Safety and Efficacy of Albuterol in Individuals With Late-onset Pompe Disease

• Sponsor: Duke University (Other)
• Overall Status: Completed
• CT.gov ID: NCT01885936
• Collaborator: (none)
• Enrollment: 16
• Location: 1
• Arms: 2
• Duration (Months): 42.5
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

In this study the study team proposes to investigate the efficacy of albuterol on motor function of individuals with Late Onset Pompe Disease (LOPD) who are receiving enzyme replacement therapy, given albuterol was well-tolerated in patients with Late Onset Pompe Disease.

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

Study Design

• Study Type: Interventional
• Actual Enrollment: 16 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Phase 1/2 Double-Blind Study of the Safety and Efficacy of Albuterol on Motor Function in Individuals With Late-onset Pompe Disease Receiving Enzyme Replacement Therapy
• Study Start Date: Jun 1, 2013
• Actual Primary Completion Date: Dec 16, 2016
• Actual Study Completion Date: Dec 16, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Albuterol Initially 4 mg daily for one week, then 4 mg BID per oral daily for the next 5 weeks. If the 4 mg BID per oral is well tolerated, the dose will be increased to 8 mg each morning/4 mg each evening for one week, followed by 8 mg BID per oral for the remainder of the study.	Drug: Albuterol; Initially 4 mg daily for one week, 4 mg BID per oral daily for the next 5 weeks. If the 4 mg BID per oral is well tolerated, the dose will be increased to 8 mg each morning/4 mg each evening for one week, followed by 8 mg BID per oral for the remainder of the study.
Placebo Comparator: Placebo Comparator Initially one capsule daily for one week, then one capsule BID per oral daily for the next 5 weeks. If the one capsule BID per oral is well tolerated, the dose will be increased to two capsules each morning/one capsule each evening for one week, followed by two capsules BID per oral for the remainder of the study.	Drug: Placebo; Initially one capsule daily for one week, then one capsule BID per oral daily for the next 5 weeks. If the one capsule BID per oral is well tolerated, the dose will be increased to two capsules each morning/one capsule each evening for one week, followed by two capsules BID per oral for the remainder of the study.

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Adverse Events. [52 weeks]

   All participants who experienced adverse events.

Secondary Outcome Measures

1. Change in Forced Vital Capacity From Pulmonary Function Tests at 30 Weeks and 52 Weeks. [Baseline, Week 30, and Week 52]

   FVC (forced vital capacity) is the amount of air which can be forcibly exhaled from the lungs after taking the deepest breath possible.

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

   The distance covered over a time of 6 minutes is used as the outcome by which to compare changes in performance capacity. Assessed by physical therapist.

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 enzyme replacement therapy 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 in the past 2 months, arrhythmia, cardiomyopathy).

4. History of seizure disorder.

5. History of diabetes.

6. Hypokalemia.

7. History of hyperthyroidism.

8. Pregnancy.

9. Patients on a non-standard schedule for enzyme replacement therapy; for example, weekly infusions as opposed to infusions every two weeks.

10. Anti-rhGAA antibody titer > 1:100,000

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

12. The use of the following medications:

• 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

• bronchodilators such as albuterol, levalbuterol (Xopenex), bitolterol (Tornalate), pirbuterol (Maxair), terbutaline (Brethine, Bricanyl), salmeterol (Serevent), isoetharine (Bronkometer), metaproterenol (Alupent, Metaprel), or isoproterenol (Isuprel Mistometer) within 12 weeks prior to enrollment.

Contacts and Locations

Locations

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

Sponsors and Collaborators

• Duke University

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

• 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.

• Responsible Party: Duke University
• ClinicalTrials.gov Identifier: NCT01885936
• Other Study ID Numbers: Pro00046020
• First Posted: Jun 25, 2013
• Last Update Posted: Jul 15, 2019
• Last Verified: Jul 1, 2019

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Duke University: LOPD; Pompe Disease
• Additional relevant MeSH terms: Glycogen Storage Disease Type II; Albuterol

Study Results

Participant Flow

Pre-assignment Detail	Three enrolled participants decided to withdraw due to travel difficulties.

