
All Cause Mortality
	Placebo		Dutasteride
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo		Dutasteride
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/25 (8%)		5/25 (20%)
Cardiac disorders
cardiac failure	0/25 (0%)	0	1/25 (4%)	1
Gastrointestinal disorders
gastroenteritis	0/25 (0%)	0	1/25 (4%)	1
Musculoskeletal and connective tissue disorders
fall requiring hospitalization	2/25 (8%)	4	2/25 (8%)	2
Respiratory, thoracic and mediastinal disorders
respiratory failure	0/25 (0%)	0	1/25 (4%)	1
Other (Not Including Serious) Adverse Events
	Placebo		Dutasteride
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	23/25 (92%)		23/25 (92%)
Cardiac disorders
cardiac events	3/25 (12%)	3	1/25 (4%)	1
Endocrine disorders
endocrine	0/25 (0%)	0	2/25 (8%)	2
Gastrointestinal disorders
gastrointestinal	5/25 (20%)	8	7/25 (28%)	26
General disorders
constitutional symptoms	3/25 (12%)	4	6/25 (24%)	14
ear-nose-throat	11/25 (44%)	16	10/25 (40%)	20
hematologic	3/25 (12%)	3	2/25 (8%)	2
musculoskeletal	18/25 (72%)	109	11/25 (44%)	73
genitourinary	1/25 (4%)	2	3/25 (12%)	3
Hepatobiliary disorders
hepatic	0/25 (0%)	0	2/25 (8%)	3
Infections and infestations
infectious	12/25 (48%)	312	14/25 (56%)	26
Nervous system disorders
neurologic	15/25 (60%)	34	15/25 (60%)	39
Skin and subcutaneous tissue disorders
dermatologic	3/25 (12%)	3	4/25 (16%)	6

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.