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

NCT ID: NCT04094948

Last Updated: 2022-08-17

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE2
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-01-01
• Study Completion Date: 2025-12-30

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

Conditions

Pompe Disease (Late-onset)

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

clenbuterol

The initial dose of clenbuterol will be 40 mcg per oral each morning for one week, followed by 40 mcg twice per day (BID) for the next 5 weeks until Week 6. If the 40 mcg BID per oral is well tolerated, the dose will be increased to 80 mcg each morning/40 mcg each evening for one week, followed by 80 mcg BID for the next 5 weeks until the Week 12 visit. If 80 mcg BID is tolerated at Week 12, the subject will continue on that dose until Week 52.

Group Type: EXPERIMENTAL

Clenbuterol

Intervention Type: DRUG

20 mcg spiropent tablets will be overencapsulated (two 20 mcg tablets per capsule)

placebo

Initially, one capsule each morning for one week, followed by one capsule BID for the next 5 weeks until Week 6. If tolerated, the dose will be increased to two capsules each morning and 1 capsule each evening for one week, followed by two capsules BID for the next 5 weeks until the Week 12 visit. If two capsules BID is tolerated at Week 12, the subject will continue on that dose until Week 52.

Group Type: PLACEBO_COMPARATOR

Placebos

Intervention Type: DRUG

dextrose-filled capsules

Interventions

Clenbuterol

20 mcg spiropent tablets will be overencapsulated (two 20 mcg tablets per capsule)

Intervention Type: DRUG

Placebos

dextrose-filled capsules

Intervention Type: DRUG

Other Intervention Names

Spiropent

Eligibility Criteria

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).

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Duke University

OTHER

Sponsor Role: lead

Responsible Party

Dwight Koeberl, M.D., Ph.D.

Professor of Pediatrics

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Dwight Koeberl, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Duke University

Locations

Duke University Medical Center

Durham, North Carolina, United States

Countries

United States

Other Identifiers

Pro00102462

Identifier Type: -

Identifier Source: org_study_id