Determination of CRIM Status and Longitudinal Follow-up of Individuals With Pompe Disease
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ClinicalTrials.gov Identifier: NCT01665326 |
Recruitment Status
:
Recruiting
First Posted
: August 15, 2012
Last Update Posted
: July 14, 2017
|
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This is a longitudinal natural history study of Infantile Pompe disease. The investigators will regularly collect and review medical information for up to 10 years regarding the diagnosis of Pompe disease, response to enzyme replacement (ERT) using alglucosidase alfa (Myozyme) and response to immunosuppressive therapy in cases at risk for developing or those who have developed high and sustained antibodies to ERT. A subset of de-identified information about the natural history of Pompe disease and the response to treatment will be incorporated into the Lysosomal Disease Network (LDN) disease registry. The LDN is a nonprofit organization of scientists located around the world whose research focuses on Lysosomal disease.
The specific aims of this study are:
- To determine and correlate Cross-Reactive Immunological Material (CRIM) status with the GAA gene mutations found on these patients
- To validate an approach for determining CRIM status from whole blood sample, with the gold standard determination of CRIM status by skin fibroblasts and mutation analysis
- To explore the clinical treatment response and natural history of CRIM-positive and CRIM-negative Pompe disease patients with and without immune modulation
- To investigate the role of immune response to treatment
Condition or disease | Intervention/treatment |
---|---|
Pompe Disease | Other: Observational |
Infantile-onset Pompe disease 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, which is normally diagnosed within the first months of life. Current treatment for Pompe disease involves enzyme replacement therapy (ERT) using the drug alglucosidase alfa (Myozyme), which provides a form of the GAA enzyme to replace the enzyme that is missing or not working properly in the patient's blood.
In this study, the investigators will learn about the patient's ability to tolerate ERT. Cross-Reactive Immunological Material (CRIM) is a measurement of natural GAA production and an important factor that affects how patients respond to ERT with Myozyme. Children who produce some natural GAA are classified as CRIM positive (+), while children who do not produce any natural GAA are classified as CRIM negative (-). Children who are CRIM+ generally tolerate ERT well. But, children who are CRIM-, and some children classified as CRIM+, have a poor response to ERT due to complications from an immune response against the drug. Treatments are currently being developed to stop this immune response and prevent complications from ERT.
This is a longitudinal natural history study of Infantile Pompe disease. The investigators will regularly collect and review medical information for up to 10 years regarding the diagnosis of Pompe disease, response to enzyme replacement (ERT) using alglucosidase alfa (Myozyme) and response to immunosuppressive therapy in cases at risk for developing or those who have developed high and sustained antibodies to ERT. A subset of de-identified information about the natural history of Pompe disease and the response to treatment will be incorporated into the Lysosomal Disease Network (LDN) disease registry. The LDN is a nonprofit organization of scientists located around the world whose research focuses on Lysosomal disease.
The specific aims of this study are:
- To determine and correlate Cross-Reactive Immunological Material (CRIM) status with the GAA gene mutations found on these patients
- To validate an approach for determining CRIM status from whole blood sample, with the gold standard determination of CRIM status by skin fibroblasts and mutation analysis
- To explore the clinical treatment response and natural history of CRIM-positive and CRIM-negative Pompe disease patients with and without immune modulation
- To investigate the role of immune response to treatment
Study Type : | Observational |
Estimated Enrollment : | 300 participants |
Observational Model: | Cohort |
Time Perspective: | Prospective |
Official Title: | Determination of Cross-Reactive Immunological Material (CRIM) Status and Longitudinal Follow-up of Individuals With Pompe Disease |
Study Start Date : | September 2009 |
Estimated Primary Completion Date : | August 2019 |
Estimated Study Completion Date : | August 2019 |
Group/Cohort | Intervention/treatment |
---|---|
Infantile Pompe disease
Individuals with a confirmed diagnosis of Infantile Pompe disease
|
Other: Observational
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).
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- Clinical response to enzyme replacement therapy (ERT) using alglucosidase alfa (Myozyme) [ Time Frame: Up to 10 years ]Medical records will be tracked for up to 10 years to follow clinical response to ERT. This will allow us to gain an understanding of CRIM status in relation to clinical outcome and development for these subjects.
- Response to Immune Tolerance Induction (ITI) [ Time Frame: Up to 10 years ]Medical records will be tracked for up to 10 years to follow clinical response to Immune Tolerance Induction (ITI) for patients who are CRIM- or CRIM+ with high antibody titers. This will allow us to increase our understanding of the history of Pompe disease in relation to treatment interventions and the role of high antibody titers in terms of patient outcome in order to develop strategies to ameliorate the immune response and other factors that may affect response to ERT.

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Ages Eligible for Study: | up to 18 Years (Child, Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Sampling Method: | Non-Probability Sample |
Study subjects will be babies/children with a confirmed diagnosis of infantile-onset Pompe disease who are:
- seen by the clinical staff of Duke Division of Medical Genetics, or
- whose physician or parent contacts the Duke Division of Medical Genetics with the wish to participate in this CRIM research study.
Inclusion Criteria:
- Confirmed diagnosis of infantile, atypical or juvenile onset Pompe disease
- Must have a parent or guardian provide written informed consent
Exclusion Criteria:
- Age 18 or older

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01665326
Contact: Ankit K Desai, MBBS | 919-613-6310 | ankit.desai@duke.edu | |
Contact: Stephanie DeArmey, MHS, PA-C | 919-681-1946 | Stephanie.Dearmey@duke.edu |
United States, North Carolina | |
Duke University Medical Center | Recruiting |
Durham, North Carolina, United States, 27710 | |
Contact: Ankit K Desai, MBBS 919-613-6310 ankit.desai@duke.edu | |
Contact: Stephanie DeArmey, MHS, PA-C 919-681-1946 Stephanie.Dearmey@duke.edu | |
Principal Investigator: Priya S Kishnani, MD |
Principal Investigator: | Priya S Kishnani, MD | Duke University |
Publications of Results:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: | Duke University |
ClinicalTrials.gov Identifier: | NCT01665326 History of Changes |
Other Study ID Numbers: |
Pro00001562 U54NS065768 ( U.S. NIH Grant/Contract ) |
First Posted: | August 15, 2012 Key Record Dates |
Last Update Posted: | July 14, 2017 |
Last Verified: | July 2017 |
Keywords provided by Duke University:
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 |
Additional relevant MeSH terms:
Glycogen Storage Disease Type II 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 Glycogen Storage Disease Carbohydrate Metabolism, Inborn Errors Lysosomal Storage Diseases Metabolic Diseases |