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

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2014 by Duke University
Sponsor:
Collaborators:
Rare Diseases Clinical Research Network
Information provided by (Responsible Party):
Duke University
ClinicalTrials.gov Identifier:
NCT01665326
First received: August 13, 2012
Last updated: October 1, 2014
Last verified: October 2014

August 13, 2012
October 1, 2014
September 2009
August 2019   (final data collection date for primary outcome measure)
Clinical response to enzyme replacement therapy (ERT) using alglucosidase alfa (Myozyme) [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]
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.
Same as current
Complete list of historical versions of study NCT01665326 on ClinicalTrials.gov Archive Site
Response to Immune Tolerance Induction (ITI) [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]
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.
Response to immunosuppressive therapy [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]
Medical records will be tracked for up to 10 years to follow clinical response to immunosuppressive therapy 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.
Not Provided
Not Provided
 
Determination of CRIM Status and Longitudinal Follow-up of Individuals With Pompe Disease
Determination of Cross-Reactive Immunological Material (CRIM) Status and Longitudinal Follow-up of Individuals With Pompe Disease

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:

  1. To determine and correlate Cross-Reactive Immunological Material (CRIM) status with the GAA gene mutations found on these patients
  2. 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
  3. To explore the clinical treatment response and natural history of CRIM-positive and CRIM-negative Pompe disease patients with and without immune modulation
  4. To investigate the role of immune response to treatment

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:

  1. To determine and correlate Cross-Reactive Immunological Material (CRIM) status with the GAA gene mutations found on these patients
  2. 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
  3. To explore the clinical treatment response and natural history of CRIM-positive and CRIM-negative Pompe disease patients with and without immune modulation
  4. To investigate the role of immune response to treatment
Observational
Observational Model: Cohort
Time Perspective: Prospective
Not Provided
Not Provided
Non-Probability Sample

Study subjects will be babies/children 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.
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).
Infantile Pompe disease
Individuals with a confirmed diagnosis of Infantile Pompe disease
Intervention: Other: Observational

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
300
August 2019
August 2019   (final data collection date for primary outcome measure)

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
Both
up to 18 Years
No
Contact: Katie Sheets, MS, CGC 919-681-1984 Katie.Sheets@duke.edu
Contact: Stephanie DeArmey, MHS, PA-C 919-681-1946 Stephanie.Dearmey@duke.edu
United States
 
NCT01665326
Pro00001562, U54NS065768
Yes
Duke University
Duke University
  • Rare Diseases Clinical Research Network
  • National Center for Advancing Translational Science (NCATS)
  • National Institute of Neurological Disorders and Stroke (NINDS)
  • National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Principal Investigator: Priya S Kishnani, MD Duke University
Duke University
October 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP