Trial Outcomes & Findings for Dutasteride to Treat Spinal and Bulbar Muscular Atrophy (SBMA) (NCT NCT00303446)

NCT ID: NCT00303446

Last Updated: 2011-01-27

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 57 participants
• Primary outcome timeframe: 0, 12, and 24 months
• Results posted on: 2011-01-27

Participant Flow

57 subjects were evaluated at the National Institutes of Health (NIH) Clinical Center.

7 subjects were excluded on the basis of screening blood test abnormalities. 50 subjects were randomized.

Participant milestones

Measure	Placebo Matched placebo, one tablet daily	Dutasteride Dutasteride 500 micrograms, one tablet daily.
Overall Study STARTED	25	25
Overall Study COMPLETED	23	21
Overall Study NOT COMPLETED	2	4

Reasons for withdrawal

Measure	Placebo Matched placebo, one tablet daily	Dutasteride Dutasteride 500 micrograms, one tablet daily.
Overall Study Withdrawal by Subject	2	2
Overall Study Death	0	1
Overall Study Physician Decision	0	1

Baseline Characteristics

Dutasteride to Treat Spinal and Bulbar Muscular Atrophy (SBMA)

Baseline characteristics by cohort

Measure	Placebo n=25 Participants Matched placebo, one tablet daily	Dutasteride n=25 Participants Dutasteride 500 micrograms, one tablet daily.	Total n=50 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	21 Participants n=5 Participants	21 Participants n=7 Participants	42 Participants n=5 Participants
Age, Categorical >=65 years	4 Participants n=5 Participants	4 Participants n=7 Participants	8 Participants n=5 Participants
Age Continuous	53.5 years STANDARD_DEVIATION 9.2 • n=5 Participants	51.9 years STANDARD_DEVIATION 10.5 • n=7 Participants	53.1 years STANDARD_DEVIATION 9.5 • n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Sex: Female, Male Male	25 Participants n=5 Participants	25 Participants n=7 Participants	50 Participants n=5 Participants
Region of Enrollment United States	25 participants n=5 Participants	25 participants n=7 Participants	50 participants n=5 Participants

PRIMARY outcome

Timeframe: 0, 12, and 24 months

Population: The participants analyzed were those who were available for analysis at 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.

Outcome measures

Measure	Placebo n=23 Participants Matched placebo, one tablet daily	Dutasteride n=21 Participants Dutasteride 500 micrograms, one tablet daily.
Muscle Strength Change From Baseline Muscle Strength Change From Baseline at 12 Months	-2.2 percent change Standard Deviation 9.4	3.1 percent change Standard Deviation 27.1
Muscle Strength Change From Baseline Muscle Strength Change From Baseline at 24 Months	-4.5 percent change Standard Deviation 13.5	1.3 percent change Standard Deviation 24.2

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Placebo n=23 Participants Matched placebo, one tablet daily	Dutasteride n=21 Participants Dutasteride 500 micrograms, one tablet daily.
Creatine Kinase, Change From Baseline Creatine kinase change at 12 months	-36 Units/liter Standard Deviation 360	-32 Units/liter Standard Deviation 375
Creatine Kinase, Change From Baseline Creatine kinase change at 24 months	-19 Units/liter Standard Deviation 494	-62 Units/liter Standard Deviation 472

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Placebo n=23 Participants Matched placebo, one tablet daily	Dutasteride n=21 Participants Dutasteride 500 micrograms, one tablet daily.
Manual Muscle Testing, Change From Baseline. Manual Muscle Testing, Change at 12 months	0.04 MRC units on a scale Standard Deviation 0.7	-0.25 MRC units on a scale Standard Deviation 0.8
Manual Muscle Testing, Change From Baseline. Manual Muscle Testing, Change at 24 months	0.02 MRC units on a scale Standard Deviation 0.7	0.01 MRC units on a scale Standard Deviation 0.5

SECONDARY outcome

Timeframe: 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).

