Phase II Clinical Trial of Clenbuterol in Adult Patients With Pompe Disease

Phase II Clinical Trial of Clenbuterol in Adult Patients With Pompe Disease Stably Treated With Enzyme Replacement Therapy

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

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).