Trial Outcomes & Findings for Safety and Efficacy of Clenbuterol in Individuals With Late-onset Pompe Disease and Receiving Enzyme Replacement Therapy (NCT NCT01942590)
NCT ID: NCT01942590
Last Updated: 2019-07-02
Results Overview
Worsening muscle involvement, as defined by \>3x increase in CK from baseline that is \>2x the upper limit of normal
Recruitment status
COMPLETED
Study phase
PHASE1/PHASE2
Target enrollment
17 participants
Primary outcome timeframe
Any point up to week 52
Results posted on
2019-07-02
Participant Flow
17 participants signed consent; 13 participants were randomized.
Participant milestones
| Measure |
Clenbuterol
Initially, 40 mcg each morning for one week. Then, increase to 40 mcg BID for the next 5 weeks. If tolerated, will increase to 80 mcg in the morning and 40 mcg in the evening for one week. Then, last dose increase will be 80 mcg BID until week 52.
Clenbuterol
|
Placebo Comparator
Initially, one capsule (placebo) each morning for one week. Then, increase to one capsule BID for the next 5 weeks. If tolerated, will increase to two capsules in the morning and one capsule in the evening for one week. Then, last dose increase to two capsules until week 52.
Placebo
|
|---|---|---|
|
Overall Study
STARTED
|
8
|
5
|
|
Overall Study
COMPLETED
|
7
|
4
|
|
Overall Study
NOT COMPLETED
|
1
|
1
|
Reasons for withdrawal
| Measure |
Clenbuterol
Initially, 40 mcg each morning for one week. Then, increase to 40 mcg BID for the next 5 weeks. If tolerated, will increase to 80 mcg in the morning and 40 mcg in the evening for one week. Then, last dose increase will be 80 mcg BID until week 52.
Clenbuterol
|
Placebo Comparator
Initially, one capsule (placebo) each morning for one week. Then, increase to one capsule BID for the next 5 weeks. If tolerated, will increase to two capsules in the morning and one capsule in the evening for one week. Then, last dose increase to two capsules until week 52.
Placebo
|
|---|---|---|
|
Overall Study
Withdrawal by Subject
|
0
|
1
|
|
Overall Study
Adverse Event
|
1
|
0
|
Baseline Characteristics
Safety and Efficacy of Clenbuterol in Individuals With Late-onset Pompe Disease and Receiving Enzyme Replacement Therapy
Baseline characteristics by cohort
| Measure |
Clenbuterol
n=8 Participants
Initially, one capsule (40 mcg) each morning for one week. Then, increase to 40 mcg BID for the next 5 weeks. If tolerated, will increase to 80 mcg in the morning and 40 mcg in the evening for one week. Then, last dose increase will be 80 mcg BID until week 52.
Clenbuterol
|
Placebo Comparator
n=5 Participants
Initially, one capsule (placebo) each morning for one week. Then, increase to one capsule BID for the next 5 weeks. If tolerated, will increase to two capsules in the morning and one capsule in the evening for one week. Then, last dose increase to two capsules until week 52.
Placebo
|
Total
n=13 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
52 years
n=5 Participants
|
32 years
n=7 Participants
|
51 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
3 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
5 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
8 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
13 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
8 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
13 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
8 participants
n=5 Participants
|
5 participants
n=7 Participants
|
13 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Any point up to week 52Worsening muscle involvement, as defined by \>3x increase in CK from baseline that is \>2x the upper limit of normal
Outcome measures
| Measure |
Clenbuterol
n=8 Participants
Initially, 40 mcg each morning for one week. Then, increase to 40 mcg BID for the next 5 weeks. If tolerated, will increase to 80 mcg in the morning and 40 mcg in the evening for one week. Then, last dose increase will be 80 mcg BID until week 52.
Clenbuterol
|
Placebo Comparator
n=5 Participants
Initially, one capsule (placebo) each morning for one week. Then, increase to one capsule BID for the next 5 weeks. If tolerated, will increase to two capsules in the morning and one capsule in the evening for one week. Then, last dose increase to two capsules until week 52.
Placebo
|
|---|---|---|
|
Number of Participants With a Change in Creatine Kinase (CK) Reflecting Worsening of Muscle Involvement
|
1 participants
|
0 participants
|
PRIMARY outcome
Timeframe: Any point up to week 52Liver toxicity, as defined by a \>3x increase in AST or ALT from the respective baseline values and/or an increase in direct, indirect or total bilirubin of \>3x the upper limit of normal
Outcome measures
| Measure |
Clenbuterol
n=8 Participants
Initially, 40 mcg each morning for one week. Then, increase to 40 mcg BID for the next 5 weeks. If tolerated, will increase to 80 mcg in the morning and 40 mcg in the evening for one week. Then, last dose increase will be 80 mcg BID until week 52.
