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

Study Status: Completed
Recruit Status: Completed
Study Type: Observational

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

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 Summary:

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
Sponsor: Rambam Health Care Campus

Current Primary Outcome: Change in oxygen Uptake [ Time Frame: 3 days ]

Change in mount of oxygen consumed per amount of time measured during 15 minutes of an exercise test.


Original Primary Outcome: Change in oxygen Uptake [ Time Frame: 3 days (between visit 1 and 2) ]

Change in mount of oxygen consumed per amount of time measured during 15 minutes of an exercise test.


Current Secondary Outcome:

  • 6 Minute walk test [ Time Frame: 3 days ]
    The distance an individual walked in 6 minutes.
  • Gross motor function measure score sheet (GMFM-88) [ Time Frame: 3 days ]
    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.
  • Spirometry [ Time Frame: 3 days. ]
    Pulmonary function as assessed by spirometry. Evaluation time - 5 minutes.


Original Secondary Outcome:

  • 6 Minute walk test [ Time Frame: Six minutes of walking at visit 1 and 2 ]
    The distance an individual walked in 6 minutes.
  • Gross motor function measure score sheet (GMFM-88) [ Time Frame: Thirty minutes of evaluation at visit 1 and 2 ]
    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.
  • Spirometry [ Time Frame: 5 minutes of evaluation, completed pre and post exercise test at visit 1 and 2. ]
    Pulmonary function as assessed by spirometry.


Information By: Rambam Health Care Campus

Dates:
Date Received: April 30, 2017
Date Started: January 1, 2014
Date Completion:
Last Updated: May 14, 2017
Last Verified: May 2017