- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05062629
United States Hypophosphatasia Molecular Research Center
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Primary Study Objectives:
Determine if cryptic alterations exist within or near to the ALPL gene in patients with clinical diagnosis of hypophosphatasia, but without identifiable pathogenic or likely pathogenic variant on commercial testing.
Secondary Study Objective(s):
Characterize functional effects of variants of uncertain significance in patients with clinical diagnosis of hypophosphatasia
Further characterize the differential diagnosis of hypophosphatasemia in patients with skeletal disease
Study Type
Enrollment (Estimated)
Contacts and Locations
Study Contact
- Name: Eric Rush
- Phone Number: 816-302-3290
- Email: hpp@cmh.edu
Study Locations
-
-
Missouri
-
Kansas City, Missouri, United States, 64108
- Recruiting
- Children's Mercy Hospital
-
Contact:
- Barbara Seuferling
- Phone Number: 816-302-3115
- Email: hpp@cmh.edu
-
Principal Investigator:
- Eric Rush, MD
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Sampling Method
Study Population
Description
Inclusion Criteria:
Aim 1-
Diagnosis of Hypophosphatasia based on clinical features that include
- History consistent with diagnosis of hypophosphatasia AND
- Physical examination findings consistent with a diagnosis of hypophosphatasia AND
- Presence of low serum alkaline phosphatase level for age and sex AND
- Elevation of at least one natural substrate of alkaline phosphatase
- Lack of detection of a variant on molecular analysis of the ALPL gene. When possible, first degree relatives (parents, siblings, or child) will be included for the sole purpose of trio testing. No additional information will be collected on first degree relatives.
Aim 2-
- Missense variant in ALPL which is interpreted as a variant of uncertain significance by the American College of Medical Genetics Guidelines for Variant Interpretation
- Variant has been interpreted as pathogenic, likely pathogenic, likely benign, or benign using ex-US interpretation guidelines
Exclusion Criteria:
Aim 1-
- History and physical examination incompatible with a diagnosis of hypophosphatasia OR
- Absence of hypophosphatasemia as measured by age and sex-matched control OR
- Absence of at least one elevated natural substrate of alkaline phosphatase OR
- Alternate diagnosis which could overlap with signs and symptoms of hypophosphatasia
Aim 2-
1. Inability to express variant in plasmid for residual enzyme and co-transfection analyses
Study Plan
How is the study designed?
Design Details
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Identification of cryptic alterations in the ALPL
Time Frame: 3 years
|
Identification of cryptic alterations in the ALPL, with careful focus on cryptic variants within the 12 exons, intronic variants, and variants in regulatory elements. Characterization of loss of function or dominant negative effect in variants which are considered to be of uncertain clinical significance by American College of Medical Genetics guidelines for variants interpretation such that variants are able to be reclassified into actionable (pathogenic, likely pathogenic) or nonactionable (benign, likely benign) class |
3 years
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Finding of alternate diagnoses among the cohort of nominated patients
Time Frame: 3 years
|
Finding of alternate diagnoses among the cohort of nominated patients, expanding the differential diagnosis of hypophosphatasemia
|
3 years
|
Collaborators and Investigators
Investigators
- Principal Investigator: Eric Rush, Children's Mercy Hospital Kansas City
Publications and helpful links
Helpful Links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
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
- STUDY00001708
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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