Clenbuterol
|
Placebo Comparator
n=5 Participants
Initially, one capsule (placebo) each morning for one week. Then, increase to one capsule BID for the next 5 weeks. If tolerated, will increase to two capsules in the morning and one capsule in the evening for one week. Then, last dose increase to two capsules until week 52.
Placebo
|
|---|---|---|
|
Number of Participants With a Change in Aspartate Aminotransferase (AST), Alanine Transaminase (ALT), and Bilirubin Representing Liver Toxicity
|
0 participants
|
0 participants
|
SECONDARY outcome
Timeframe: Baseline, week 18Population: Participants who completed 6 minute walk test
Assess exercise tolerance in study patients; test administered by physical therapist. Subjects were asked to walk for 6 minutes, unassisted. The distance walked was recorded in meters.
Outcome measures
| Measure |
Clenbuterol
n=7 Participants
Initially, 40 mcg each morning for one week. Then, increase to 40 mcg BID for the next 5 weeks. If tolerated, will increase to 80 mcg in the morning and 40 mcg in the evening for one week. Then, last dose increase will be 80 mcg BID until week 52.
Clenbuterol
|
Placebo Comparator
n=4 Participants
Initially, one capsule (placebo) each morning for one week. Then, increase to one capsule BID for the next 5 weeks. If tolerated, will increase to two capsules in the morning and one capsule in the evening for one week. Then, last dose increase to two capsules until week 52.
Placebo
|
|---|---|---|
|
Change in 6 Minute Walk Test
|
18.09 meters
Standard Deviation 24.85
|
6.878 meters
Standard Deviation 76.02
|
SECONDARY outcome
Timeframe: Baseline, week 52Population: Participants who completed 6 minute walk test
Assess exercise tolerance in study patients; test administered by physical therapist. Subjects were asked to walk for 6 minutes, unassisted. The distance walked was recorded in meters.
Outcome measures
| Measure |
Clenbuterol
n=6 Participants
Initially, 40 mcg each morning for one week. Then, increase to 40 mcg BID for the next 5 weeks. If tolerated, will increase to 80 mcg in the morning and 40 mcg in the evening for one week. Then, last dose increase will be 80 mcg BID until week 52.
Clenbuterol
|
Placebo Comparator
n=4 Participants
Initially, one capsule (placebo) each morning for one week. Then, increase to one capsule BID for the next 5 weeks. If tolerated, will increase to two capsules in the morning and one capsule in the evening for one week. Then, last dose increase to two capsules until week 52.
Placebo
|
|---|---|---|
|
Change in 6 Minute Walk Test
|
16.42 meters
Standard Deviation 24.61
|
-18.13 meters
Standard Deviation 40.9
|
SECONDARY outcome
Timeframe: Baseline, Week 18Population: participants who completed FVC testing
Forced vital capacity (FVC) is the total amount of air exhaled during the lung function test.
Outcome measures
| Measure |
Clenbuterol
n=8 Participants
Initially, 40 mcg each morning for one week. Then, increase to 40 mcg BID for the next 5 weeks. If tolerated, will increase to 80 mcg in the morning and 40 mcg in the evening for one week. Then, last dose increase will be 80 mcg BID until week 52.
Clenbuterol
|
Placebo Comparator
n=4 Participants
Initially, one capsule (placebo) each morning for one week. Then, increase to one capsule BID for the next 5 weeks. If tolerated, will increase to two capsules in the morning and one capsule in the evening for one week. Then, last dose increase to two capsules until week 52.
Placebo
|
|---|---|---|
|
Change in Forced Vital Capacity (FVC) in Pulmonary Function Testing
|
1.575 change in FVC measured as % expected
Standard Deviation 5.14
|
2.825 change in FVC measured as % expected
Standard Deviation 11.78
|
SECONDARY outcome
Timeframe: Baseline, Week 52Population: participants who completed FVC testing
Forced vital capacity (FVC) is the total amount of air exhaled during the lung function test.
Outcome measures
| Measure |
Clenbuterol
n=7 Participants
Initially, 40 mcg each morning for one week. Then, increase to 40 mcg BID for the next 5 weeks. If tolerated, will increase to 80 mcg in the morning and 40 mcg in the evening for one week. Then, last dose increase will be 80 mcg BID until week 52.
