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

• ClinicalTrials.gov Identifier: NCT01885936
• Recruitment Status: Completed
• First Posted: June 25, 2013
• Results First Posted: February 6, 2018
• Last Update Posted: July 15, 2019
• Sponsor: Duke University
• Information provided by (Responsible Party): Duke University

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 (Clinical Trial)
• 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: June 2013
• Actual Primary Completion Date: December 16, 2016
• Actual Study Completion Date: December 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. [ Time Frame: 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. [ Time Frame: 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 [ Time Frame: 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

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

United States, North Carolina

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

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.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Koeberl DD, Case LE, Desai A, Smith EC, Walters C, Han SO, Thurberg BL, Young SP, Bali D, Kishnani PS. Improved muscle function in a phase I/II clinical trial of albuterol in Pompe disease. Mol Genet Metab. 2020 Feb;129(2):67-72. doi: 10.1016/j.ymgme.2019.12.008. Epub 2019 Dec 10.

• Responsible Party: Duke University
• ClinicalTrials.gov Identifier: NCT01885936
• Other Study ID Numbers: Pro00046020
• First Posted: June 25, 2013
• Results First Posted: February 6, 2018
• Last Update Posted: July 15, 2019
• Last Verified: July 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

Keywords provided by Duke University:

LOPD; Pompe Disease

Additional relevant MeSH terms:

Glycogen Storage Disease Type II; Lysosomal Storage Diseases, Nervous System; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Glycogen Storage Disease; Carbohydrate Metabolism, Inborn Errors; Lysosomal Storage Diseases; Metabolic Diseases; Albuterol; Bronchodilator Agents; Autonomic Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Anti-Asthmatic Agents; Respiratory System Agents; Tocolytic Agents; Reproductive Control Agents; Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; Adrenergic Agonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action