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

Sponsor:

Collaborators:

Information provided by (Responsible Party):

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Tracking Information

First Submitted Date ^ICMJE

October 1, 2018

First Posted Date ^ICMJE

October 3, 2018

Last Update Posted Date

October 3, 2018

Actual Study Start Date ^ICMJE

October 2018

Estimated Primary Completion Date

October 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures ^ICMJE

Medical records will be tracked for 5 years to document subtle musculoskeletal signs of Pompe disease.[ Time Frame: 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 5 years to document Pompe-specific clinical symptoms.[ Time Frame: 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.

Medical records will be tracked for 5 years to document elevation in Pompe-specific biomarkers from blood and urine samples.[ Time Frame: 5 years ]

This outcome measure will be tested by comparing lab results to lab-specific ranges.

Original Primary Outcome Measures ^ICMJE

Same as current

Current Secondary Outcome Measures ^ICMJE

Medical records will be tracked for 5 years to document sleep quality.[ Time Frame: 5 years ]
This outcome measure will be tested qualitatively by questionnaire.
Medical records will be tracked for 5 years to document auditory capacity.[ Time Frame: 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 5 years to document cardiac involvement.[ Time Frame: 5 years ]
This outcome measure will be analyzed by echocardiogram and electrocardiogram results.
Medical records will be tracked for 5 years to document muscle architecture of the calves, para-spinal muscles and tongue[ Time Frame: 5 years ]
This outcome measure will be tested qualitatively by simple ultrasound examination.
Medical records will be tracked for 5 years to document speech and swallow progression[ Time Frame: 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.

Descriptive Information

Brief Title ^ICMJE

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

Official Title ^ICMJE

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

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 and infants with Pompe disease without cardiomyopathy identified in newborn screening(NBS). The study has three goals: 1. To study and record disease specific clinical symptoms in newborns and infants with Pompe disease without cardiomyopathy (disease of the heart muscle) 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 3. To determine criteria to start preventative therapies including enzyme replacement therapy (ERT) in patients with clinical features of Pompe disease identified 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 40 infants at Duke that has screened for LOPD. This study involves minimal risk to the patient and offers a potential benefit of improved disease management. The initial visit will be as soon as possible after a confirmed LOPD diagnosis and at 6-9 month intervals. The investigators will continue to gather clinical information on patients and monitor clinical status beyond assessment at three time points. The study has three goals: 1. To study and record disease specific clinical symptoms in newborns and infants with Pompe disease without cardiomyopathy (disease of the heart muscle) 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 3. To determine criteria to start preventative therapies including enzyme replacement therapy (ERT) in patients with clinical features of Pompe disease identified via NBS

Study Type ^ICMJE

Observational

Study Phase

Study Design ^ICMJE

Allocation:
Intervention Model:
Intervention Model Description:
Masking: Observational
Masking Description:
Primary Purpose:

Condition ^ICMJE

Intervention ^ICMJE

Other: Observational
This study is a systematic investigation of the natural history of late-onset Pompe disease in infancy

Study Arms

: Late-Onset Pompe disease
Individuals with a confirmed diagnosis of Late-Onset Pompe disease via NBS

Recruitment Information

Recruitment Status ^ICMJE

Not yet recruiting

Estimated Enrollment ^ICMJE

Original Estimated Enrollment ^ICMJE

Same as current

Estimated Study Completion Date

October 2023

Estimated Primary Completion Date

October 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria ^ICMJE

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

Sex/Gender

Sexes Eligible for Study:

All

Ages

N/A and older (Adult, Older Adult)

Accepts Healthy Volunteers

Listed Location Countries ^ICMJE

Removed Location Countries

Administrative Information

Has Data Monitoring Committee

U.S. FDA-regulated Product

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

Plan to Share IPD:

Responsible Party

，

Study Sponsor ^ICMJE

Duke University

Collaborators ^ICMJE

Investigators ^ICMJE

Principal Investigator: Priya Kishnani, MD Duke University

PRS Account

Verification Date

October 2018

^ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

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