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

Phase 2

Withdrawn

• Conditions: Pompe Disease (Late-onset)
• Interventions: Drug: Placebos; Drug: Clenbuterol

• Registration Number: NCT04094948
• Lead Sponsor: Duke University

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

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2019-09-17
• Study First Submitted QC: 2019-09-17
• Study First Posted: 2019-09-19
• Status Verified: 2022-08
• Last Update Submitted: 2022-08-15
• Last Update Posted: 2022-08-17
• Study Start: 2023-01-01
• Primary Completion: 2025-06-30
• Study Completion: 2025-12-30

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

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).

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
placebo	Placebos	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.
clenbuterol	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.

Primary Outcome Measures

Name	Time	Method
Changes in 6 minute walk test (MWT) distance	Baseline (week 0) through 52 weeks

Secondary Outcome Measures

Name	Time	Method
Changes in pulmonary function tests: forced expiratory volume in 1 second (FEV1)	Baseline (week 0) through 52 weeks
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 graded functional test: Quick Motor Function Test (QMFT)	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

Trial Locations

Locations (1)

Duke University Medical Center; 🇺🇸 Durham, North Carolina, United States