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

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Primary Purpose

Status

Withdrawn

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Clenbuterol

Placebos

About this trial

This is an interventional treatment trial for Pompe Disease (Late-onset) focused on measuring Pompe disease, LOPD, Late-onset Pompe Disease

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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).

Exclusion Criteria:

Continuous invasive ventilation (via tracheostomy or endotracheal tube)
6MWT distance >90% of expected performance (% expected)
FVC >90% of expected (upright).
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)
Tachycardia
History of seizure disorder
Hyperthyroidism
Pheochromocytoma
Pregnancy
History of diabetes
History of hypersensitivity to β2-agonist drugs such as albuterol, levalbuterol (Xopenex), bitolterol (Tornalate), pirbuterol (Maxair), terbutaline, salmeterol (Serevent),
Patients on a non-standard schedule for ERT; for example, weekly infusions as opposed to infusions every two weeks.
Treatment for asthma in the previous 12 months.
Renal insufficiency (elevated serum creatinine).
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.
Anti-rhGAA IgG with sustained titer >1:25.600 for >6 months at time of enrollment.
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).

Sites / Locations

Duke University Medical Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

clenbuterol

placebo

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

Changes in 6 minute walk test (MWT) distance

Secondary Outcome Measures

Changes in pulmonary function tests: forced expiratory volume in 1 second (FEV1)

Changes in pulmonary function tests: forced vital capacity (FVC)

Changes in pulmonary function tests: maximum expiratory pressure (MEP)

Changes in pulmonary function tests: Maximum inspiratory pressure (MIP)

Changes in graded functional test: Gait, Stairs, Gower, Chair (GSCS)

Changes in graded functional test: Quick Motor Function Test (QMFT)

Changes in the concentration of alanine transaminase (ALT) in serum

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

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)

Full Information

NCT ID

NCT04094948

First Posted

September 17, 2019

Last Updated

August 15, 2022

Sponsor

Duke University

1. Study Identification

Unique Protocol Identification Number

NCT04094948

Brief Title

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

2. Study Status

Record Verification Date

August 2022

Overall Recruitment Status

Withdrawn

Why Stopped

hasn't got the funding

Study Start Date

January 1, 2023 (Anticipated)

Primary Completion Date

June 30, 2025 (Anticipated)

Study Completion Date

December 30, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Duke University

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

No

Product Manufactured in and Exported from the U.S.

No

Data Monitoring Committee

Yes

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Pompe Disease (Late-onset)

Keywords

Pompe disease, LOPD, Late-onset Pompe Disease

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

0 (Actual)

8. Arms, Groups, and Interventions

Arm Title

clenbuterol

Arm Type

Experimental

Arm Description

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.

Arm Title

placebo

Arm Type

Placebo Comparator

Arm Description

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.

Intervention Type

Drug

Intervention Name(s)

Clenbuterol

Other Intervention Name(s)

Spiropent

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Placebos

Intervention Description

dextrose-filled capsules

Primary Outcome Measure Information:

Title

Changes in 6 minute walk test (MWT) distance

Time Frame