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

Prior treatment

• Treatment for asthma in the previous 12 months.
• 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.
• Received an investigational drug or participated in another interventional study within 90 days of Study Day 1.
• 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).

Other illness

• 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.
• Chronic heart disease (Myocardial infarction, arrythmia, cardiomyopathy)
• History of seizure disorder
• History of diabetes
• History of hypersensitivity to β2-agonist drugs such as albuterol, levalbuterol (Xopenex), bitolterol (Tornalate), pirbuterol (Maxair), terbutaline, salmeterol (Serevent),

Lab values

• Renal insufficiency (elevated serum creatinine).

Other

• Continuous invasive ventilation (via tracheostomy or endotracheal tube)
• 6MWT distance >90% of expected performance (% expected)
• FVC >90% of expected (upright).
• Tachycardia
• Hyperthyroidism
• Pheochromocytoma
• Pregnancy
• Patients on a non-standard schedule for ERT; for example, weekly infusions as opposed to infusions every two weeks.
• Anti-rhGAA IgG with sustained titer >1:25.600 for >6 months at time of enrollment.

• Diagnosis of Pompe disease by blood Acid alpha-glucosidase (GAA) assay and GAA gene sequencing,
• Age: 18+ years at enrollment,
• Receiving enzyme replacement therapy (ERT) at a stable dose for >104 weeks,
• FVC >15% of expected (supine).
• Subjects are capable of giving written consent.
• Able to walk at least 100 meters on the 6 minute walk test (6MWT) (with assistive devices permitted).