Safety and Efficacy of Clenbuterol in Individuals With Late-onset Pompe Disease and Receiving Enzyme Replacement Therapy

• Sponsor: Dwight Koeberl, M.D., Ph.D. (Other)
• Overall Status: Completed
• CT.gov ID: NCT01942590
• Collaborator: (none)
• Enrollment: 17
• Location: 1
• Arms: 2
• Duration (Months): 36
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

Funding Source- FDA OOPD

The purpose of this study is to investigate the safety and efficacy of clenbuterol on motor function in individuals with late-onset Pompe disease (LOPD) who are treated with enzyme replacement therapy (ERT).

Condition or Disease	Intervention/Treatment	Phase
Pompe Disease	Drug: Clenbuterol; Drug: Placebo	Phase 1/Phase 2

Detailed Description

This is a 52 week Phase I/II double-blind, randomized, placebo-controlled study of adjunctive clenbuterol in LOPD (Table 2, Section 6). All subjects will be evaluated at Week 0 and Week 6 to establish a baseline for motor function testing. At Week 6, subjects will be randomized 3:2 to clenbuterol or placebo, and evaluated for safety and efficacy during the Week 12 and 18 visits. The Investigational Drug Service will maintain double-blinding by providing either the study drug or placebo (over-encapsulated tablets) directly to subjects. The drug (or placebo) will be initiated at the Week 6 visit in a staged manner (first once daily and later BID), and the dose will be increased at the Week 12 visit in a similarly staged manner to minimize AEs and related attrition. All subjects will return for a final visit after a total of 52 weeks in the study.

In terms of standard of care, the subject will have two clinical visits (charged to the subject and/or the subject's insurance company), one at the initiation of the study drug (baseline) and one at the study completion (52 weeks). Study drug will be attempted to be initiated during the "off week", approximately one week following a dose of ERT, and ERT will continue throughout the duration of the study. Thereafter, study visits will be during the "off week". The 6, 12, and 18 week visits will be research visits (not charged to the subject and/or the subject's insurance company) in order to determine subject's overall health status and measure early signs of motor improvement. The initial dose of clenbuterol will be 40 mcg per oral each morning for one week, followed by 40 mcg BID for the next 5 weeks until the week 12 visit. If the 40 mcg BID per oral is well tolerated, the dose will be increased to 80 mcg each morning/40 mcg each evening for one week, followed by 80 mcg BID for the next 5 weeks until the Week 18 visit. If 80 mcg BID is tolerated at Week 18, the subject will continue on that dose until Week 52.

Compliance will be discussed at the Week 6, Week 12, and Week 18 visits. The subject will have phone visits during Week 1, 7, 13, 36, and 52, and compliance will be discussed then. We will call subjects daily during the first week following initiation of study drug (Week 7) and dosage escalation (Week 13) to support subjects through the early adverse effects of tachyphylaxis that may lead to premature termination. An interim call will occur during Week 36 to monitor compliance. Subjects who admit non-compliance, missing >6 doses of the study drug, will be considered non-compliant and withdrawn from the study. Subjects will be called during Week 1 and Week 52, 3 days following the muscle biopsy. All phone calls will review AEs (Table).

The efficacy of clenbuterol treatment during ERT in patients with LOPD will be evaluated with muscle and pulmonary function testing as the primary endpoints. A secondary endpoint, the urinary Glc4 biomarker, will be monitored when the subjects are evaluated at baseline, week 18 and week 52. The impact of enhanced CI-MPR-mediated uptake of GAA will be analyzed by comparing the muscle function, pulmonary function, and biochemical correction of muscle in subjects with LOPD treated with ERT, both prior to and during simultaneous β2 agonist therapy.

Study Design

• Study Type: Interventional
• Actual Enrollment: 17 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Clinical Investigation of the Safety and Efficacy of Clenbuterol on Motor Function in Individuals With Late-onset Pompe Disease and Receiving Enzyme Replacement Therapy
• Study Start Date: Sep 1, 2013
• Actual Primary Completion Date: Sep 2, 2016
• Actual Study Completion Date: Sep 2, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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.	Drug: Clenbuterol; Other Names: Spiropent
Placebo Comparator: Placebo Comparator Initially, one capsule 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 will be two capsules BID until week 52.	Drug: Placebo; Other Names: Capsule

Outcome Measures

Primary Outcome Measures

1. Number of Participants With a Change in Creatine Kinase (CK) Reflecting Worsening of Muscle Involvement [Any point up to week 52]

   Worsening muscle involvement, as defined by >3x increase in CK from baseline that is >2x the upper limit of normal

2. Number of Participants With a Change in Aspartate Aminotransferase (AST), Alanine Transaminase (ALT), and Bilirubin Representing Liver Toxicity [Any point up to week 52]

   Liver 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

Secondary Outcome Measures

1. Change in 6 Minute Walk Test [Baseline, week 18]

   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.

