Cardiopulmonary Exercise Test to Quantify Enzyme Replacement Response in Pediatric Pompe Disease

Introduction: Enzyme replacement therapy (ERT) with Myozyme improved the prospect of Pompe disease patients. Our aim was to evaluate ERT acute effect on exercise capacity in pediatric Pompe patients.

Methods: Pompe patients (10-19 years) were evaluated before and two days after ERT using cardiopulmonary exercise testing (CPET), six minutes walking test (6MWT) and motor function test (GMFM-88).

Study Overview

• Status: Completed
• Conditions: Enzyme Replacement Therapy in Pompe Disease

Detailed Description

Pompe disease is an inherited autosomal recessive glycogen storage disease caused by partial or total deficiency of acid α-glucosidase (GAA), resulting in the accumulation of glycogen in the lysosomes of skeletal muscles, heart, liver and other tissues. There is an inverse correlation between the amount of residual GAA activity and disease severity. The clinical phenotype varies with regard to age of onset, organ involvement, and severity of progression. In 2006, enzyme replacement therapy (ERT) with recombinant human GAA (Genzyme Corporation, Cambridge MA, USA) was approved and, since then, decisive modification of the course of the disease has been reported. Clinical studies in infants showed that ERT led to improvement in cardiac, respiratory and skeletal muscle functions, with achievement of independent walking, higher levels of physical activity, and survival beyond infancy.

Exercise capacity significantly affects Pompe patients' clinical picture and quality of life [5]. However, data on the effects of ERT on physiological variables related to exercise capacity is scarce. Cardiopulmonary exercise testing (CPET) is a well-known procedure to assess exercise capacity in adults and children in healthy and chronic conditions. Little is known regarding exercise capacity in the pediatric Pompe population. Our aim was to evaluate the acute effect of ERT on exercise capacity and different physiological variables in pediatric Pompe patients.

Patients were evaluated before and two days after ERT (20mg/kg/EOW). Each evaluation included CPET, pulmonary function tests, 6MWT and GMFM-88. All tests were carried out by the same experienced physician, exercise physiologist, and physiotherapist.

Visit 1: Patients arrived at that hospital at 7:00 am, vital signs were collected and a complete neuromuscular evaluation was carried out (gross motor function measure score sheet (GMFM-88), 6MWT, pre-CPET questionnaire (demographics, physical activity level, risk assessment, asthma/atopy/smoking history, family history), pulmonary function tests and CPET. Following the evaluation, at approximately 9 am, the patient started infusion of ERT.

Visit 2: Two days following visit 1, the patient arrived at the hospital at 2:00 pm, vital signs were assessed and GMFM-88, 6MWT, pulmonary function tests, and CPET were performed.

• Study Type: Observational
• Enrollment (Actual): 5

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 8 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Pediatric Pompe patients diagnosed by a deficiency of acid alpha-glucosidase enzyme activity in dry blood spot and/or lymphocytes, followed by the study of the disease-causing mutations using DNA analysis of the GAA gene. Age ≥8 y/o, ERT ≥1 year, capable of cycling on a stationary bicycle.

Description

Inclusion Criteria:

• Pompe disease diagnosed by a deficiency of acid alpha-glucosidase enzyme activity in dry blood spot and/or lymphocytes, followed by the study of the disease-causing mutations using DNA analysis of the GAA gene
• Age ≥8 y/o
• ERT ≥1 year
• Capable of cycling on a stationary bicycle.

Exclusion Criteria:

• Invasive ventilation
• Continuous ventilation and/or continuous oxygen supplementation to maintain oxygen saturation >90%
• Acute illness on visit day or one day prior.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Pediatric Pompe patients; Visit 1: Patients arrived at that hospital at 7:00 am, vital signs were collected and a complete neuromuscular evaluation was carried out (gross motor function measure score sheet (GMFM-88), 6MWT, pre-CPET questionnaire (demographics, physical activity level, risk assessment, asthma/atopy/smoking history, family history), pulmonary function tests and CPET. Following the evaluation, at approximately 9 am, the patient started infusion of ERT. Visit 2: Two days following visit 1, the patient arrived at the hospital at 2:00 pm, vital signs were assessed and GMFM-88, 6MWT, pulmonary function tests, and CPET were performed.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in oxygen Uptake	Change in mount of oxygen consumed per amount of time measured during 15 minutes of an exercise test.	3 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
6 Minute walk test	The distance an individual walked in 6 minutes.	3 days
Gross motor function measure score sheet (GMFM-88)	The patient is evaluated in the active performance of 88 physical tasks and the scoring range for each task ranges from 0=does not initiate, 1=initiates, 2=partially completes, 3=completes, NT=not tested. The total score is the sum of all tasks divided to the maximal potential score in percentage. Evaluation time ~ 30 minutes.	3 days
Spirometry	Pulmonary function as assessed by spirometry. Evaluation time - 5 minutes.	3 days.

Collaborators and Investigators

• Sponsor: Rambam Health Care Campus
• Investigators: Principal Investigator: Lea Bentur, Prof., Rambam Health Care Campus

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2014
• Primary Completion (Actual): April 30, 2014
• Study Completion (Actual): March 30, 2017

Study Registration Dates

• First Submitted: April 30, 2017
• First Submitted That Met QC Criteria: May 7, 2017
• First Posted (Actual): May 10, 2017

Study Record Updates

• Last Update Posted (Actual): May 16, 2017
• Last Update Submitted That Met QC Criteria: May 14, 2017
• Last Verified: May 1, 2017

More Information

Terms related to this study

• Keywords: exercise capacity; cardiopulmonary exercise testing; pompe disease
• Additional Relevant MeSH Terms: Metabolic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Genetic Diseases, Inborn; Carbohydrate Metabolism, Inborn Errors; Metabolism, Inborn Errors; Lysosomal Storage Diseases; Brain Diseases, Metabolic; Brain Diseases, Metabolic, Inborn; Lysosomal Storage Diseases, Nervous System; Glycogen Storage Disease; Glycogen Storage Disease Type II
• Other Study ID Numbers: 3190-RMB-CTIL

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No