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

Pompe Disease Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01885936
• Other study ID #: Pro00046020
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: June 2013
• Est. completion date: December 16, 2016

Study information

• Verified date: July 2019
• Source: Duke University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 16
• Est. completion date: December 16, 2016
• Est. primary completion date: December 16, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Glycogen Storage Disease Type II
• Pompe Disease

Intervention

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
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.

Locations

Country	Name	City	State
United States	Duke University Medical Center	Durham	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Duke University

Country where clinical trial is conducted

United States, 

References & Publications (1)

Koeberl DD, Li S, Dai J, Thurberg BL, Bali D, Kishnani PS. ß2 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Adverse Events.	All participants who experienced adverse events.	52 weeks
Secondary	Change in Forced Vital Capacity From Pulmonary Function Tests at 30 Weeks and 52 Weeks.	FVC (forced vital capacity) is the amount of air which can be forcibly exhaled from the lungs after taking the deepest breath possible.	Baseline, Week 30, and Week 52
Secondary	Change in 6 Minute Walk Test	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.	Baseline, Week 6, and Week 52