Pompe Disease (Late-onset)
Conditions
Keywords
Pompe disease, LOPD, Late-onset Pompe Disease
Brief summary
The goals of this study are to determine safety and efficacy with regard to motor function of oral clenbuterol in combination with ERT in subjects with LOPD
Interventions
DRUGClenbuterol
20 mcg spiropent tablets will be overencapsulated (two 20 mcg tablets per capsule)
DRUGPlacebos
dextrose-filled capsules
Sponsors
Duke University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Diagnosis of Pompe disease by blood Acid alpha-glucosidase (GAA) assay and GAA gene sequencing, 2. Age: 18+ years at enrollment, 3. Receiving enzyme replacement therapy (ERT) at a stable dose for \>104 weeks, 4. FVC \>15% of expected (supine). 5. Subjects are capable of giving written consent. 6. Able to walk at least 100 meters on the 6 minute walk test (6MWT) (with assistive devices permitted).
Exclusion criteria
1. Continuous invasive ventilation (via tracheostomy or endotracheal tube) 2. 6MWT distance \>90% of expected performance (% expected) 3. FVC \>90% of expected (upright). 4. Clinically relevant illness within two weeks of enrollment including fever \> 38.2o C, vomiting more than once in 24 hours, seizure, or other symptom deemed contraindicative to new therapy. 5. Chronic heart disease (Myocardial infarction, arrythmia, cardiomyopathy) 6. Tachycardia 7. History of seizure disorder 8. Hyperthyroidism 9. Pheochromocytoma 10. Pregnancy 11. History of diabetes 12. History of hypersensitivity to β2-agonist drugs such as albuterol, levalbuterol (Xopenex), bitolterol (Tornalate), pirbuterol (Maxair), terbutaline, salmeterol (Serevent), 13. Patients on a non-standard schedule for ERT; for example, weekly infusions as opposed to infusions every two weeks. 14. Treatment for asthma in the previous 12 months. 15. Renal insufficiency (elevated serum creatinine). 16. Having started respiratory muscle strength training in the last 6 months prior to study day 1 or having discontinued respiratory muscle strength training in the 6-month period preceding study day 1, or having started respiratory strength training greater than 6 months prior to study day 1 and unwilling to continue for the first year of study participation. 17. Received an investigational drug or participated in another interventional study within 90 days of Study Day 1. 18. Anti-rhGAA IgG with sustained titer \>1:25.600 for \>6 months at time of enrollment. 19. 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 (MAO) 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).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Changes in 6 minute walk test (MWT) distance | Baseline (week 0) through 52 weeks |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Changes in pulmonary function tests: forced vital capacity (FVC) | Baseline (week 0) through 52 weeks | — |
| Changes in pulmonary function tests: maximum expiratory pressure (MEP) | Baseline (week 0) through 52 weeks | — |
| Changes in pulmonary function tests: Maximum inspiratory pressure (MIP) | Baseline (week 0) through 52 weeks | — |
| Changes in graded functional test: Gait, Stairs, Gower, Chair (GSCS) | Baseline (week 0) through 52 weeks | — |
| Changes in pulmonary function tests: forced expiratory volume in 1 second (FEV1) | Baseline (week 0) through 52 weeks | — |
| Changes in the concentration of alanine transaminase (ALT) in serum | Baseline (week 0) through 52 weeks | Avoidance of liver toxicity as defined by a a persistent (sustained \>2 weeks) \>3x increase in aspartate aminotransferase (AST) or alanine aminotransferase (ALT) from the respective baseline values and/or an increase in direct, indirect or total bilirubin of \>3x the upper limit of normal (no liver toxicity has been reported in association with clenbuterol administration and therefore repeat testing should be acceptable) |
| Changes in the concentration of creatine kinase (CK) in serum | Baseline (week 0) through 52 weeks | Avoidance of Worsening muscle involvement (i.e. muscle weakness, cramping, or fatigue) accompanied by a persistent (sustained \>2 weeks) \>3x increase in CK from baseline that is \>2x the upper limit of normal (elevated CK is associated with LOPD and minor elevations of CK have been reported in association with clenbuterol administration, therefore repeat testing should be acceptable). |
| Changes in the concentration of urinary glucose tetramer (Glc4) | Baseline (week 0) through 52 weeks | — |
| Changes in graded functional test: Quick Motor Function Test (QMFT) | Baseline (week 0) through 52 weeks | — |
Countries
United States
Outcome results
None listed