Pompe Disease Clinical Trial
Official title:
A Clinical Investigation of the Safety and Efficacy of Clenbuterol on Motor Function in Individuals With Late-onset Pompe Disease and Receiving Enzyme Replacement Therapy
Verified date | June 2019 |
Source | Duke University |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
Funding Source- FDA OOPD
The purpose of this study is to investigate the safety and efficacy of clenbuterol on motor
function in individuals with late-onset Pompe disease (LOPD) who are treated with enzyme
replacement therapy (ERT).
Status | Completed |
Enrollment | 17 |
Est. completion date | September 2, 2016 |
Est. primary completion date | September 2, 2016 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years and older |
Eligibility |
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 ERT 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, arrythmia, cardiomyopathy) 4. Tachycardia 5. History of seizure disorder 6. Hyperthyroidism 7. Pheochromocytoma 8. Pregnancy 9. History of diabetes 10. History of hypersensitivity to beta 2-agonist drugs such as albuterol, levalbuterol (Xopenex), bitolterol (Tornalate), pirbuterol (Maxair), terbutaline, salmeterol (Serevent), 11. Patients on a non-standard schedule for ERT; for example, weekly infusions as opposed to infusions every two weeks. 12. Treatment for asthma in the previous 12 months. 13. 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 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). |
Country | Name | City | State |
---|---|---|---|
United States | Duke University Medical Center | Durham | North Carolina |
Lead Sponsor | Collaborator |
---|---|
Dwight Koeberl, M.D., Ph.D. |
United States,
Kamalakkannan G, Petrilli CM, George I, LaManca J, McLaughlin BT, Shane E, Mancini DM, Maybaum S. Clenbuterol increases lean muscle mass but not endurance in patients with chronic heart failure. J Heart Lung Transplant. 2008 Apr;27(4):457-61. doi: 10.1016/j.healun.2008.01.013. — View Citation
Koeberl DD, Li S, Dai J, Thurberg BL, Bali D, Kishnani PS. ß2 Agonists enhance the efficacy of simultaneous enzyme replacement therapy in murine Pompe disease. Mol Genet Metab. 2012 Feb;105(2):221-7. doi: 10.1016/j.ymgme.2011.11.005. Epub 2011 Nov 11. — View Citation
Koeberl DD, Luo X, Sun B, McVie-Wylie A, Dai J, Li S, Banugaria SG, Chen YT, Bali DS. Enhanced efficacy of enzyme replacement therapy in Pompe disease through mannose-6-phosphate receptor expression in skeletal muscle. Mol Genet Metab. 2011 Jun;103(2):107-12. doi: 10.1016/j.ymgme.2011.02.006. Epub 2011 Feb 13. — View Citation
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Number of Participants With a Change in Creatine Kinase (CK) Reflecting Worsening of Muscle Involvement | Worsening muscle involvement, as defined by >3x increase in CK from baseline that is >2x the upper limit of normal | Any point up to week 52 | |
Primary | Number of Participants With a Change in Aspartate Aminotransferase (AST), Alanine Transaminase (ALT), and Bilirubin Representing Liver Toxicity | Liver toxicity, as defined by a >3x increase in AST or ALT from the respective baseline values and/or an increase in direct, indirect or total bilirubin of >3x the upper limit of normal | Any point up to week 52 | |
Secondary | Change in 6 Minute Walk Test | Assess exercise tolerance in study patients; test administered by physical therapist. Subjects were asked to walk for 6 minutes, unassisted. The distance walked was recorded in meters. | Baseline, week 18 | |
Secondary | Change in 6 Minute Walk Test | Assess exercise tolerance in study patients; test administered by physical therapist. Subjects were asked to walk for 6 minutes, unassisted. The distance walked was recorded in meters. | Baseline, week 52 | |
Secondary | Change in Forced Vital Capacity (FVC) in Pulmonary Function Testing | Forced vital capacity (FVC) is the total amount of air exhaled during the lung function test. | Baseline, Week 18 | |
Secondary | Change in Forced Vital Capacity (FVC) in Pulmonary Function Testing | Forced vital capacity (FVC) is the total amount of air exhaled during the lung function test. | Baseline, Week 52 | |
Secondary | Change in Urinary Glc4 Biomarker | The Glc4 biomarker is measured in urine and correlates with muscle glycogen content. It is a noninvasive measurement that serves as a biomarker for Pompe disease. | Baseline, Week 18 | |
Secondary | Change in Urinary Glc4 Biomarker | Baseline, Week 52 | ||
Secondary | GSGC (Gait, Stairs, Gowers, Arising From a Chair.) | The GSGC is a criterion referenced assessment designed to measure functional status and change in gross motor function over time and, in particular, to measure clinically relevant change. Consists of 4 components: Gait, Climbing Stairs, Gower's Manuever, Arising From a Chair. Lowest score 4 = normal muscle function, highest score 27 = unable to perform motor function tests. | Baseline, Week 18, and Week 52 | |
Secondary | Quick Motor Function Test (QMFT) | The QMFT is a criterion referenced assessment designed to measure functional status and change in gross motor function over time and, in particular, to measure clinically relevant change. Consists of 16 motor function tests. Lowest score 0 = unable to perform motor function tests, highest score 64 = normal muscle function. | Baseline, Week 18, and Week 52 | |
Secondary | Late-Life Function and Disability Instrument (LLFDI) | The Late-Life Function & Disability Instrument (Late-Life FDI) is an evaluative outcome instrument for community-dwelling older adults. Highest score 240 = normal function and no disability, lowest score 0 = low levels of frequency of participating in life tasks. | Baseline, Week 18, Week 52 | |
Secondary | Predicted Maximum Inspiration Pressure (MIP) | MIP is a measurement of inspiratory muscle weakness, including weakness of the diaphragm. MIP is decreased in Pompe disease and reflects weakness of respiratory muscles. | Baseline, Week 18, and Week 52 | |
Secondary | Maximum Expiratory Pressure (MEP) | MEP reflects the strength of the abdominal muscles and other expiratory muscles. | Baseline, Week 18, and Week 52 |
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