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

NCT03694561 | Active Not Recruiting DMC

• 1 other identifier: Pro00100223
• Study Type: observational
• Target: 20
• Locations: 1 country
• Sites: 1

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. 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. 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. 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. 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

Conditions

Pompe Disease; Pompe Disease (Late-onset); GAA Deficiency

Keywords

Pompe disease; Glycogen Storage Disease Type II; Acid Maltase Deficiency; Acid Alpha-Glucosidase Deficiency; Alglucosidase alfa; Newborn Screening

Outcome Measures

Primary Outcomes (3)

• Medical records will be tracked for up to 4.5 years to document subtle musculoskeletal signs of Pompe disease.

  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.

  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.

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

  4.5 years

Secondary Outcomes (7)

• Medical records will be tracked for 4.5 years to document sleep quality.

  4.5 years

• Medical records will be tracked for 4.5 years to document auditory capacity.

  4.5 years

• Medical records will be tracked for 4.5 years to document cardiac involvement.

  4.5 years

• Medical records will be tracked for 4.5 years to document muscle architecture of the calves, para-spinal muscles and tongue

  4.5 years

• Medical records will be tracked for 4.5 years to document speech and swallow progression

  4.5 years

Study Arms (1)

Late-Onset Pompe disease

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

Other: Observational

Interventions

Observational OTHER

This study is a systematic investigation of the natural history of late-onset Pompe disease in infancy and childhood

Late-Onset Pompe disease

Eligibility Criteria

• Age: 3 Months - 54 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)
• Sampling Method: Non-Probability Sample

Study Population

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

You may qualify if:

• 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.

Sponsors & Collaborators

• Duke University: lead
• Genzyme, a Sanofi Company: collaborator

Study Sites (1)

Duke University

Durham, North Carolina, 27705, United States

Location

Related Publications (13)

• Chien YH, Hwu WL, Lee NC. Pompe disease: early diagnosis and early treatment make a difference. Pediatr Neonatol. 2013 Aug;54(4):219-27. doi: 10.1016/j.pedneo.2013.03.009. Epub 2013 Apr 28.

  PMID: 23632029 BACKGROUND

• Chien YH, Lee NC, Thurberg BL, Chiang SC, Zhang XK, Keutzer J, Huang AC, Wu MH, Huang PH, Tsai FJ, Chen YT, Hwu WL. Pompe disease in infants: improving the prognosis by newborn screening and early treatment. Pediatrics. 2009 Dec;124(6):e1116-25. doi: 10.1542/peds.2008-3667.

  PMID: 19948615 BACKGROUND

• Chien YH, Chiang SC, Zhang XK, Keutzer J, Lee NC, Huang AC, Chen CA, Wu MH, Huang PH, Tsai FJ, Chen YT, Hwu WL. Early detection of Pompe disease by newborn screening is feasible: results from the Taiwan screening program. Pediatrics. 2008 Jul;122(1):e39-45. doi: 10.1542/peds.2007-2222. Epub 2008 Jun 2.

  PMID: 18519449 BACKGROUND

• Chien YH, Lee NC, Chen CA, Tsai FJ, Tsai WH, Shieh JY, Huang HJ, Hsu WC, Tsai TH, Hwu WL. Long-term prognosis of patients with infantile-onset Pompe disease diagnosed by newborn screening and treated since birth. J Pediatr. 2015 Apr;166(4):985-91.e1-2. doi: 10.1016/j.jpeds.2014.10.068. Epub 2014 Nov 4.

  PMID: 25466677 BACKGROUND

• Feeney EJ, Austin S, Chien YH, Mandel H, Schoser B, Prater S, Hwu WL, Ralston E, Kishnani PS, Raben N. The value of muscle biopsies in Pompe disease: identifying lipofuscin inclusions in juvenile- and adult-onset patients. Acta Neuropathol Commun. 2014 Jan 2;2:2. doi: 10.1186/2051-5960-2-2.

  PMID: 24383498 BACKGROUND

• Hagemans ML, Hop WJ, Van Doorn PA, Reuser AJ, Van der Ploeg AT. Course of disability and respiratory function in untreated late-onset Pompe disease. Neurology. 2006 Feb 28;66(4):581-3. doi: 10.1212/01.wnl.0000198776.53007.2c.