2. Change in 6 Minute Walk Test [Baseline, week 52]

   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.

3. Change in Forced Vital Capacity (FVC) in Pulmonary Function Testing [Baseline, Week 18]

   Forced vital capacity (FVC) is the total amount of air exhaled during the lung function test.

4. Change in Forced Vital Capacity (FVC) in Pulmonary Function Testing [Baseline, Week 52]

   Forced vital capacity (FVC) is the total amount of air exhaled during the lung function test.

5. Change in Urinary Glc4 Biomarker [Baseline, Week 18]

   The 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.

6. Change in Urinary Glc4 Biomarker [Baseline, Week 52]

7. GSGC (Gait, Stairs, Gowers, Arising From a Chair.) [Baseline, Week 18, and Week 52]

   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.

8. Quick Motor Function Test (QMFT) [Baseline, Week 18, and Week 52]

   The 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.

9. Late-Life Function and Disability Instrument (LLFDI) [Baseline, Week 18, Week 52]

   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.

10. Predicted Maximum Inspiration Pressure (MIP) [Baseline, Week 18, and Week 52]

    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.

11. Maximum Expiratory Pressure (MEP) [Baseline, Week 18, and Week 52]

    MEP reflects the strength of the abdominal muscles and other expiratory muscles.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

1. Diagnosis of Pompe disease by blood acid alpha-glucosidase assay and acid alpha-glucosidase gene sequencing,

2. Age: 18+ years at enrollment,

3. Receiving ERT at standard dose (20 mg/kg every 2 weeks) for at least 52 weeks,

4. Subjects are capable of giving written consent.

Exclusion Criteria:

1. Continuous invasive ventilation (via tracheostomy or endotracheal tube)

2. Clinically relevant illness within two weeks of enrollment including fever > 38.2 C, vomiting more than once in 24 hours, seizure, or other symptom deemed contraindicative to new therapy.

3. Chronic heart disease (Myocardial infarction, arrythmia, cardiomyopathy)

4. Tachycardia

5. History of seizure disorder

6. Hyperthyroidism

7. Pheochromocytoma

8. Pregnancy

9. History of diabetes

10. History of hypersensitivity to beta 2-agonist drugs such as albuterol, levalbuterol (Xopenex), bitolterol (Tornalate), pirbuterol (Maxair), terbutaline, salmeterol (Serevent),

11. Patients on a non-standard schedule for ERT; for example, weekly infusions as opposed to infusions every two weeks.

12. Treatment for asthma in the previous 12 months.

13. The use of the following concommitant meds is prohibited during the study:

• diuretics (water pill);

• digoxin (digitalis, Lanoxin);

• beta-blockers such as atenolol (Tenormin), metoprolol (Lopressor), and propranolol (Inderal);

• tricyclic antidepressants such as amitriptyline (Elavil, Etrafon), doxepin (Sinequan), imipramine (Janimine, Tofranil), and nortriptyline (Pamelor);

• Monoamine oxidase inhibitors such as isocarboxazid (Marplan), phenelzine (Nardil), rasagiline (Azilect), selegiline (Eldepryl, Emsam), or tranylcypromine (Parnate); or

• other bronchodilators such as albuterol, levalbuterol (Xopenex), bitolterol (Tornalate), pirbuterol (Maxair), terbutaline (Brethine, Bricanyl), salmeterol (Serevent), isoetherine (Bronkometer), metaproterenol (Alupent, Metaprel), or isoproterenol (Isuprel Mistometer).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Duke University Medical Center	Durham	North Carolina	United States	27710

Sponsors and Collaborators

• Dwight Koeberl, M.D., Ph.D.

Investigators

• Principal Investigator: Dwight D Koeberl, MD, PhD, Duke University

Study Documents (Full-Text)

None provided.

