Clinical trial NCT04755751: Exercise Capacity in Response to Enzyme Replacement Therapy in Pediatric Pompe Disease.
Official title: Acute and Long Term Evaluation of Exercise Capacity in Response to Enzyme Replacement Therapy in Pediatric Pompe Disease.
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Pompe Disease Infantile-Onset
Lead sponsor: Rambam Health Care Campus
Sponsor class: OTHER
First posted: 2021-02-16
Enrollment: 4
Sex: ALL
Minimum age (years): 5
Maximum age (years): 18
Standard ages: CHILD
ADULT
Observational model: CASE_ONLY
Time perspective: OTHER
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Children with Pompe disease who are followed at Ruth Children's Hospital will be evaluated. Diagnosis is confirmed in all cases by deficient GAA activity in cultured fibroblasts or by Ultra Performance Liquid Chromatography - Tandem Mass Spectrometer (UPLC-MS/MS) in DBS and mutational analysis of genomic DNA, isolated from peripheral blood leukocyte.

Brief summary: Our aims are to investigate the acute and long term effect of ERT on exercise capacity; comparing the effect of different ERT dosages (as prescribed by the clinician according to clinical judgment) and assessing the relationship between enzyme blood level and exercise capacity. Such evaluation may allow a more objective quantification of the response to ERT.

Detailed description: Pompe disease is a rare autosomal recessive metabolic myopathy caused by reduced or absence activity of the lysosomal enzyme acid alpha-glucosidase (GAA). Enzyme replacement therapy (ERT) with Myozyme has significantly improved the prospect of patients with infantile Pompe disease (IPD). Most IPD patients show clinical improvement on therapy, but deteriorate at different time points, raising the possibility that increasing drug delivery might halt the progression of the disease. Data on the effects of ERT therapy on physiological variables related to exercise tolerance is scarce.

Our aims are to investigate the acute and long term effect of ERT on exercise capacity; comparing the effect of different ERT dosages (as prescribed by the clinician according to clinical judgment) and assessing the relationship between enzyme blood level and exercise capacity. Such evaluation may allow a more objective quantification of the response to ERT.

Methods: A retrospective - prospective study evaluating pediatric patients with Pompe before and 2 days after ERT on multiple occasions and different dosing. Evaluation included cardiopulmonary exercise testing (CPET), 6 minute-walking test (6MWT), motor function test (GMFM-88) and self-collected blood samples (on a Guthrie card) for enzyme blood levels.

Eligibility criteria: Inclusion Criteria:

* Pompe patients \>5 years that have been on alpha-glucosidase (GAA).

Exclusion Criteria:

* Oxygen saturation \> 90% in room air without ventilatory assistance.
* Patients will be excluded if they required any invasive ventilation or if they required noninvasive ventilation while awake and upright

Primary outcomes:
measure: Exercise capacity
timeFrame: 1-6 years
Secondary outcomes:
measure: Six minute walk test
timeFrame: 1-6 years
measure: Motor function test
timeFrame: 1-6 years
measure: GAA enzyme level
timeFrame: 1-6 years
Other outcomes:
Locations:
city: Haifa
country: Israel
facility: Rambam Medical Center
Study officials:
affiliation: Rambam
name: Lea Bentur
role: PRINCIPAL_INVESTIGATOR
References: