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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
  Purpose

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

Condition Intervention
Pompe Disease
Other: Observational

Study Type: Observational
Study Design: 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

Resource links provided by NLM:


Further study details as provided by Duke University:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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.


Estimated Enrollment: 300
Study Start Date: September 2009
Estimated Study Completion Date: August 2019
Estimated Primary Completion Date: August 2019 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
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).

Detailed Description:

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
  Eligibility

Ages Eligible for Study:   up to 18 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

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.
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01665326

Contacts
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

Locations
United States, North Carolina
Duke University Medical Center Recruiting
Durham, North Carolina, United States, 27710
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   
Principal Investigator: Priya S Kishnani, MD         
Sponsors and Collaborators
Duke University
Rare Diseases Clinical Research Network
Investigators
Principal Investigator: Priya S Kishnani, MD Duke University
  More Information

Publications:
Responsible Party: Duke University
ClinicalTrials.gov Identifier: NCT01665326     History of Changes
Other Study ID Numbers: Pro00001562, U54NS065768
Study First Received: August 13, 2012
Last Updated: October 1, 2014
Health Authority: United States: Institutional Review Board

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
Brain Diseases
Brain Diseases, Metabolic
Brain Diseases, Metabolic, Inborn
Carbohydrate Metabolism, Inborn Errors
Central Nervous System Diseases
Genetic Diseases, Inborn
Glycogen Storage Disease
Lysosomal Storage Diseases
Lysosomal Storage Diseases, Nervous System
Metabolic Diseases
Metabolism, Inborn Errors
Nervous System Diseases

ClinicalTrials.gov processed this record on November 20, 2014