Pseudoxanthoma Elasticum (PXE) Natural History Biomarkers in PXE Individuals and Their Biological Non-PXE Siblings

Study Overview
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Brief Summary
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This PXE biomarker study aims to characterize the levels of inorganic pyrophosphate (PPi), pyridoxal 5´-phosphate (PLP), and other biomarkers relevant to PXE and ectopic calcification in both PXE patients and their biological siblings who are PXE carriers or normal non-PXE individuals.

Detailed Description
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This non-interventional PXE study is designed to assess differences in circulation levels of selective biomarkers related to PXE and tissue-nonspecific alkaline phosphatase (TNAP) inhibition, between PXE patients, PXE carriers, and non-PXE normal individuals.

Official Title
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An Evaluation of Pseudoxanthoma Elasticum (PXE) Natural History Biomarkers in PXE Individuals and Their Biological Non-PXE Siblings

Conditions
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Pseudoxanthoma Elasticum

Intervention / Treatment
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* Other: Non Interventional


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female participants aged 18 to 75 years Participants (approximately 1 carrier and 1 normal to match proband) Confirmed PXE participants: index PXE/proband with established PXE and ABCC6 mutations identified PXE carrier participants: biological sibling of the PXE index case and confirmed as PXE carrier Non-PXE normal participants: biological sibling of PXE index case and confirmed as non-PXE normal Exclusion Criteria: Unconfirmed ABCC6 mutation status Use of bisphosphonate in the preceding 12 months and during the study Use of Vitamin B6 and/or Vitamin D supplement in the preceding 1 month and during the study (if the total Vitamin B6 supplementation is >5 mg/day) Recent initiation or dose change of Vitamin D and/or multivitamin supplement in the preceding 1 month and during the study Bone fracture within 3 months prior to Screening or active bone disease (excluding osteopenia or osteoporosis) History of hyperparathyroidism History of moderate to severe renal impairment History of hypophosphatasia Known history of uncorrected abnormality in calcium (Ca), phosphate, alkaline phosphatase (ALP) or parathyroid hormone Other significant condition (medical, psychiatric, social, or medication) that, in the judgment of the Investigator, would prevent full participation or would be inappropriate for the study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Confirmed PXE participants<br>Participants who have index PXE/proband with established PXE and ABCC6 mutations identified. | Other: Non Interventional<br>* This is an observational study.<br>|
| PXE carrier participants<br>Participants who are biological siblings of the PXE index case and confirmed as PXE carrier. | Other: Non Interventional<br>* This is an observational study.<br>|
| Non-PXE normal participants<br>Participants who are biological siblings of PXE index case and confirmed as non-PXE normal. | Other: Non Interventional<br>* This is an observational study.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Plasma Levels of Inorganic Pyrophosphate (PPi) | PPi will be assessed by study group and by timepoint where applicable. | Study visit (0 up to 2 hours) | 
| Mean Plasma Levels of Pyridoxal 5´-Phosphate (PLP) | PLP will be assessed by study group and by timepoint where applicable. | Study visit (0 up to 2 hours) | 
| Mean Serum Enzyme Activity Levels of Alkaline Phosphatase (ALP) | ALP will be measured using the standard clinical chemistry assays, by study group and by timepoint where applicable. | Study visit (0 up to 2 hours) | 
| Mean Serum Enzyme Activity Levels of Bone-specific Alkaline Phosphatase (BSAP) | BSAP will be measured using the standard clinical chemistry assays, by study group and by timepoint where applicable. | Study visit (0 hours) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change from Baseline in Plasma Levels of PPi and PLP, by Sex | Blood samples will be assessed by sex group. | Study visit (0 to 2 hours) | 
| Percent Change from Baseline in Serum Enzyme Activity of ALP, by Sex | Blood samples will be assessed by sex group. | Study visit (0 to 2 hours) | 
| Percent Change from Baseline and Variability in Plasma Levels of PPi and PLP | Variability of PPi and PLP will be assessed. | Study visit (0 to 2 hours) | 
| Percent Change from Baseline and Variability in Serum Enzyme Activity of ALP | Variability of ALP will be assessed. | Study visit (0 to 2 hours) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pseudoxanthoma Elasticum, Bone turnover biomarkers, Tissue mineralization biomarkers