Clenbuterol
|
Placebo Comparator
n=4 Participants
Initially, one capsule (placebo) each morning for one week. Then, increase to one capsule BID for the next 5 weeks. If tolerated, will increase to two capsules in the morning and one capsule in the evening for one week. Then, last dose increase to two capsules until week 52.
Placebo
|
|---|---|---|
|
Change in Forced Vital Capacity (FVC) in Pulmonary Function Testing
|
-5.738 change in FVC measured as % expected
Standard Deviation 20.04
|
7.775 change in FVC measured as % expected
Standard Deviation 11.98
|
SECONDARY outcome
Timeframe: Baseline, Week 18The Glc4 biomarker is measured in urine and correlates with muscle glycogen content. It is a noninvasive measurement that serves as a biomarker for Pompe disease.
Outcome measures
| Measure |
Clenbuterol
n=3 Participants
Initially, 40 mcg each morning for one week. Then, increase to 40 mcg BID for the next 5 weeks. If tolerated, will increase to 80 mcg in the morning and 40 mcg in the evening for one week. Then, last dose increase will be 80 mcg BID until week 52.
Clenbuterol
|
Placebo Comparator
n=4 Participants
Initially, one capsule (placebo) each morning for one week. Then, increase to one capsule BID for the next 5 weeks. If tolerated, will increase to two capsules in the morning and one capsule in the evening for one week. Then, last dose increase to two capsules until week 52.
Placebo
|
|---|---|---|
|
Change in Urinary Glc4 Biomarker
|
-1.733 mmol/mol CN
Standard Deviation 0.6028
|
0.0667 mmol/mol CN
Standard Deviation 0.666
|
SECONDARY outcome
Timeframe: Baseline, Week 52Population: participants who completed urinary Glc4 biomarker collection
Outcome measures
| Measure |
Clenbuterol
n=6 Participants
Initially, 40 mcg each morning for one week. Then, increase to 40 mcg BID for the next 5 weeks. If tolerated, will increase to 80 mcg in the morning and 40 mcg in the evening for one week. Then, last dose increase will be 80 mcg BID until week 52.
Clenbuterol
|
Placebo Comparator
n=3 Participants
Initially, one capsule (placebo) each morning for one week. Then, increase to one capsule BID for the next 5 weeks. If tolerated, will increase to two capsules in the morning and one capsule in the evening for one week. Then, last dose increase to two capsules until week 52.
Placebo
|
|---|---|---|
|
Change in Urinary Glc4 Biomarker
|
-1.1 mmol/mol CN
Standard Deviation 1.857
|
-1.667 mmol/mol CN
Standard Deviation 2.401
|
SECONDARY outcome
Timeframe: Baseline, Week 18, and Week 52Population: participants who completed GSGC testing
The GSGC is a criterion referenced assessment designed to measure functional status and change in gross motor function over time and, in particular, to measure clinically relevant change. Consists of 4 components: Gait, Climbing Stairs, Gower's Manuever, Arising From a Chair. Lowest score 4 = normal muscle function, highest score 27 = unable to perform motor function tests.
Outcome measures
| Measure |
Clenbuterol
n=7 Participants
Initially, 40 mcg each morning for one week. Then, increase to 40 mcg BID for the next 5 weeks. If tolerated, will increase to 80 mcg in the morning and 40 mcg in the evening for one week. Then, last dose increase will be 80 mcg BID until week 52.
Clenbuterol
|
Placebo Comparator
n=4 Participants
Initially, one capsule (placebo) each morning for one week. Then, increase to one capsule BID for the next 5 weeks. If tolerated, will increase to two capsules in the morning and one capsule in the evening for one week. Then, last dose increase to two capsules until week 52.
Placebo
|
|---|---|---|
|
GSGC (Gait, Stairs, Gowers, Arising From a Chair.)
Baseline
|
17 units on a scale
Standard Deviation 4.69
|
7.5 units on a scale
Standard Deviation 5.07
|
|
GSGC (Gait, Stairs, Gowers, Arising From a Chair.)
Week 18
|
15.14 units on a scale
Standard Deviation 5.61
|
6.5 units on a scale
Standard Deviation 3.7
|
|
GSGC (Gait, Stairs, Gowers, Arising From a Chair.)
Week 52
|
13.8 units on a scale
Standard Deviation 5.6
|
6.5 units on a scale
Standard Deviation 3
|
SECONDARY outcome
Timeframe: Baseline, Week 18, and Week 52The QMFT is a criterion referenced assessment designed to measure functional status and change in gross motor function over time and, in particular, to measure clinically relevant change. Consists of 16 motor function tests. Lowest score 0 = unable to perform motor function tests, highest score 64 = normal muscle function.