More Information

Publications

• Kamalakkannan G, Petrilli CM, George I, LaManca J, McLaughlin BT, Shane E, Mancini DM, Maybaum S. Clenbuterol increases lean muscle mass but not endurance in patients with chronic heart failure. J Heart Lung Transplant. 2008 Apr;27(4):457-61. doi: 10.1016/j.healun.2008.01.013.
• Koeberl DD, Li S, Dai J, Thurberg BL, Bali D, Kishnani PS. β2 Agonists enhance the efficacy of simultaneous enzyme replacement therapy in murine Pompe disease. Mol Genet Metab. 2012 Feb;105(2):221-7. doi: 10.1016/j.ymgme.2011.11.005. Epub 2011 Nov 11.
• Koeberl DD, Luo X, Sun B, McVie-Wylie A, Dai J, Li S, Banugaria SG, Chen YT, Bali DS. Enhanced efficacy of enzyme replacement therapy in Pompe disease through mannose-6-phosphate receptor expression in skeletal muscle. Mol Genet Metab. 2011 Jun;103(2):107-12. doi: 10.1016/j.ymgme.2011.02.006. Epub 2011 Feb 13.

• Responsible Party: Dwight Koeberl, M.D., Ph.D., Associate Professor, Duke University
• ClinicalTrials.gov Identifier: NCT01942590
• Other Study ID Numbers: Pro00043680; R01FD004364
• First Posted: Sep 16, 2013
• Last Update Posted: Jul 2, 2019
• Last Verified: Jun 1, 2019

• Keywords provided by Dwight Koeberl, M.D., Ph.D., Associate Professor, Duke University: Pompe disease
• Additional relevant MeSH terms: Glycogen Storage Disease Type II; Clenbuterol

Study Results

Participant Flow

Recruitment Details	17 participants signed consent; 13 participants were randomized.

Arm/Group Title	Clenbuterol	Placebo Comparator
Arm/Group Description	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	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
Period Title: Overall Study
STARTED	8	5
COMPLETED	7	4
NOT COMPLETED	1	1

Baseline Characteristics

Arm/Group Title	Clenbuterol	Placebo Comparator	Total
Arm/Group Description	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	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 of all reporting groups
Overall Participants	8	5	13
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	52	32	51
Sex: Female, Male (Count of Participants)
Female	3 37.5%	3 60%	6 46.2%
Male	5 62.5%	2 40%	7 53.8%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%
Not Hispanic or Latino	8 100%	5 100%	13 100%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	8 100%	5 100%	13 100%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	8 100%	5 100%	13 100%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With a Change in Creatine Kinase (CK) Reflecting Worsening of Muscle Involvement
Description	Worsening muscle involvement, as defined by >3x increase in CK from baseline that is >2x the upper limit of normal
Time Frame	Any point up to week 52

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Clenbuterol	Placebo Comparator
Arm/Group Description	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	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
Measure Participants	8	5
Number [participants]	1 12.5%	0 0%

2. Primary Outcome

Title	Number of Participants With a Change in Aspartate Aminotransferase (AST), Alanine Transaminase (ALT), and Bilirubin Representing Liver Toxicity
Description	Liver 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
Time Frame	Any point up to week 52

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Clenbuterol	Placebo Comparator
Arm/Group Description	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	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
Measure Participants	8	5
Number [participants]	0 0%	0 0%

3. Secondary Outcome

Title	Change in 6 Minute Walk Test
Description	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.
Time Frame	Baseline, week 18

Outcome Measure Data

Analysis Population Description

Participants who completed 6 minute walk test

Arm/Group Title	Clenbuterol	Placebo Comparator
Arm/Group Description	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	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
Measure Participants	7	4
Mean (Standard Deviation) [meters]	18.09 (24.85)	6.878 (76.02)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Clenbuterol
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0512
	Comments
	Method	t-test, 1 sided
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo Comparator
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.434
	Comments
	Method	t-test, 1 sided
	Comments

4. Secondary Outcome

Title	Change in 6 Minute Walk Test
Description	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.
Time Frame	Baseline, week 52

Outcome Measure Data

Analysis Population Description

Participants who completed 6 minute walk test

Arm/Group Title	Clenbuterol	Placebo Comparator
Arm/Group Description	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	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
Measure Participants	6	4
Mean (Standard Deviation) [meters]	16.42 (24.61)	-18.13 (40.9)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Clenbuterol
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0816
	Comments	Paired t test comparing each subject's performance at Week 52 to Baseline
	Method	t-test, 1 sided
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo Comparator
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3318
	Comments	Paired t test comparing each subject's performance at Week 52 to Baseline
	Method	t-test, 1 sided
	Comments