Arm/Group Title	Albuterol	Placebo Comparator
Arm/Group Description	Initially 4 mg daily for one week, 4 mg BID (twice a day) per oral for the next 5 weeks. If the 4 mg BID per oral is well tolerated, the dose will be increased to 8 mg each morning/4 mg each evening for one week, followed by 8 mg BID per oral for the remainder of the study.	Placebo administered
Period Title: Overall Study
STARTED	8	5
COMPLETED	7	5
NOT COMPLETED	1	0

Baseline Characteristics

Arm/Group Title	Albuterol	Placebo Comparator	Total
Arm/Group Description	Initially 4 mg daily for one week, 4 mg BID per oral daily for the next 5 weeks. If the 4 mg BID per oral is well tolerated, the dose will be increased to 8 mg each morning/4 mg each evening for one week, followed by 8 mg BID per oral for the remainder of the study.	Placebo administered	Total of all reporting groups
Overall Participants	8	5	13
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	47.3 (9.7)	53.4 (9.9)	49.6 (9.9)
Sex: Female, Male (Count of Participants)
Female	6 75%	4 80%	10 76.9%
Male	2 25%	1 20%	3 23.1%
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 (Count of Participants)
United States	8 100%	5 100%	13 100%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Adverse Events.
Description	All participants who experienced adverse events.
Time Frame	52 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Albuterol	Placebo Comparator
Arm/Group Description	Initially 4 mg daily for one week, 4 mg BID per oral daily for the next 5 weeks. If the 4 mg BID per oral is well tolerated, the dose will be increased to 8 mg each morning/4 mg each evening for one week, followed by 8 mg BID per oral for the remainder of the study.	Placebo administered
Measure Participants	8	5
Count of Participants [Participants]	5 62.5%	5 100%

2. Secondary Outcome

Title	Change in Forced Vital Capacity From Pulmonary Function Tests at 30 Weeks and 52 Weeks.
Description	FVC (forced vital capacity) is the amount of air which can be forcibly exhaled from the lungs after taking the deepest breath possible.
Time Frame	Baseline, Week 30, and Week 52

Outcome Measure Data

Analysis Population Description

One subject dropped out from the albuterol group. Later participants were unblinded and switched to drug before Week 52 under an IRB (Institutional Review Board) approved amendment, and 4 late-enrolled drug and 3 late-enrolled placebo subjects could not be included in the analysis at Week 52.

Arm/Group Title	Albuterol	Placebo Comparator
Arm/Group Description	Initially 4 mg daily for one week, 4 mg BID per oral daily for the next 5 weeks. If the 4 mg BID per oral is well tolerated, the dose will be increased to 8 mg each morning/4 mg each evening for one week, followed by 8 mg BID per oral for the remainder of the study.	Placebo administered
Measure Participants	7	5
Change at 30 Weeks	-0.2 (5.7)	0.4 (7.9)
Change at 52 Weeks	-1.3 (6.2)	3.0 (5.7)

3. Secondary Outcome

Title	Change in 6 Minute Walk Test
Description	The distance covered over a time of 6 minutes is used as the outcome by which to compare changes in performance capacity. Assessed by physical therapist.
Time Frame	Baseline, Week 6, and Week 52

Outcome Measure Data

Analysis Population Description

Early participants were not randomized until 6 weeks; 3 drug and 2 placebo subjects could not be included in the analysis. One drug subject missed the Week 6 visit, and one placebo subject could not perform the 6 minute walk test. Later participants were unblinded before Week 52. Four drug and 3 placebo subjects could not be included at Week 52.

