Clinical trial NCT03147664: Cardiopulmonary Exercise Test to Quantify Enzyme Replacement Response in Pediatric Pompe Disease
Official title: Cardiopulmonary Exercise Test to Quantify Enzyme Replacement Response in Pediatric Pompe Disease
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Enzyme Replacement Therapy in Pompe Disease
Keywords: pompe disease
exercise capacity
cardiopulmonary exercise testing
Lead sponsor: Rambam Health Care Campus
Sponsor class: OTHER
First posted: 2017-05-10
Enrollment: 5
Sex: ALL
Minimum age (years): 8
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
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.

Brief summary: 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).

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Change in oxygen Uptake
timeFrame: 3 days
Secondary outcomes:
measure: 6 Minute walk test
timeFrame: 3 days
measure: Gross motor function measure score sheet (GMFM-88)
timeFrame: 3 days
measure: Spirometry
timeFrame: 3 days.
Other outcomes:
Locations:
Study officials:
affiliation: Rambam Health Care Campus
name: Lea Bentur, Prof.
role: PRINCIPAL_INVESTIGATOR
References: