Determination of CRIM Status and Longitudinal Follow-up of Individuals With Pompe Disease

NCT01665326 | Recruiting DMC

• 1 other identifier: Pro00001562
• Study Type: observational
• Target: 400
• Locations: 1 country
• Sites: 1

Brief Summary

This is a longitudinal natural history study of Infantile Pompe disease. The investigators will regularly collect and review medical information regarding the diagnosis of Pompe disease, response to enzyme replacement (ERT) using alglucosidase alfa (Lumizyme/Myozyme) and response to immunosuppressive therapy in cases at risk for developing or those who have developed high and sustained antibodies to ERT. To follow the long-term outcomes, we will collect medical records including but not limited to the diagnosis, clinical parameters, assessments for clinical monitoring, and laboratory values including antibody testing results.

Conditions

Pompe Disease

Keywords

Pompe disease; Glycogen Storage Disease Type II; Acid Maltase Deficiency; CRIM Status; Acid Alpha-Glucosidase Deficiency; Alglucosidase alfa; Myozyme; Enzyme replacement therapy; Immune Tolerance Induction; Lumizyme; Immunomodulation; Anti-drug antibodies

Outcome Measures

Primary Outcomes (1)

• Clinical response to enzyme replacement therapy (ERT) using alglucosidase alfa (Myozyme)

  Medical records will be tracked until the patient reaches the age of 18 years to follow clinical response to ERT. This will allow us to gain an understanding of CRIM status in relation to clinical outcomes and development for these subjects.

  Up to 18 years

Secondary Outcomes (1)

• Response to Immune Tolerance Induction (ITI)

  Up to 18 years

Study Arms (1)

Infantile Pompe disease

Individuals with a confirmed diagnosis of Infantile Pompe disease

Other: Observational

Interventions

Observational OTHER

This is a longitudinal study focused on the emerging natural history of Infantile Pompe disease, response to ERT using alglucosidase alfa (Myozyme) and response to Immune Tolerance Induction (ITI).

Infantile Pompe disease

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Study subjects will be babies/children/adults with a confirmed diagnosis of infantile-onset Pompe disease who are: 1. seen by the clinical staff of Duke Division of Medical Genetics, or 2. whose physician or parent contacts the Duke Division of Medical Genetics with the wish to participate in this CRIM research study.

You may qualify if:

• Confirmed diagnosis of infantile, atypical or juvenile onset Pompe disease
• Must provide a written informed consent

Sponsors & Collaborators

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

Study Sites (1)

Duke University Medical Center

Durham, North Carolina, 27710, United States

RECRUITING

Related Publications (17)

• Banugaria SG, Prater SN, Ng YK, Kobori JA, Finkel RS, Ladda RL, Chen YT, Rosenberg AS, Kishnani PS. The impact of antibodies on clinical outcomes in diseases treated with therapeutic protein: lessons learned from infantile Pompe disease. Genet Med. 2011 Aug;13(8):729-36. doi: 10.1097/GIM.0b013e3182174703.

  PMID: 21637107 RESULT

• Messinger YH, Mendelsohn NJ, Rhead W, Dimmock D, Hershkovitz E, Champion M, Jones SA, Olson R, White A, Wells C, Bali D, Case LE, Young SP, Rosenberg AS, Kishnani PS. Successful immune tolerance induction to enzyme replacement therapy in CRIM-negative infantile Pompe disease. Genet Med. 2012 Jan;14(1):135-42. doi: 10.1038/gim.2011.4.

  PMID: 22237443 RESULT

• Mendelsohn NJ, Messinger YH, Rosenberg AS, Kishnani PS. Elimination of antibodies to recombinant enzyme in Pompe's disease. N Engl J Med. 2009 Jan 8;360(2):194-5. doi: 10.1056/NEJMc0806809. No abstract available.

  PMID: 19129538 RESULT

• Berrier KL, Kazi ZB, Prater SN, Bali DS, Goldstein J, Stefanescu MC, Rehder CW, Botha EG, Ellaway C, Bhattacharya K, Tylki-Szymanska A, Karabul N, Rosenberg AS, Kishnani PS. CRIM-negative infantile Pompe disease: characterization of immune responses in patients treated with ERT monotherapy. Genet Med. 2015 Nov;17(11):912-8. doi: 10.1038/gim.2015.6. Epub 2015 Mar 5.

  PMID: 25741864 RESULT

• Banugaria SG, Prater SN, Patel TT, Dearmey SM, Milleson C, Sheets KB, Bali DS, Rehder CW, Raiman JA, Wang RA, Labarthe F, Charrow J, Harmatz P, Chakraborty P, Rosenberg AS, Kishnani PS. Algorithm for the early diagnosis and treatment of patients with cross reactive immunologic material-negative classic infantile pompe disease: a step towards improving the efficacy of ERT. PLoS One. 2013 Jun 25;8(6):e67052. doi: 10.1371/journal.pone.0067052. Print 2013.

  PMID: 23825616 RESULT

• Kazi ZB, Desai AK, Troxler RB, Kronn D, Packman S, Sabbadini M, Rizzo WB, Scherer K, Abdul-Rahman O, Tanpaiboon P, Nampoothiri S, Gupta N, Feigenbaum A, Niyazov DM, Sherry L, Segel R, McVie-Wylie A, Sung C, Joseph AM, Richards S, Kishnani PS. An immune tolerance approach using transient low-dose methotrexate in the ERT-naive setting of patients treated with a therapeutic protein: experience in infantile-onset Pompe disease. Genet Med. 2019 Apr;21(4):887-895. doi: 10.1038/s41436-018-0270-7. Epub 2018 Sep 14.

