United States Hypophosphatasia Molecular Research Center

Hypophosphatasia Clinical Trial

Official title:

United States Hypophosphatasia Molecular Research Center

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05062629
• Other study ID #: STUDY00001708
• Status: Recruiting
• Start date: August 24, 2021
• Est. completion date: August 1, 2024

Study information

• Verified date: September 2023
• Source: Children's Mercy Hospital Kansas City
• Contact: Eric Rush
• Phone: 816-302-3290
• Email: hpp[@]cmh.edu
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

This study is being done to determine if cryptic alterations exist within or near to the ALPL gene in patients with a clinical diagnosis of hypophosphatasia, but without identifiable alteration on commercial testing. Additionally, the study aims to characterize functional effects of certain variants of uncertain significance in patients with clinical diagnosis of hypophosphatasia.

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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 66
• Est. completion date: August 1, 2024
• Est. primary completion date: August 1, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 1 Month to 120 Years

Eligibility

Inclusion Criteria:

Aim 1-

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

2. 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-

1. Missense variant in ALPL which is interpreted as a variant of uncertain significance by the American College of Medical Genetics Guidelines for Variant Interpretation

2. Variant has been interpreted as pathogenic, likely pathogenic, likely benign, or benign using ex-US interpretation guidelines Exclusion Criteria: Aim 1-

1. History and physical examination incompatible with a diagnosis of hypophosphatasia OR

2. Absence of hypophosphatasemia as measured by age and sex-matched control OR

3. Absence of at least one elevated natural substrate of alkaline phosphatase OR

4. 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

Related Conditions & MeSH terms

• Hypophosphatasia

Intervention

Genetic:
• Whole Genome Sequencing
Whole Genome Sequencing

Locations

Country	Name	City	State
United States	Children's Mercy Hospital	Kansas City	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
Children's Mercy Hospital Kansas City

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Identification of cryptic alterations in the ALPL	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	Finding of alternate diagnoses among the cohort of nominated patients	Finding of alternate diagnoses among the cohort of nominated patients, expanding the differential diagnosis of hypophosphatasemia	3 years

External Links

•   Study Website