Outcome measures
| Measure |
Clenbuterol
n=5 Participants
Initially, 40 mcg each morning for one week. Then, increase to 40 mcg BID for the next 5 weeks. If tolerated, will increase to 80 mcg in the morning and 40 mcg in the evening for one week. Then, last dose increase will be 80 mcg BID until week 52.
Clenbuterol
|
Placebo Comparator
n=4 Participants
Initially, one capsule (placebo) each morning for one week. Then, increase to one capsule BID for the next 5 weeks. If tolerated, will increase to two capsules in the morning and one capsule in the evening for one week. Then, last dose increase to two capsules until week 52.
Placebo
|
|---|---|---|
|
Quick Motor Function Test (QMFT)
Baseline
|
35 units on a scale
Standard Deviation 16.4
|
53.75 units on a scale
Standard Deviation 13.7
|
|
Quick Motor Function Test (QMFT)
Week 18
|
40.6 units on a scale
Standard Deviation 17.97
|
54.75 units on a scale
Standard Deviation 14.08
|
|
Quick Motor Function Test (QMFT)
Week 52
|
46.5 units on a scale
Standard Deviation 15.1
|
56.25 units on a scale
Standard Deviation 14.2
|
SECONDARY outcome
Timeframe: Baseline, Week 18, Week 52Population: Participants who completed LLFDI at the visit. Data was not collected from any participants in the placebo group.
The Late-Life Function \& Disability Instrument (Late-Life FDI) is an evaluative outcome instrument for community-dwelling older adults. Highest score 240 = normal function and no disability, lowest score 0 = low levels of frequency of participating in life tasks.
Outcome measures
| Measure |
Clenbuterol
n=4 Participants
Initially, 40 mcg each morning for one week. Then, increase to 40 mcg BID for the next 5 weeks. If tolerated, will increase to 80 mcg in the morning and 40 mcg in the evening for one week. Then, last dose increase will be 80 mcg BID until week 52.
Clenbuterol
|
Placebo Comparator
Initially, one capsule (placebo) each morning for one week. Then, increase to one capsule BID for the next 5 weeks. If tolerated, will increase to two capsules in the morning and one capsule in the evening for one week. Then, last dose increase to two capsules until week 52.
Placebo
|
|---|---|---|
|
Late-Life Function and Disability Instrument (LLFDI)
Baseline
|
103.75 units on a scale
Standard Deviation 26.81
|
—
|
|
Late-Life Function and Disability Instrument (LLFDI)
Week 18
|
106.7 units on a scale
Standard Deviation 39.3
|
—
|
|
Late-Life Function and Disability Instrument (LLFDI)
Week 52
|
112.5 units on a scale
Standard Deviation 27.4
|
—
|
SECONDARY outcome
Timeframe: Baseline, Week 18, and Week 52Population: Participants who completed the MIP testing
MIP is a measurement of inspiratory muscle weakness, including weakness of the diaphragm. MIP is decreased in Pompe disease and reflects weakness of respiratory muscles.
Outcome measures
| Measure |
Clenbuterol
n=7 Participants
Initially, 40 mcg each morning for one week. Then, increase to 40 mcg BID for the next 5 weeks. If tolerated, will increase to 80 mcg in the morning and 40 mcg in the evening for one week. Then, last dose increase will be 80 mcg BID until week 52.
Clenbuterol
|
Placebo Comparator
n=4 Participants
Initially, one capsule (placebo) each morning for one week. Then, increase to one capsule BID for the next 5 weeks. If tolerated, will increase to two capsules in the morning and one capsule in the evening for one week. Then, last dose increase to two capsules until week 52.
Placebo
|
|---|---|---|
|
Predicted Maximum Inspiration Pressure (MIP)
Baseline
|
56.3 percentage of MIP
Standard Deviation 34.64
|
96.8 percentage of MIP
Standard Deviation 17.23
|
|
Predicted Maximum Inspiration Pressure (MIP)
Week 18
|
47.4 percentage of MIP
Standard Deviation 20.19
|
83.8 percentage of MIP
Standard Deviation 15.13
|
|
Predicted Maximum Inspiration Pressure (MIP)
Week 52
|
68.5 percentage of MIP
Standard Deviation 26.86
|
104.6 percentage of MIP
Standard Deviation 13.9
|
SECONDARY outcome
Timeframe: Baseline, Week 18, and Week 52Population: Participants who completed the MEP testing
MEP reflects the strength of the abdominal muscles and other expiratory muscles.