Outcome measures

Measure	Placebo n=23 Participants Matched placebo, one tablet daily	Dutasteride n=21 Participants Dutasteride 500 micrograms, one tablet daily.
Adult Myopathy Assessment Tool, Change From Baseline Adult Myopathy Assessment Tool, Change at 12 mos.	-2.2 units on a scale Standard Deviation 3.7	-0.7 units on a scale Standard Deviation 2.4
Adult Myopathy Assessment Tool, Change From Baseline Adult Myopathy Assessment Tool, Change at 24 mos.	-2.8 units on a scale Standard Deviation 4.2	-1.5 units on a scale Standard Deviation 3.9

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Placebo n=23 Participants Matched placebo, one tablet daily	Dutasteride n=21 Participants Dutasteride 500 micrograms, one tablet daily.
Timed 2-minute Walk, Change From Baseline Timed 2-minute Walk, Change at 12 months	8.1 meters Standard Deviation 29.8	-0.8 meters Standard Deviation 28.5
Timed 2-minute Walk, Change From Baseline Timed 2-minute Walk, Change at 24 months	2.2 meters Standard Deviation 32.6	-1.6 meters Standard Deviation 29.6

SECONDARY outcome

Timeframe: 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).

Outcome measures

Measure	Placebo n=23 Participants Matched placebo, one tablet daily	Dutasteride n=21 Participants Dutasteride 500 micrograms, one tablet daily.
Swallow Score Average, Change From Baseline Swallow Score Average, Change at 12 months	-0.25 units on a scale Standard Deviation 0.4	0.06 units on a scale Standard Deviation 0.6
Swallow Score Average, Change From Baseline Swallow Score Average, Change at 24 months	-0.53 units on a scale Standard Deviation 0.5	-0.14 units on a scale Standard Deviation 0.5

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Placebo n=23 Participants Matched placebo, one tablet daily	Dutasteride n=21 Participants Dutasteride 500 micrograms, one tablet daily.
Bulbar Rating Scale, Change From Baseline Bulbar Rating Scale, Change at 12 months	5.7 percentage of maximum score Standard Deviation 6.7	2.6 percentage of maximum score Standard Deviation 6.8
Bulbar Rating Scale, Change From Baseline Bulbar Rating Scale, Change at 24 months	6.4 percentage of maximum score Standard Deviation 5.8	3.9 percentage of maximum score Standard Deviation 4.6

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Placebo n=23 Participants Matched placebo, one tablet daily	Dutasteride n=21 Participants Dutasteride 500 micrograms, one tablet daily.
Sensory Nerve Action Potential Average, Change From Baseline Sensory Nerve Action Potential, Change at 12 mos.	0 microVolts Standard Deviation 1	0 microVolts Standard Deviation 1
Sensory Nerve Action Potential Average, Change From Baseline Sensory Nerve Action Potential, Change at 24 mos.	0 microVolts Standard Deviation 1	0 microVolts Standard Deviation 1

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Placebo n=23 Participants Matched placebo, one tablet daily	Dutasteride n=21 Participants Dutasteride 500 micrograms, one tablet daily.
Median Compound Muscle Action Potential, Change From Baseline Median Motor Action Potential, Change at 24 months	-0.24 mVolts Standard Deviation 1.84	0.24 mVolts Standard Deviation 1.89
Median Compound Muscle Action Potential, Change From Baseline Median Motor Action Potential, Change at 12 months	0.04 mVolts Standard Deviation 2.15	0.52 mVolts Standard Deviation 2.63

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Placebo n=23 Participants Matched placebo, one tablet daily	Dutasteride n=21 Participants Dutasteride 500 micrograms, one tablet daily.
Peroneal Compound Muscle Action Potential, Change From Baseline Peroneal Motor Action Potential, Change at 12 mos.	0.16 mVolts Standard Deviation 1.07	0.02 mVolts Standard Deviation 0.84
Peroneal Compound Muscle Action Potential, Change From Baseline Peroneal Motor Action Potential, Change at 24 mos.	0.15 mVolts Standard Deviation 1.37	0.04 mVolts Standard Deviation 0.81

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Placebo n=23 Participants Matched placebo, one tablet daily	Dutasteride n=21 Participants Dutasteride 500 micrograms, one tablet daily.
Motor Unit Nerve Estimation, Change From Baseline Motor Unit Nerve Estimation, Change at 12 months	-4.2 motor unit number Standard Deviation 18.9	-4.2 motor unit number Standard Deviation 18.7
Motor Unit Nerve Estimation, Change From Baseline Motor Unit Nerve Estimation, Change at 24 months	-2.2 motor unit number Standard Deviation 23.3	-2.6 motor unit number Standard Deviation 17.5

SECONDARY outcome

Timeframe: 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).

