Developing a Management Approach for Patients With "Late-Onset" Pompe Disease

Active, not recruiting

• Conditions: Pompe Disease; Pompe Disease (Late-onset); GAA Deficiency
• Interventions: Other: Observational

• Registration Number: NCT03694561
• Lead Sponsor: Duke University

Brief Summary

This is an observational study with no study related treatment of interventions. The purpose of the study is to investigate and document disease specific clinical symptoms in newborns, infants and children with Pompe disease without cardiomyopathy identified in newborn screening(NBS).

There will be baseline, months 6 and months 12 visits for infants and newborns (infants study). For children of ages 24 months to 54 months, there will be baseline, year 1 and year 2 visits (children study).

The study has four goals:

1. To study and record disease specific clinical symptoms in newborns, infants and children with Pompe disease without cardiomyopathy (disease of the heart muscle) in the first year of life identified through newborn screening (NBS)

2. To devise an approach to characterize early musculoskeletal (muscles and joints) involvement in subjects with the "late-onset" GAA variant identified by NBS including ability to collect research information via virtual health platforms.

3. To determine criteria to start preventative therapies including enzyme replacement therapy (ERT) in patients with clinical features of Pompe disease identified via NBS

4. To document parental coping and anxiety/emotional distress overtime using quality of life questionnaires after a child is diagnosed with late onset Pompe disease via NBS

Detailed Description

Late-Onset Pompe Disease(LOPD) is an inherited disorder caused by lack of or defect in the enzyme acid alpha-glucosidase (GAA). GAA enzyme deficiency causes glycogen to build up and damage cells throughout the body, especially in the heart and muscles. In LOPD, subtle and overt disease-specific features may go unrecognized in childhood without vigilant clinical examination and assessments with appropriate functional tests. In our clinical experience, children with the "late-onset" GAA variant may present much earlier in life and adult patients with LOPD consistently report a much earlier symptom onset and a significant diagnostic delay. These patients have shown improvement after initiation of ERT but have motor impairments adversely affecting their quality of life and growth from early childhood. Therefore, earlier diagnosis and initiation of ERT is crucial in these patients. Instituting ERT at an ideal time may prevent/reduce these irreversible musculoskeletal impairments and lead to a better quality of life and less disease burden as these children age.

Our team of Pompe disease experts will perform detailed clinical evaluations, physical therapy evaluations, cardiac assessments, speech and swallow evaluations, biochemical tests, sleep questionnaire, and hearing assessments on these patients. These assessments will allow use to capture and describe the earlier clinical phenotype in these patients and provide insights into the early signs and symptoms of LOPD.This study will provide and evidence-based approach to clinical management of newborns with LOPD to primary care physicians and geneticists, leading to improves patient outcomes.

The investigators will enroll 20 infants and children at Duke that has screened for LOPD. This study involves minimal risk to the patient and offers a potential benefit of improved disease management. For infants, the initial visit will be as soon as possible after a confirmed LOPD diagnosis and follow up visits will be at 6 months and 12 months. The investigators will continue to gather clinical information on patients and monitor clinical status beyond assessment at three time points. For children of ages 24 months to 54 months, there will be baseline, year 1 and year 2 visits.

The study has four goals:

1. To study and record disease specific clinical symptoms in newborns, infants and children with Pompe disease without cardiomyopathy (disease of the heart muscle) in the first year of life identified through newborn screening (NBS)

2. To devise an approach to characterize early musculoskeletal (muscles and joints) involvement in subjects with the "late-onset" GAA variant identified by NBS including ability to collect research information via virtual health platforms.

3. To determine criteria to start preventative therapies including enzyme replacement therapy (ERT) in patients with clinical features of Pompe disease identified via NBS

4. To document parental coping and anxiety/emotional distress overtime using quality of life questionnaires after a child is diagnosed with late onset Pompe disease via NBS

Study Timeline

• Study First Submitted: 2018-10-01
• Study First Submitted QC: 2018-10-01
• Study First Posted: 2018-10-03
• Study Start: 2019-03-25
• Status Verified: 2023-09
• Last Update Submitted: 2023-10-25
• Last Update Posted: 2023-10-26
• Primary Completion: 2024-08-31
• Study Completion: 2024-08-31

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 20

Inclusion Criteria

• Subject has been diagnosed via newborn screening
• Subject has a confirmed and documented diagnosis of Pompe disease and absence of cardiac involvement
• Subject has predicted "late-onset" GAA variants such as c.-32-13T>G, c.2188G>T, c.1935C>A, c.1726G>A, c.118C>T etc. in homozygosity or compound heterozygosity
• Subject must be between 3 and 20 months for infant study or between 24 and 54 months (+/- 3 months) for children study at time of enrollment.

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Late-Onset Pompe disease	Observational	Individuals with a confirmed diagnosis of Late-Onset Pompe disease via NBS

Primary Outcome Measures

Name	Time	Method
Medical records will be tracked for up to 4.5 years to document subtle musculoskeletal signs of Pompe disease.	4.5 years	This outcome measure will be tested individually by a formal physical therapy assessment, Alberta Infant Motor Scale (AIMS), Gross Motor Functional Measure (GMFM), Hammersmith Functional Motor Scale Expanded(HFMSE),Modified Hammersmith Functional Motor Scale Extend(MHMFS-EXTEND), and Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders(CHOP INTEND) to give a combined assessment score.
Medical records will be tracked for 4.5 years to document elevation in Pompe-specific biomarkers from blood and urine samples.	4.5 years	This outcome measure will be tested by comparing lab results to lab-specific ranges.
Medical records will be tracked for up to 4.5 years years to document Pompe-specific clinical symptoms.	4.5 years	This outcome measure will be tested individually by physical examination, nutritional evaluation and functional assessment to give a combined analysis of Pompe-specific symptoms.

Secondary Outcome Measures

Name	Time	Method
Medical records will be tracked for 4.5 years to document sleep quality.	4.5 years	This outcome measure will be tested qualitatively by questionnaire.
Change in parental coping overtime using quality of life questionnaires after a child is diagnosed with late onset Pompe disease via NBS.	yearly, up to 4.5 years	BRIEF COPE is completed by the patient's parent or guardian. BRIEF COPE is rated on a scale of 1-4 with 1 = 'I haven't been doing this at all' and 4 = 'I've been doing this a lot'.
Change in parent's emotional distress overtime using PROMIS questionnaire	yearly, up to 4.5 years	The PROMIS questionnaire is completed by the patient's parent or guardian. Emotional distress is rated on a scale of 1-5 with 1=never and 5=always.
Medical records will be tracked for 4.5 years to document auditory capacity.	4.5 years	This outcome measure will be tested individually by visual reinforcement audiology (VRA) and distortion product optoacoustic emissions (DPOAE) to give a combined assessment score.
Medical records will be tracked for 4.5 years to document speech and swallow progression	4.5 years	This outcome measure will be tested individually by using videofluoroscopic study, Preschool Language Scale-Fourth Edition(PLS4), Receptive-Expressive Emergent Language Test Third Edition(REEL3), Pediatric Eating Assessment Tool (PEDI EAT-10), Functional Oral Intake Scale(FOIS) and serial photographs to give a combined assessment score.
Medical records will be tracked for 4.5 years to document cardiac involvement.	4.5 years	This outcome measure will be analyzed by echocardiogram and electrocardiogram results.
Medical records will be tracked for 4.5 years to document muscle architecture of the calves, para-spinal muscles and tongue	4.5 years	This outcome measure will be tested qualitatively by simple ultrasound examination.

Trial Locations

Locations (1)

Duke University; 🇺🇸 Durham, North Carolina, United States