5. Secondary Outcome

Title	Change in Forced Vital Capacity (FVC) in Pulmonary Function Testing
Description	Forced vital capacity (FVC) is the total amount of air exhaled during the lung function test.
Time Frame	Baseline, Week 18

Outcome Measure Data

Analysis Population Description

participants who completed FVC testing

Arm/Group Title	Clenbuterol	Placebo Comparator
Arm/Group Description	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	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
Measure Participants	8	4
Mean (Standard Deviation) [change in FVC measured as % expected]	1.575 (5.14)	2.825 (11.78)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Clenbuterol
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2074
	Comments
	Method	t-test, 1 sided
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo Comparator
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.332
	Comments
	Method	t-test, 1 sided
	Comments

6. Secondary Outcome

Title	Change in Forced Vital Capacity (FVC) in Pulmonary Function Testing
Description	Forced vital capacity (FVC) is the total amount of air exhaled during the lung function test.
Time Frame	Baseline, Week 52

Outcome Measure Data

Analysis Population Description

participants who completed FVC testing

Arm/Group Title	Clenbuterol	Placebo Comparator
Arm/Group Description	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	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
Measure Participants	7	4
Mean (Standard Deviation) [change in FVC measured as % expected]	-5.738 (20.04)	7.775 (11.98)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Clenbuterol
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.233
	Comments	Paired t test comparing each subject's performance at Week 52 to Baseline
	Method	t-test, 1 sided
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo Comparator
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.142
	Comments	Paired t test comparing each subject's performance at Week 52 to Baseline
	Method	t-test, 1 sided
	Comments

7. Secondary Outcome

Title	Change in Urinary Glc4 Biomarker
Description	The 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.
Time Frame	Baseline, Week 18

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Clenbuterol	Placebo Comparator
Arm/Group Description	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	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
Measure Participants	3	4
Mean (Standard Deviation) [mmol/mol CN]	-1.733 (0.6028)	0.0667 (0.666)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Clenbuterol
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.019
	Comments
	Method	t-test, 1 sided
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo Comparator
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.366
	Comments
	Method	t-test, 1 sided
	Comments

8. Secondary Outcome

Title	Change in Urinary Glc4 Biomarker
Time Frame	Baseline, Week 52

Outcome Measure Data

Analysis Population Description

participants who completed urinary Glc4 biomarker collection

Arm/Group Title	Clenbuterol	Placebo Comparator
Arm/Group Description	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	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
Measure Participants	6	3
Mean (Standard Deviation) [mmol/mol CN]	-1.1 (1.857)	-1.667 (2.401)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Clenbuterol
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.161
	Comments
	Method	t-test, 1 sided
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo Comparator
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.43
	Comments
	Method	t-test, 1 sided
	Comments

9. Secondary Outcome

Title	GSGC (Gait, Stairs, Gowers, Arising From a Chair.)
Description	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.
Time Frame	Baseline, Week 18, and Week 52

Outcome Measure Data

Analysis Population Description

participants who completed GSGC testing

Arm/Group Title	Clenbuterol	Placebo Comparator
Arm/Group Description	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	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
Measure Participants	7	4
Baseline	17 (4.69)	7.5 (5.07)
Week 18	15.14 (5.61)	6.5 (3.7)
Week 52	13.8 (5.6)	6.5 (3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Clenbuterol
	Comments	Baseline, week 18
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.01
	Comments
	Method	t-test, 1 sided
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Clenbuterol
	Comments	Baseline, week 52
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.004
	Comments
	Method	t-test, 1 sided
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo Comparator
	Comments	Baseline, week 18
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.154
	Comments
	Method	t-test, 1 sided
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo Comparator
	Comments	Baseline, Week 52
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.211
	Comments
	Method	t-test, 1 sided
	Comments

10. Secondary Outcome

Title	Quick Motor Function Test (QMFT)
Description	The 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.
Time Frame	Baseline, Week 18, and Week 52

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Clenbuterol	Placebo Comparator
Arm/Group Description	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	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
Measure Participants	5	4
Baseline	35 (16.4)	53.75 (13.7)
Week 18	40.6 (17.97)	54.75 (14.08)
Week 52	46.5 (15.1)	56.25 (14.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Clenbuterol
	Comments	Baseline, Week 18
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.006
	Comments
	Method	t-test, 1 sided
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Clenbuterol
	Comments	Baseline, Week 52
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.007
	Comments
	Method	t-test, 1 sided
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo Comparator
	Comments	Baseline, Week 18
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.297
	Comments
	Method	t-test, 1 sided
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo Comparator
	Comments	Baseline, Week 52
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.196
	Comments
	Method	t-test, 1 sided
	Comments

11. Secondary Outcome

Title	Late-Life Function and Disability Instrument (LLFDI)
Description	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.
Time Frame	Baseline, Week 18, Week 52

Outcome Measure Data

Analysis Population Description

Participants who completed LLFDI at the visit. Data was not collected from any participants in the placebo group.