Outcome measures

Measure	Placebo n=23 Participants Matched placebo, one tablet daily	Dutasteride n=21 Participants Dutasteride 500 micrograms, one tablet daily.
Activities of Daily Living, Change From Baseline Activities of Daily Living, Change at 12 months	0.4 units on a scale Standard Deviation 2.3	0.4 units on a scale Standard Deviation 2.8
Activities of Daily Living, Change From Baseline Activities of Daily Living, Change at 24 months	1.2 units on a scale Standard Deviation 3.3	1.1 units on a scale Standard Deviation 4.2

SECONDARY outcome

Timeframe: 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).

Outcome measures

Measure	Placebo n=23 Participants Matched placebo, one tablet daily	Dutasteride n=21 Participants Dutasteride 500 micrograms, one tablet daily.
Medical Outcomes Study 36-item Short Form Version 2 (SF-36v2) Physical Component Summary, Change From Baseline SF-36v2 Physical Component Sum., Change at 12 mos.	-0.9 percent change Standard Deviation 6.5	2.5 percent change Standard Deviation 5.9
Medical Outcomes Study 36-item Short Form Version 2 (SF-36v2) Physical Component Summary, Change From Baseline SF-36v2 Physical Component Sum., Change at 24 mos.	-3.6 percent change Standard Deviation 8.4	2.1 percent change Standard Deviation 6.1

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Placebo n=23 Participants Matched placebo, one tablet daily	Dutasteride n=21 Participants Dutasteride 500 micrograms, one tablet daily.
Medical Outcomes Study 36-item Short Form Version 2 (SF-36v2) Mental Component Summary, Percent Change From Baseline SF-36v2 Mental Component Sum., Change at 12 mos.	0.6 percent change Standard Deviation 11.1	0.1 percent change Standard Deviation 7.9
Medical Outcomes Study 36-item Short Form Version 2 (SF-36v2) Mental Component Summary, Percent Change From Baseline SF-36v2 Mental Component Sum., Change at 24 mos.	3.3 percent change Standard Deviation 9.3	-3.2 percent change Standard Deviation 10.2

SECONDARY outcome

Timeframe: 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%).

Outcome measures

Measure	Placebo n=23 Participants Matched placebo, one tablet daily	Dutasteride n=21 Participants Dutasteride 500 micrograms, one tablet daily.
International Index for Erectile Function (IIEF), Change From Baseline IIEF, Change at 12 months	-2.4 percent of maximum score Standard Deviation 10.2	-2.1 percent of maximum score Standard Deviation 11.6
International Index for Erectile Function (IIEF), Change From Baseline IIEF, Change at 24 months	-0.3 percent of maximum score Standard Deviation 16.4	-3.5 percent of maximum score Standard Deviation 6.9