Outcome measures
| Measure |
Clenbuterol
n=7 Participants
Initially, 40 mcg each morning for one week. Then, increase to 40 mcg BID for the next 5 weeks. If tolerated, will increase to 80 mcg in the morning and 40 mcg in the evening for one week. Then, last dose increase will be 80 mcg BID until week 52.
Clenbuterol
|
Placebo Comparator
n=4 Participants
Initially, one capsule (placebo) each morning for one week. Then, increase to one capsule BID for the next 5 weeks. If tolerated, will increase to two capsules in the morning and one capsule in the evening for one week. Then, last dose increase to two capsules until week 52.
Placebo
|
|---|---|---|
|
Maximum Expiratory Pressure (MEP)
Baseline
|
40.4 percentage of MEP
Standard Deviation 17.5
|
62.8 percentage of MEP
Standard Deviation 14.5
|
|
Maximum Expiratory Pressure (MEP)
Week 18
|
40 percentage of MEP
Standard Deviation 16.8
|
83.3 percentage of MEP
Standard Deviation 30.4
|
|
Maximum Expiratory Pressure (MEP)
Week 52
|
53.9 percentage of MEP
Standard Deviation 7.8
|
49.2 percentage of MEP
Standard Deviation 11.6
|
Adverse Events
Clenbuterol
Serious events: 1 serious events
Other events: 8 other events
Deaths: 0 deaths
Placebo Comparator
Serious events: 0 serious events
Other events: 5 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Clenbuterol
n=8 participants at risk
Initially, one capsule (40 mcg) each morning for one week. Then, increase to 40 mcg BID for the next 5 weeks. If tolerated, will increase to 80 mcg in the morning and 40 mcg in the evening for one week. Then, last dose increase will be 80 mcg BID until week 52.
Clenbuterol
|
Placebo Comparator
n=5 participants at risk
Initially, one capsule (placebo) each morning for one week. Then, increase to one capsule BID for the next 5 weeks. If tolerated, will increase to two capsules in the morning and one capsule in the evening for one week. Then, last dose increase to two capsules until week 52.
Placebo
|
|---|---|---|
|
Musculoskeletal and connective tissue disorders
fall
|
12.5%
1/8 • baseline to 52 week
|
0.00%
0/5 • baseline to 52 week
|
Other adverse events
| Measure |
Clenbuterol
n=8 participants at risk
Initially, one capsule (40 mcg) each morning for one week. Then, increase to 40 mcg BID for the next 5 weeks. If tolerated, will increase to 80 mcg in the morning and 40 mcg in the evening for one week. Then, last dose increase will be 80 mcg BID until week 52.
Clenbuterol
|
Placebo Comparator
n=5 participants at risk
Initially, one capsule (placebo) each morning for one week. Then, increase to one capsule BID for the next 5 weeks. If tolerated, will increase to two capsules in the morning and one capsule in the evening for one week. Then, last dose increase to two capsules until week 52.
Placebo
|
|---|---|---|
|
General disorders
anxiety
|
25.0%
2/8 • baseline to 52 week
|
20.0%
1/5 • baseline to 52 week
|
|
General disorders
decreased appetite
|
25.0%
2/8 • baseline to 52 week
|
0.00%
0/5 • baseline to 52 week
|
|
Musculoskeletal and connective tissue disorders
Elevated creatine kinase (>3x baseline)
|
12.5%
1/8 • baseline to 52 week
|
0.00%
0/5 • baseline to 52 week
|
|
Gastrointestinal disorders
GI upset
|
25.0%
2/8 • baseline to 52 week
|
0.00%
0/5 • baseline to 52 week
|
|
General disorders
weight gain
|
25.0%
2/8 • baseline to 52 week
|
0.00%
0/5 • baseline to 52 week
|
|
Renal and urinary disorders
increased urination frequency
|
37.5%
3/8 • baseline to 52 week
|
0.00%
0/5 • baseline to 52 week
|
|
General disorders
Insomnia
|
62.5%
5/8 • baseline to 52 week
|
40.0%
2/5 • baseline to 52 week
|
|
Musculoskeletal and connective tissue disorders
Muscle spasma
|
50.0%
4/8 • baseline to 52 week
|
20.0%
1/5 • baseline to 52 week
|
|
Cardiac disorders
Palpitations
|
25.0%
2/8 • baseline to 52 week
|
20.0%
1/5 • baseline to 52 week
|
|
General disorders
Tremors
|
50.0%
4/8 • baseline to 52 week
|
0.00%
0/5 • baseline to 52 week
|
Additional Information
Dwight Koeberl, M.D., Ph.D.
Duke University Health System
Phone: 919-684-2036
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place