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

October 25, 2023 updated by: Duke University

Developing a Management Approach for Patients With "Late-Onset" Pompe Disease GAA Variant Identified by Newborn Screening

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

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

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 Type

Observational

Enrollment (Estimated)

20

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • North Carolina
      • Durham, North Carolina, United States, 27705
        • Duke University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

3 months to 4 years (Child)

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

Participants who have been diagnosed with Late-Onset Pompe Disease via Newborn Screening (NBS)

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Late-Onset Pompe disease
Individuals with a confirmed diagnosis of Late-Onset Pompe disease via NBS
Other: Observational
This study is a systematic investigation of the natural history of late-onset Pompe disease in infancy and childhood

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Medical records will be tracked for up to 4.5 years to document subtle musculoskeletal signs of Pompe disease.
Time Frame: 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.
4.5 years
Medical records will be tracked for up to 4.5 years years to document Pompe-specific clinical symptoms.
Time Frame: 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.
4.5 years
Medical records will be tracked for 4.5 years to document elevation in Pompe-specific biomarkers from blood and urine samples.
Time Frame: 4.5 years
This outcome measure will be tested by comparing lab results to lab-specific ranges.
4.5 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Medical records will be tracked for 4.5 years to document sleep quality.
Time Frame: 4.5 years
This outcome measure will be tested qualitatively by questionnaire.
4.5 years
Medical records will be tracked for 4.5 years to document auditory capacity.
Time Frame: 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.
4.5 years
Medical records will be tracked for 4.5 years to document cardiac involvement.
Time Frame: 4.5 years
This outcome measure will be analyzed by echocardiogram and electrocardiogram results.
4.5 years
Medical records will be tracked for 4.5 years to document muscle architecture of the calves, para-spinal muscles and tongue
Time Frame: 4.5 years
This outcome measure will be tested qualitatively by simple ultrasound examination.
4.5 years
Medical records will be tracked for 4.5 years to document speech and swallow progression
Time Frame: 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.
4.5 years
Change in parental coping overtime using quality of life questionnaires after a child is diagnosed with late onset Pompe disease via NBS.
Time Frame: 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'.
yearly, up to 4.5 years
Change in parent's emotional distress overtime using PROMIS questionnaire
Time Frame: 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.
yearly, up to 4.5 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Duke University

Collaborators

Genzyme, a Sanofi Company

Investigators

  • Principal Investigator: Priya Kishnani, MD, Duke University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 25, 2019

Primary Completion (Estimated)

August 31, 2024

Study Completion (Estimated)

August 31, 2024

Study Registration Dates

First Submitted

October 1, 2018

First Submitted That Met QC Criteria

October 1, 2018

First Posted (Actual)

October 3, 2018

Study Record Updates

Last Update Posted (Actual)

October 26, 2023

Last Update Submitted That Met QC Criteria

October 25, 2023

Last Verified

September 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Pro00100223

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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