- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03812042
Screening of Lysosomal Storage Disorders Diseases in Minority Groups
Enzymatic and Genotypic Screening of Lysosomal Storage Diseases in Minority Groups
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Lysosomes are small, cytoplasmic organelles that contain several acid hydrolase enzymes. These enzymes break down foreign materials and cellular debris allowing the lysosomes to act as recycling centers for the cells. Following DNA transcription, lysosomal enzymes are produced in the endoplasmic reticulum and targeted to lysosomes by specific recognition markers. If one of the enzymes is absent or if its function is diminished due to either an altered amino acid sequence of the protein or defective intracellular trafficking, the macromolecules metabolized by the specific enzyme will gradually accumulate in the lysosomes. Abnormal substrate storage leads to cellular dysfunction followed by cell death ultimately manifesting as tissue damage and organ failure.
More than 50 metabolic disorders resulting from defective lysosomal enzyme function have been described and are classified as lysosomal storage disorders (LSDs). Although individually uncommon (less than 1 in 100,000), the combined incidence of this group of genetic disorders is about 1 in 5,000 to 1 in 10,000. The prevalence might be even higher than predicted due to undiagnosed instances or misdiagnosis of milder cases.
Most of LSDs are inherited in an autosomal recessive manner except two disorders: Fabry disease and Hunter syndrome, which are X chromosome linked. Two healthy carriers of the same autosomal recessive disease may have an affected child. Usually the carriers are unaware of their carrier status prior to screening or until they have a sick child. These disorders are more common in communities with high consanguinity and where cousin marriages are allowed. In the case of X-linked diseases, the mutant gene is passed down from one generation to the next one in a specific way. If a male has an abnormal copy of the specific gene, he will show the typical presentation of the disease. If a woman has an abnormal copy of the specific gene, she may develop some milder symptoms of the disease due to random X- inactivation.
Screening for LSDs is performed by measuring enzymatic activity in peripheral blood. The most cost effective and convenient way is to use dried filter paper blood spots. A positive screening result has to be followed by a confirmatory enzymatic testing using white blood cells, plasma or cultured skin fibroblasts and/or DNA mutation analysis. The importance of screening for LSDs has been recognized by several state governments as these tests are being included in many newborn screening programs. Although newborn screening helps to identify patients early on, there is still an unmet need for population screening and for identifying patients with reversible tissue damage. LSDs cause serious and progressive problems with multiple body systems. Therapy is available and is promising in most cases. Importantly, patients with LSDs require thorough management plans for their complex health issues.
Study Type
Enrollment (Anticipated)
Contacts and Locations
Study Locations
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Virginia
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Fairfax, Virginia, United States, 22030
- LDRTC
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Child
- Adult
- Older Adult
Accepts Healthy Volunteers
Genders Eligible for Study
Sampling Method
Study Population
Description
Inclusion Criteria:
To be enrolled in this study the subject must meet the following (inclusion) criteria:
- Subject is greater than or equal to 1 day of age and less than or equal to 100 years of age
- Subject is managed by a physician in the Washington, D.C and Richmond, VA metro area
- Subject is getting blood work as part of standard clinical care and there is at least 60 uL blood remained in a tube after all clinical tests were run
Exclusion Criteria:
subjects must not meet any of the following (exclusion) criteria:
- Absolute contraindication for blood drawing
- Subject cannot be traced back by the referring physician upon a positive screening result
Study Plan
How is the study designed?
Design Details
- Observational Models: Ecologic or Community
- Time Perspectives: Prospective
Cohorts and Interventions
Group / Cohort |
Intervention / Treatment |
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Screen population
The study population will comprise of patients of healthcare institutions in the Washington, D.C. metro area including but not limited to hospitals, clinics, and doctor's offices.
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Enzyme assay and molecular sequencing on relevant samples conducted from left over blood samples
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Enzyme activity analysis to identify subjects with Lysosomal storage disorders
Time Frame: 5 years
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To identify patients with LSDs using enzymatic activity specific to individual lysosomal storage disorders using left-over blood of blood samples collected as part of standard clinical care.
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5 years
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Genotypic analysis of subjects with abnormal enzyme activity
Time Frame: 5 years
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Samples from subjects with abnormally low enzyme activity will be used for targeted sequencing analysis to diagnose any pathologic mutations.
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5 years
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Collaborators and Investigators
Investigators
- Principal Investigator: Margarita M Ivanova, PhD, LDRTC
- Principal Investigator: Ozlem Goker-Alpan, MD, LDRTC
Publications and helpful links
Helpful Links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 16-LDRTC-04
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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