Arm/Group Title	Clenbuterol	Placebo Comparator
Arm/Group Description	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	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
Measure Participants	4	0
Baseline	103.75 (26.81)
Week 18	106.7 (39.3)
Week 52	112.5 (27.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Clenbuterol
	Comments	Baseline Week 18
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3639
	Comments
	Method	t-test, 1 sided
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Clenbuterol
	Comments	Baseline, Week 52
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0371
	Comments
	Method	t-test, 1 sided
	Comments

12. Secondary Outcome

Title	Predicted Maximum Inspiration Pressure (MIP)
Description	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.
Time Frame	Baseline, Week 18, and Week 52

Outcome Measure Data

Analysis Population Description

Participants who completed the MIP testing

Arm/Group Title	Clenbuterol	Placebo Comparator
Arm/Group Description	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	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
Measure Participants	7	4
Baseline	56.3 (34.64)	96.8 (17.23)
Week 18	47.4 (20.19)	83.8 (15.13)
Week 52	68.5 (26.86)	104.6 (13.9)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Clenbuterol
	Comments	Baseline, Week 18
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.268
	Comments
	Method	t-test, 1 sided
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Clenbuterol
	Comments	Baseline, Week 52
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0036
	Comments
	Method	t-test, 1 sided
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo Comparator
	Comments	Baseline, Week 18
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.286
	Comments
	Method	t-test, 1 sided
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo Comparator
	Comments	Baseline, Week 52
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.279
	Comments
	Method	t-test, 1 sided
	Comments

13. Secondary Outcome

Title	Maximum Expiratory Pressure (MEP)
Description	MEP reflects the strength of the abdominal muscles and other expiratory muscles.
Time Frame	Baseline, Week 18, and Week 52

Outcome Measure Data

Analysis Population Description

Participants who completed the MEP testing

Arm/Group Title	Clenbuterol	Placebo Comparator
Arm/Group Description	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	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
Measure Participants	7	4
Baseline	40.4 (17.5)	62.8 (14.5)
Week 18	40 (16.8)	83.3 (30.4)
Week 52	53.9 (7.8)	49.2 (11.6)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Clenbuterol
	Comments	Baseline, Week 18
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.479
	Comments
	Method	t-test, 1 sided
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Clenbuterol
	Comments	Baseline, Week 52
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.059
	Comments
	Method	t-test, 1 sided
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo Comparator
	Comments	Baseline, Week 18
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.152
	Comments
	Method	t-test, 1 sided
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo Comparator
	Comments	Baseline, Week 52
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.118
	Comments
	Method	t-test, 1 sided
	Comments

Adverse Events

Time Frame	baseline to 52 week
Arm/Group Title	Clenbuterol		Placebo Comparator
Arm/Group Description	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		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
All Cause Mortality
	Clenbuterol		Placebo Comparator
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/8 (0%)		0/5 (0%)
Serious Adverse Events
	Clenbuterol		Placebo Comparator
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/8 (12.5%)		0/5 (0%)
Musculoskeletal and connective tissue disorders
fall	1/8 (12.5%)		0/5 (0%)
Other (Not Including Serious) Adverse Events
	Clenbuterol		Placebo Comparator
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/8 (100%)		5/5 (100%)
Cardiac disorders
Palpitations	2/8 (25%)		1/5 (20%)
Gastrointestinal disorders
GI upset	2/8 (25%)		0/5 (0%)
General disorders
anxiety	2/8 (25%)		1/5 (20%)
decreased appetite	2/8 (25%)		0/5 (0%)
weight gain	2/8 (25%)		0/5 (0%)
Insomnia	5/8 (62.5%)		2/5 (40%)
Tremors	4/8 (50%)		0/5 (0%)
Musculoskeletal and connective tissue disorders
Elevated creatine kinase (>3x baseline)	1/8 (12.5%)		0/5 (0%)
Muscle spasma	4/8 (50%)		1/5 (20%)
Renal and urinary disorders
increased urination frequency	3/8 (37.5%)		0/5 (0%)

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.