Clinical trial NCT02838368: Investigating Pompe Prevalence in Neuromuscular Medicine Academic Practices
Official title: Investigating Pompe Prevalence in Neuromuscular Medicine Academic Practices
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Pompe Disease
Lead sponsor: University of California, Irvine
Sponsor class: OTHER
Collaborators: name: Genzyme, a Sanofi Company
First posted: 2016-07-20
Enrollment: 921
Sex: ALL
Minimum age (years): 8
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Patients age of 8 years and older suspected of late-onset Pompe disease.

Brief summary: The incidence of type II glycogen-storage disease (Pompe disease) varies depending on ethnicity and geographic region. As of 2010, nine studies have been published documenting the incidence of Pompe disease. It is most common within the African American population, with an incidence of 1 in 14,000. In the U.S. more broadly speaking, the combined incidence of all three variants of the disease is 1 in 40,000. These estimates relied on the frequencies of three mutations in the gene acid alpha-glucosidase (GAA), leading to variants of the disease. Criteria for inclusion in the studies were often non-selective; in many cases, molecular genetic screening was done at birth. With such a high prevalence of Pompe disease reported, it is expected that large university medical centers specializing in neuromuscular diseases would see a higher incidence of Pompe disease among their patients. From a comparable Italian multicenter study, it appears that Pompe disease accounts for 3% of all patients presenting with proximal weakness with or without CK elevation.

This study will measure the incidence of Pompe disease based on manifest laboratory abnormality, namely low GAA enzyme activity. Analysis of GAA enzyme activity will be determined through a blood sample of 4 mL. The study seeks to measure the epidemiology of Pompe disease by symptomatically screening all patients who present with symptoms of hitherto undiagnosed proximal weakness with or without elevation of the muscle enzyme, creatinine kinase (CK), or elevation of CK alone, at thirteen academic tertiary neuromuscular practices throughout the United States and Canada. Total recruitment is expected to be \~1,500 participants. It is anticipated that the number of incident Pompe cases in this cohort would be between 3-5%, i.e. 45-75 newly diagnosed cases of Pompe disease.


Eligibility criteria: Inclusion Criteria:

* Age 8 years or older.
* Geographically accessible to one of the sites.
* One of these following three clinical situations: Complaint of proximal muscle weakness with or without elevation in creatinine kinase (CK); neck muscle weakness (either flexor or extensor) with or without elevation in CK; or elevation of CK in isolation.
* Capable and willing to provide informed consent or assent and follow study procedures.

Exclusion Criteria:

* Less than 8 years of age.
* Subjects with an alternative neuromuscular diagnosis that is responsible for subject's symptoms
* Incapable or unwilling to provide informed consent and to follow research procedures.

Primary outcomes:
measure: The true incidence of Pompe disease among patients seen at neuromuscular clinics.
timeFrame: Two years
Secondary outcomes:
Other outcomes:
Locations:
city: Irvine
country: United States
facility: University of California, Irvine
state: California
Study officials:
affiliation: University of California, Irvine
name: Tahseen Mozaffar, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Cupler EJ, Berger KI, Leshner RT, Wolfe GI, Han JJ, Barohn RJ, Kissel JT; AANEM Consensus Committee on Late-onset Pompe Disease. Consensus treatment recommendations for late-onset Pompe disease. Muscle Nerve. 2012 Mar;45(3):319-33. doi: 10.1002/mus.22329. Epub 2011 Dec 15.
citation: Leslie N, Bailey L. Pompe Disease. 2007 Aug 31 [updated 2023 Nov 2]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews(R) [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2025. Available from http://www.ncbi.nlm.nih.gov/books/NBK1261/
citation: Hirschhorn R, Reuser AJ. Glycogen storage disease type II: acid alpha-glucosidase (acid maltase) deficiency. In: Scriver CR, Beaudet A, Sly WS, Valle D, eds. The Metabolic and Molecular Bases of Inherited Disease. New York, NY: McGraw-Hill; 2001:3389-420.
citation: Martiniuk F, Chen A, Mack A, Arvanitopoulos E, Chen Y, Rom WN, Codd WJ, Hanna B, Alcabes P, Raben N, Plotz P. Carrier frequency for glycogen storage disease type II in New York and estimates of affected individuals born with the disease. Am J Med Genet. 1998 Aug 27;79(1):69-72. doi: 10.1002/(sici)1096-8628(19980827)79:13.0.co;2-k. No abstract available.
citation: Musumeci O, la Marca G, Spada M, Mondello S, Danesino C, Comi GP, Pegoraro E, Antonini G, Marrosu G, Liguori R, Morandi L, Moggio M, Massa R, Ravaglia S, Di Muzio A, Filosto M, Tonin P, Di Iorio G, Servidei S, Siciliano G, Angelini C, Mongini T, Toscano A; Italian GSD II group. LOPED study: looking for an early diagnosis in a late-onset Pompe disease high-risk population. J Neurol Neurosurg Psychiatry. 2016 Jan;87(1):5-11. doi: 10.1136/jnnp-2014-310164. Epub 2015 Mar 17.
citation: Wencel M, Shaibani A, Goyal NA, Dimachkie MM, Trivedi J, Johnson NE, Gutmann L, Wicklund MP, Bandyopadhay S, Genge AL, Freimer ML, Goyal N, Pestronk A, Florence J, Karam C, Ralph JW, Rasheed Z, Hays M, Hopkins S, Mozaffar T. Investigating Late-Onset Pompe Prevalence in Neuromuscular Medicine Academic Practices: The IPaNeMA Study. Neurol Genet. 2021 Oct 18;7(6):e623. doi: 10.1212/NXG.0000000000000623. eCollection 2021 Dec.