Adverse Events

Placebo

Serious events: 2 serious events

Other events: 23 other events

Deaths: 0 deaths

Dutasteride

Serious events: 5 serious events

Other events: 23 other events

Deaths: 0 deaths

Serious adverse events

Measure	Placebo n=25 participants at risk Matched placebo, one tablet daily	Dutasteride n=25 participants at risk Dutasteride 500 micrograms, one tablet daily.
Musculoskeletal and connective tissue disorders fall requiring hospitalization	8.0% 2/25 • Number of events 4 • 24 months Subjects reported the severity and type of adverse events at each visit.	8.0% 2/25 • Number of events 2 • 24 months Subjects reported the severity and type of adverse events at each visit.
Cardiac disorders cardiac failure	0.00% 0/25 • 24 months Subjects reported the severity and type of adverse events at each visit.	4.0% 1/25 • Number of events 1 • 24 months Subjects reported the severity and type of adverse events at each visit.
Gastrointestinal disorders gastroenteritis	0.00% 0/25 • 24 months Subjects reported the severity and type of adverse events at each visit.	4.0% 1/25 • Number of events 1 • 24 months Subjects reported the severity and type of adverse events at each visit.
Respiratory, thoracic and mediastinal disorders respiratory failure	0.00% 0/25 • 24 months Subjects reported the severity and type of adverse events at each visit.	4.0% 1/25 • Number of events 1 • 24 months Subjects reported the severity and type of adverse events at each visit.

Other adverse events

Measure	Placebo n=25 participants at risk Matched placebo, one tablet daily	Dutasteride n=25 participants at risk Dutasteride 500 micrograms, one tablet daily.
Cardiac disorders cardiac events	12.0% 3/25 • Number of events 3 • 24 months Subjects reported the severity and type of adverse events at each visit.	4.0% 1/25 • Number of events 1 • 24 months Subjects reported the severity and type of adverse events at each visit.
General disorders constitutional symptoms	12.0% 3/25 • Number of events 4 • 24 months Subjects reported the severity and type of adverse events at each visit.	24.0% 6/25 • Number of events 14 • 24 months Subjects reported the severity and type of adverse events at each visit.
Skin and subcutaneous tissue disorders dermatologic	12.0% 3/25 • Number of events 3 • 24 months Subjects reported the severity and type of adverse events at each visit.	16.0% 4/25 • Number of events 6 • 24 months Subjects reported the severity and type of adverse events at each visit.
Endocrine disorders endocrine	0.00% 0/25 • 24 months Subjects reported the severity and type of adverse events at each visit.	8.0% 2/25 • Number of events 2 • 24 months Subjects reported the severity and type of adverse events at each visit.
General disorders ear-nose-throat	44.0% 11/25 • Number of events 16 • 24 months Subjects reported the severity and type of adverse events at each visit.	40.0% 10/25 • Number of events 20 • 24 months Subjects reported the severity and type of adverse events at each visit.
Gastrointestinal disorders gastrointestinal	20.0% 5/25 • Number of events 8 • 24 months Subjects reported the severity and type of adverse events at each visit.	28.0% 7/25 • Number of events 26 • 24 months Subjects reported the severity and type of adverse events at each visit.
General disorders hematologic	12.0% 3/25 • Number of events 3 • 24 months Subjects reported the severity and type of adverse events at each visit.	8.0% 2/25 • Number of events 2 • 24 months Subjects reported the severity and type of adverse events at each visit.
Hepatobiliary disorders hepatic	0.00% 0/25 • 24 months Subjects reported the severity and type of adverse events at each visit.	8.0% 2/25 • Number of events 3 • 24 months Subjects reported the severity and type of adverse events at each visit.
Infections and infestations infectious	48.0% 12/25 • Number of events 312 • 24 months Subjects reported the severity and type of adverse events at each visit.	56.0% 14/25 • Number of events 26 • 24 months Subjects reported the severity and type of adverse events at each visit.
General disorders musculoskeletal	72.0% 18/25 • Number of events 109 • 24 months Subjects reported the severity and type of adverse events at each visit.	44.0% 11/25 • Number of events 73 • 24 months Subjects reported the severity and type of adverse events at each visit.
Nervous system disorders neurologic	60.0% 15/25 • Number of events 34 • 24 months Subjects reported the severity and type of adverse events at each visit.	60.0% 15/25 • Number of events 39 • 24 months Subjects reported the severity and type of adverse events at each visit.
General disorders genitourinary	4.0% 1/25 • Number of events 2 • 24 months Subjects reported the severity and type of adverse events at each visit.	12.0% 3/25 • Number of events 3 • 24 months Subjects reported the severity and type of adverse events at each visit.

Additional Information

Kenneth Fischbeck, M.D.

National Institute of Neurological Disorders and Stroke (NINDS), National Institutes of Health (NIH)

Phone: 301-435-9318

Email: kf@ninds.nih.gov

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place