  PMID: 30214072 RESULT

• Desai AK, Walters CK, Cope HL, Kazi ZB, DeArmey SM, Kishnani PS. Enzyme replacement therapy with alglucosidase alfa in Pompe disease: Clinical experience with rate escalation. Mol Genet Metab. 2018 Feb;123(2):92-96. doi: 10.1016/j.ymgme.2017.12.435. Epub 2017 Dec 23.

  PMID: 29289479 RESULT

• McIntosh PT, Hobson-Webb LD, Kazi ZB, Prater SN, Banugaria SG, Austin S, Wang R, Enterline DS, Frush DP, Kishnani PS. Neuroimaging findings in infantile Pompe patients treated with enzyme replacement therapy. Mol Genet Metab. 2018 Feb;123(2):85-91. doi: 10.1016/j.ymgme.2017.10.005. Epub 2017 Oct 13.

  PMID: 29050825 RESULT

• Rairikar M, Kazi ZB, Desai A, Walters C, Rosenberg A, Kishnani PS. High dose IVIG successfully reduces high rhGAA IgG antibody titers in a CRIM-negative infantile Pompe disease patient. Mol Genet Metab. 2017 Sep;122(1-2):76-79. doi: 10.1016/j.ymgme.2017.05.006. Epub 2017 May 18.

  PMID: 28648664 RESULT

• Kazi ZB, Desai AK, Berrier KL, Troxler RB, Wang RY, Abdul-Rahman OA, Tanpaiboon P, Mendelsohn NJ, Herskovitz E, Kronn D, Inbar-Feigenberg M, Ward-Melver C, Polan M, Gupta P, Rosenberg AS, Kishnani PS. Sustained immune tolerance induction in enzyme replacement therapy-treated CRIM-negative patients with infantile Pompe disease. JCI Insight. 2017 Aug 17;2(16):e94328. doi: 10.1172/jci.insight.94328. eCollection 2017 Aug 17.

  PMID: 28814660 RESULT

• Spiridigliozzi GA, Keeling LA, Stefanescu M, Li C, Austin S, Kishnani PS. Cognitive and academic outcomes in long-term survivors of infantile-onset Pompe disease: A longitudinal follow-up. Mol Genet Metab. 2017 Jun;121(2):127-137. doi: 10.1016/j.ymgme.2017.04.014. Epub 2017 May 1.

  PMID: 28495044 RESULT

• Kazi ZB, Prater SN, Kobori JA, Viskochil D, Bailey C, Gera R, Stockton DW, McIntosh P, Rosenberg AS, Kishnani PS. Durable and sustained immune tolerance to ERT in Pompe disease with entrenched immune responses. JCI Insight. 2016 Jul 21;1(11):e86821. doi: 10.1172/jci.insight.86821.

  PMID: 27493997 RESULT

• Bali DS, Goldstein JL, Rehder C, Kazi ZB, Berrier KL, Dai J, Kishnani PS. Clinical Laboratory Experience of Blood CRIM Testing in Infantile Pompe Disease. Mol Genet Metab Rep. 2015 Dec 1;5:76-79. doi: 10.1016/j.ymgmr.2015.10.012.

  PMID: 26693141 RESULT

• Curelaru S, Desai AK, Fink D, Zehavi Y, Kishnani PS, Spiegel R. A favorable outcome in an infantile-onset Pompe patient with cross reactive immunological material (CRIM) negative disease with high dose enzyme replacement therapy and adjusted immunomodulation. Mol Genet Metab Rep. 2022 Jul 6;32:100893. doi: 10.1016/j.ymgmr.2022.100893. eCollection 2022 Sep.

  PMID: 35813979 RESULT

• Li C, Desai AK, Gupta P, Dempsey K, Bhambhani V, Hopkin RJ, Ficicioglu C, Tanpaiboon P, Craigen WJ, Rosenberg AS, Kishnani PS. Transforming the clinical outcome in CRIM-negative infantile Pompe disease identified via newborn screening: the benefits of early treatment with enzyme replacement therapy and immune tolerance induction. Genet Med. 2021 May;23(5):845-855. doi: 10.1038/s41436-020-01080-y. Epub 2021 Jan 25.

  PMID: 33495531 RESULT

• Desai AK, Baloh CH, Sleasman JW, Rosenberg AS, Kishnani PS. Benefits of Prophylactic Short-Course Immune Tolerance Induction in Patients With Infantile Pompe Disease: Demonstration of Long-Term Safety and Efficacy in an Expanded Cohort. Front Immunol. 2020 Aug 6;11:1727. doi: 10.3389/fimmu.2020.01727. eCollection 2020.

  PMID: 32849613 RESULT

• Buckley AF, Desai AK, Ha CI, Petersen MA, Estrada JC, Water fi eld JR, Bossen EH, Kishnani PS. Outside the fiber: Endomysial stromal and capillary pathology in skeletal muscle may impede infusion therapy in infantile-onset Pompe disease. J Neuropathol Exp Neurol. 2023 Mar 20;82(4):345-362. doi: 10.1093/jnen/nlad012.

  PMID: 36864705 DERIVED

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 S Kishnani, MD

  Duke University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ankit K Desai, MBBS

CONTACT

919-613-6310; ankit.desai@duke.edu

Eleanor Rodriguez-Rassi, MPH

CONTACT

919-613-1219; eleanor.rodriguezrassi@duke.edu

Study Design

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

Study Record Dates

• First Submitted: August 13, 2012
• First Posted: August 15, 2012
• Study Start: September 1, 2009
• Primary Completion (Estimated): March 1, 2028
• Study Completion (Estimated): March 1, 2029
• Last Updated: April 8, 2026

Record last verified: 2026-04

Locations

US (1)