Exercise Capacity in Response to Enzyme Replacement Therapy in Pediatric Pompe Disease.

Acute and Long Term Evaluation of Exercise Capacity in Response to Enzyme Replacement Therapy in Pediatric Pompe Disease.

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.

Study Overview

• Status: Recruiting
• Conditions: Pompe Disease Infantile-Onset
• Intervention / Treatment: Diagnostic test: Cardiopulmonary exercise testing (CPET)

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.

• Study Type: Observational
• Enrollment (Anticipated): 4

Contacts and Locations

• Study Contact: Name: Lea Bentur; Phone Number: +972-4-7774360; Email: l_bentur@rambam.health.gov.il

Study Locations

• Israel
  • Haifa, Israel
    • Recruiting
    • Rambam Medical Center
    • Contact: Ronen Bar-Yoseph, MD; Phone Number: +972-4-7774360; Email: r_bar-yoseph@rmc.gov.il

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 5 years to 18 years (Child, Adult)
• Accepts Healthy Volunteers: N/A
• Genders Eligible for Study: All

• 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.

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Pediatric Pompe patients; 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.

Diagnostic test: Cardiopulmonary exercise testing (CPET); CPET using a cycle ergometer (COSMED, Rome, Italy) beginning with a no resistance warm up lasting 1 to 3 minutes and followed with an incrementing resistance adapted to the patient's functional capacities according to the examiner's free judgment and ranging from no resistance (20 Rounds Per Minute (RPM)/minute) 5 to 20 Watts/minute on ramps or by successive stages

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Exercise capacity	Oxygen uptake evaluated by cardiopulmonary exercise testing (CPET)	1-6 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Six minute walk test	The distance gained after six minute of habitual walking.	1-6 years
Motor function test	Motor function test (GMFM-88) as assessed by experience physiotherapy.	1-6 years
GAA enzyme level	Self-collected blood samples (on a Guthrie card) for lysosomal enzyme acid alpha-glucosidase (GAA) blood levels.	1-6 years

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): June 24, 2018
• Primary Completion (Anticipated): January 1, 2023
• Study Completion (Anticipated): January 1, 2024

Study Registration Dates

• First Submitted: February 10, 2021
• First Submitted That Met QC Criteria: February 14, 2021
• First Posted (Actual): February 16, 2021

Study Record Updates

• Last Update Posted (Actual): February 16, 2021
• Last Update Submitted That Met QC Criteria: February 14, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• 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: RMB-045-18

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: IPD is not planned to be available.

Drug and device information, study documents

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