Pompe Disease
Conditions
Keywords
LOPD, Pompe Disease
Brief summary
In this study the study team proposes to investigate the efficacy of albuterol on motor function of individuals with Late Onset Pompe Disease (LOPD) who are receiving enzyme replacement therapy, given albuterol was well-tolerated in patients with Late Onset Pompe Disease.
Interventions
DRUGAlbuterol
Initially 4 mg daily for one week, 4 mg BID per oral daily for the next 5 weeks. If the 4 mg BID per oral is well tolerated, the dose will be increased to 8 mg each morning/4 mg each evening for one week, followed by 8 mg BID per oral for the remainder of the study.
DRUGPlacebo
Initially one capsule daily for one week, then one capsule BID per oral daily for the next 5 weeks. If the one capsule BID per oral is well tolerated, the dose will be increased to two capsules each morning/one capsule each evening for one week, followed by two capsules BID per oral for the remainder of the study.
Sponsors
Duke University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Diagnosis of Pompe disease by blood acid alpha-glucosidase assay and acid alpha-glucosidase gene sequencing, 2. Age: 18+ years at enrollment. 3. Receiving enzyme replacement therapy at standard dose (20 mg/kg every 2 weeks) for at least 52 weeks. 4. Subjects are capable of giving written consent.
Exclusion criteria
1. Continuous invasive ventilation (via tracheostomy or endotracheal tube). 2. Clinically relevant illness within two weeks of enrollment including fever \> 38.2 C, vomiting more than once in 24 hours, seizure, or other symptom deemed contraindicative to new therapy. 3. Chronic heart disease (Myocardial infarction in the past 2 months, arrhythmia, cardiomyopathy). 4. History of seizure disorder. 5. History of diabetes. 6. Hypokalemia. 7. History of hyperthyroidism. 8. Pregnancy. 9. Patients on a non-standard schedule for enzyme replacement therapy; for example, weekly infusions as opposed to infusions every two weeks. 10. Anti-rhGAA antibody titer \> 1:100,000 11. History of hypersensitivity to Beta 2-agonist drugs such as albuterol, levalbuterol (Xopenex), bitolterol (Tornalate), pirbuterol (Maxair), terbutaline, salmeterol (Serevent).. 12. The use of the following medications: * 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 inhibitors such as isocarboxazid (Marplan), phenelzine (Nardil), rasagiline (Azilect), selegiline (Eldepryl, Emsam), or tranylcypromine (Parnate); or * bronchodilators such as albuterol, levalbuterol (Xopenex), bitolterol (Tornalate), pirbuterol (Maxair), terbutaline (Brethine, Bricanyl), salmeterol (Serevent), isoetharine (Bronkometer), metaproterenol (Alupent, Metaprel), or isoproterenol (Isuprel Mistometer) within 12 weeks prior to enrollment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events. | 52 weeks | All participants who experienced adverse events. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Forced Vital Capacity From Pulmonary Function Tests at 30 Weeks and 52 Weeks. | Baseline, Week 30, and Week 52 | FVC (forced vital capacity) is the amount of air which can be forcibly exhaled from the lungs after taking the deepest breath possible. |
| Change in 6 Minute Walk Test | Baseline, Week 6, and Week 52 | The distance covered over a time of 6 minutes is used as the outcome by which to compare changes in performance capacity. Assessed by physical therapist. |
Countries
United States
Participant flow
Pre-assignment details
Three enrolled participants decided to withdraw due to travel difficulties.
Participants by arm
| Arm | Count |
|---|---|
| Albuterol Initially 4 mg daily for one week, 4 mg BID per oral daily for the next 5 weeks. If the 4 mg BID per oral is well tolerated, the dose will be increased to 8 mg each morning/4 mg each evening for one week, followed by 8 mg BID per oral for the remainder of the study. | 8 |
| Placebo Comparator Placebo administered | 5 |
| Total | 13 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Albuterol | Total | Placebo Comparator |
|---|---|---|---|
| Age, Continuous | 47.3 years STANDARD_DEVIATION 9.7 | 49.6 years STANDARD_DEVIATION 9.9 | 53.4 years STANDARD_DEVIATION 9.9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 8 Participants | 13 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 8 Participants | 13 Participants | 5 Participants |
| Region of Enrollment United States | 8 Participants | 13 Participants | 5 Participants |
| Sex: Female, Male Female | 6 Participants | 10 Participants | 4 Participants |
| Sex: Female, Male Male | 2 Participants | 3 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 8 | 0 / 5 |
| other Total, other adverse events | 5 / 8 | 5 / 5 |
| serious Total, serious adverse events | 0 / 8 | 0 / 5 |
Outcome results
Primary
Number of Participants With Adverse Events.
All participants who experienced adverse events.
Time frame: 52 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Albuterol | Number of Participants With Adverse Events. | 5 Participants |
| Placebo Comparator | Number of Participants With Adverse Events. | 5 Participants |
Secondary
Change in 6 Minute Walk Test
The distance covered over a time of 6 minutes is used as the outcome by which to compare changes in performance capacity. Assessed by physical therapist.
Time frame: Baseline, Week 6, and Week 52
Population: Early participants were not randomized until 6 weeks; 3 drug and 2 placebo subjects could not be included in the analysis. One drug subject missed the Week 6 visit, and one placebo subject could not perform the 6 minute walk test. Later participants were unblinded before Week 52. Four drug and 3 placebo subjects could not be included at Week 52.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Albuterol | Change in 6 Minute Walk Test | Change at 6 Weeks | 24.0 meters | Standard Deviation 10.3 |
| Albuterol | Change in 6 Minute Walk Test | Change at 52 Weeks | 43.6 meters | Standard Deviation 26 |
| Placebo Comparator | Change in 6 Minute Walk Test | Change at 6 Weeks | 32.0 meters | Standard Deviation 58.1 |
| Placebo Comparator | Change in 6 Minute Walk Test | Change at 52 Weeks | 13.6 meters | Standard Deviation 0.9 |
Secondary
Change in Forced Vital Capacity From Pulmonary Function Tests at 30 Weeks and 52 Weeks.
FVC (forced vital capacity) is the amount of air which can be forcibly exhaled from the lungs after taking the deepest breath possible.
Time frame: Baseline, Week 30, and Week 52
Population: One subject dropped out from the albuterol group. Later participants were unblinded and switched to drug before Week 52 under an IRB (Institutional Review Board) approved amendment, and 4 late-enrolled drug and 3 late-enrolled placebo subjects could not be included in the analysis at Week 52.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Albuterol | Change in Forced Vital Capacity From Pulmonary Function Tests at 30 Weeks and 52 Weeks. | Change at 30 Weeks | -0.2 Percent of predicted FVC | Standard Deviation 5.7 |
| Albuterol | Change in Forced Vital Capacity From Pulmonary Function Tests at 30 Weeks and 52 Weeks. | Change at 52 Weeks | -1.3 Percent of predicted FVC | Standard Deviation 6.2 |
| Placebo Comparator | Change in Forced Vital Capacity From Pulmonary Function Tests at 30 Weeks and 52 Weeks. | Change at 30 Weeks | 0.4 Percent of predicted FVC | Standard Deviation 7.9 |
| Placebo Comparator | Change in Forced Vital Capacity From Pulmonary Function Tests at 30 Weeks and 52 Weeks. | Change at 52 Weeks | 3.0 Percent of predicted FVC | Standard Deviation 5.7 |