Clinical trial NCT04094948: Phase II Clinical Trial of Clenbuterol in Adult Patients With Pompe Disease
Official title: Phase II Clinical Trial of Clenbuterol in Adult Patients With Pompe Disease Stably Treated With Enzyme Replacement Therapy
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Pompe Disease (Late-onset)
Keywords: Pompe disease
LOPD
Late-onset Pompe Disease
Lead sponsor: Duke University
Sponsor class: OTHER
First posted: 2019-09-19
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


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).

Primary outcomes:
measure: Changes in 6 minute walk test (MWT) distance
timeFrame: Baseline (week 0) through 52 weeks
Secondary outcomes:
measure: Changes in pulmonary function tests: forced expiratory volume in 1 second (FEV1)
timeFrame: Baseline (week 0) through 52 weeks
measure: Changes in pulmonary function tests: forced vital capacity (FVC)
timeFrame: Baseline (week 0) through 52 weeks
measure: Changes in pulmonary function tests: maximum expiratory pressure (MEP)
timeFrame: Baseline (week 0) through 52 weeks
measure: Changes in pulmonary function tests: Maximum inspiratory pressure (MIP)
timeFrame: Baseline (week 0) through 52 weeks
measure: Changes in graded functional test: Gait, Stairs, Gower, Chair (GSCS)
timeFrame: Baseline (week 0) through 52 weeks
measure: Changes in graded functional test: Quick Motor Function Test (QMFT)
timeFrame: Baseline (week 0) through 52 weeks
measure: Changes in the concentration of alanine transaminase (ALT) in serum
timeFrame: Baseline (week 0) through 52 weeks
measure: Changes in the concentration of creatine kinase (CK) in serum
timeFrame: Baseline (week 0) through 52 weeks
measure: Changes in the concentration of urinary glucose tetramer (Glc4)
timeFrame: Baseline (week 0) through 52 weeks
Other outcomes:
Locations:
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
Study officials:
affiliation: Duke University
name: Dwight Koeberl, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: