Clinical trial NCT01885936: Safety and Efficacy of Albuterol in Individuals With Late-onset Pompe Disease
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Pompe Disease
Keywords: LOPD
Pompe Disease
Lead sponsor: Duke University
Sponsor class: OTHER
First posted: 2013-06-25
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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.

Primary outcomes:
measure: Number of Participants With Adverse Events.
timeFrame: 52 weeks
Secondary outcomes:
measure: Change in Forced Vital Capacity From Pulmonary Function Tests at 30 Weeks and 52 Weeks.
timeFrame: Baseline, Week 30, and Week 52
measure: Change in 6 Minute Walk Test
timeFrame: Baseline, Week 6, and Week 52
Other outcomes:
Locations:
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
Study officials:
affiliation: Duke University
name: Dwight d Koeberl, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Koeberl DD, Li S, Dai J, Thurberg BL, Bali D, Kishnani PS. beta2 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.
citation: 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.