Arm/Group Title	Albuterol	Placebo Comparator
Arm/Group Description	Initially 4 mg daily for one week, 4 mg BID per oral daily for the next 5 weeks. If the 4 mg BID per oral is well tolerated, the dose will be increased to 8 mg each morning/4 mg each evening for one week, followed by 8 mg BID per oral for the remainder of the study.	Placebo administered
Measure Participants	3	2
Change at 6 Weeks	24.0 (10.3)	32.0 (58.1)
Change at 52 Weeks	43.6 (26.0)	13.6 (0.9)

Adverse Events

Time Frame	52 Weeks
Arm/Group Title	Albuterol		Placebo Comparator
Arm/Group Description	Initially 4 mg daily for one week, 4 mg BID per oral daily for the next 5 weeks. If the 4 mg BID per oral is well tolerated, the dose will be increased to 8 mg each morning/4 mg each evening for one week, followed by 8 mg BID per oral for the remainder of the study.		Placebo administered
All Cause Mortality
	Albuterol		Placebo Comparator
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/8 (0%)		0/5 (0%)
Serious Adverse Events
	Albuterol		Placebo Comparator
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/8 (0%)		0/5 (0%)
Other (Not Including Serious) Adverse Events
	Albuterol		Placebo Comparator
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/8 (62.5%)		5/5 (100%)
Cardiac disorders
Ankle edema increase	0/8 (0%)		1/5 (20%)
Hypertension	0/8 (0%)		1/5 (20%)
Palpitations	3/8 (37.5%)		2/5 (40%)
Tachycardia	4/8 (50%)		0/5 (0%)
Ear and labyrinth disorders
Otitis	2/8 (25%)		0/5 (0%)
Eye disorders
Dry eyes	1/8 (12.5%)		0/5 (0%)
Gastrointestinal disorders
Abdominal pain	1/8 (12.5%)		1/5 (20%)
Diarrhea	1/8 (12.5%)		1/5 (20%)
Gastritis	1/8 (12.5%)		0/5 (0%)
General disorders
Chills	0/8 (0%)		1/5 (20%)
Energy decrease	0/8 (0%)		1/5 (20%)
Fall	1/8 (12.5%)		4/5 (80%)
Fatigue	2/8 (25%)		0/5 (0%)
Fever	1/8 (12.5%)		0/5 (0%)
Insomnia	5/8 (62.5%)		1/5 (20%)
Shortness of breath	1/8 (12.5%)		0/5 (0%)
Sneezing	0/8 (0%)		1/5 (20%)
Tremors	2/8 (25%)		0/5 (0%)
Weight gain	1/8 (12.5%)		0/5 (0%)
Weight loss	1/8 (12.5%)		1/5 (20%)
Musculoskeletal and connective tissue disorders
Body aches	0/8 (0%)		2/5 (40%)
Body cramps	1/8 (12.5%)		0/5 (0%)
Chest tightness	1/8 (12.5%)		0/5 (0%)
Foot cramps	3/8 (37.5%)		0/5 (0%)
Hand cramps	1/8 (12.5%)		0/5 (0%)
Jaw cramps	2/8 (25%)		0/5 (0%)
Leg cramps	4/8 (50%)		1/5 (20%)
Throat cramps	1/8 (12.5%)		0/5 (0%)
Nervous system disorders
Brain fog	1/8 (12.5%)		0/5 (0%)
Headache	5/8 (62.5%)		1/5 (20%)
Pain	3/8 (37.5%)		5/5 (100%)
Peripheral neuropathy increase	1/8 (12.5%)		1/5 (20%)
Transient global amnesia	0/8 (0%)		1/5 (20%)
Psychiatric disorders
Anxiety	0/8 (0%)		1/5 (20%)
Renal and urinary disorders
Urination increase	3/8 (37.5%)		0/5 (0%)
Respiratory, thoracic and mediastinal disorders
Cough	1/8 (12.5%)		0/5 (0%)
Dry mucous membranes	0/8 (0%)		1/5 (20%)
Rhinorrhea	1/8 (12.5%)		0/5 (0%)
Sinus infection	0/8 (0%)		1/5 (20%)
Sore throat	0/8 (0%)		2/5 (40%)
Skin and subcutaneous tissue disorders
Rash	1/8 (12.5%)		1/5 (20%)

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.