Clinical Trial: Determination of CRIM Status and Longitudinal Follow-up of Individuals With Pompe Disease
Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Observational
Official Title: Determination of Cross-Reactive Immunological Material (CRIM) Status and Longitudinal Follow-up of Individuals With Pompe Disease
Brief Summary:
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
Detailed Summary:
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 th
Sponsor: Duke University
Current Primary Outcome: Clinical response to enzyme replacement therapy (ERT) using alglucosidase alfa (Myozyme) [ Time Frame: Up to 10 years ]
Original Primary Outcome: Same as current
Current Secondary Outcome: Response to Immune Tolerance Induction (ITI) [ Time Frame: Up to 10 years ]
Original Secondary Outcome: Response to immunosuppressive therapy [ Time Frame: Up to 10 years ]
Information By: Duke University
Dates:
Date Received: August 13, 2012
Date Started: September 2009
Date Completion: August 2019
Last Updated: August 18, 2016
Last Verified: August 2016