  PMID: 16505317 BACKGROUND

• Hagemans ML, Winkel LP, Van Doorn PA, Hop WJ, Loonen MC, Reuser AJ, Van der Ploeg AT. Clinical manifestation and natural course of late-onset Pompe's disease in 54 Dutch patients. Brain. 2005 Mar;128(Pt 3):671-7. doi: 10.1093/brain/awh384. Epub 2005 Jan 19.

  PMID: 15659425 BACKGROUND

• Kishnani PS, Hwu WL, Mandel H, Nicolino M, Yong F, Corzo D; Infantile-Onset Pompe Disease Natural History Study Group. A retrospective, multinational, multicenter study on the natural history of infantile-onset Pompe disease. J Pediatr. 2006 May;148(5):671-676. doi: 10.1016/j.jpeds.2005.11.033.

  PMID: 16737883 BACKGROUND

• Kishnani PS, Steiner RD, Bali D, Berger K, Byrne BJ, Case LE, Crowley JF, Downs S, Howell RR, Kravitz RM, Mackey J, Marsden D, Martins AM, Millington DS, Nicolino M, O'Grady G, Patterson MC, Rapoport DM, Slonim A, Spencer CT, Tifft CJ, Watson MS. Pompe disease diagnosis and management guideline. Genet Med. 2006 May;8(5):267-88. doi: 10.1097/01.gim.0000218152.87434.f3. No abstract available.

  PMID: 16702877 BACKGROUND

• Kroos MA, Pomponio RJ, Hagemans ML, Keulemans JL, Phipps M, DeRiso M, Palmer RE, Ausems MG, Van der Beek NA, Van Diggelen OP, Halley DJ, Van der Ploeg AT, Reuser AJ. Broad spectrum of Pompe disease in patients with the same c.-32-13T->G haplotype. Neurology. 2007 Jan 9;68(2):110-5. doi: 10.1212/01.wnl.0000252798.25690.76.

  PMID: 17210890 BACKGROUND

• Laforet P, Laloui K, Granger B, Hamroun D, Taouagh N, Hogrel JY, Orlikowski D, Bouhour F, Lacour A, Salort-Campana E, Penisson-Besnier I, Sacconi S, Zagnoli F, Chapon F, Eymard B, Desnuelle C, Pouget J; French Pompe Registry Study Group. The French Pompe registry. Baseline characteristics of a cohort of 126 patients with adult Pompe disease. Rev Neurol (Paris). 2013 Aug-Sep;169(8-9):595-602. doi: 10.1016/j.neurol.2013.07.002. Epub 2013 Sep 3.

  PMID: 24008051 BACKGROUND

• Rairikar MV, Case LE, Bailey LA, Kazi ZB, Desai AK, Berrier KL, Coats J, Gandy R, Quinones R, Kishnani PS. Insight into the phenotype of infants with Pompe disease identified by newborn screening with the common c.-32-13T>G "late-onset" GAA variant. Mol Genet Metab. 2017 Nov;122(3):99-107. doi: 10.1016/j.ymgme.2017.09.008. Epub 2017 Sep 19.

  PMID: 28951071 BACKGROUND

• Wokke JH, Escolar DM, Pestronk A, Jaffe KM, Carter GT, van den Berg LH, Florence JM, Mayhew J, Skrinar A, Corzo D, Laforet P. Clinical features of late-onset Pompe disease: a prospective cohort study. Muscle Nerve. 2008 Oct;38(4):1236-45. doi: 10.1002/mus.21025.

  PMID: 18816591 BACKGROUND

MeSH Terms

Conditions

Glycogen Storage Disease Type II

Interventions

Watchful Waiting

Condition Hierarchy (Ancestors)

Lysosomal Storage Diseases, Nervous System; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Glycogen Storage Disease; Carbohydrate Metabolism, Inborn Errors; Lysosomal Storage Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Outcome Assessment, Health Care; Outcome and Process Assessment, Health Care; Quality of Health Care; Health Services Administration

Study Officials

• Priya Kishnani, MD

  Duke University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 1, 2018
• First Posted: October 3, 2018
• Study Start: March 25, 2019
• Primary Completion (Estimated): August 31, 2027
• Study Completion (Estimated): August 31, 2027
• Last Updated: September 22, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)