PPI Supplementation to Fight ECtopIc Calcification in PXE
PROPHECI-PPI
Efficacy of PyROphosPHate Supplementation to Fight ECtopIc Calcification in PseudoXanthoma Elasticum - PROPHECI-PPI Study
1 other identifier
interventional
99
1 country
2
Brief Summary
Pseudoxanthoma elasticum (PXE) is a rare inherited metabolic disorder (OMIM 264800, frequency 1/25000) characterized by progressive ectopic calcification of connective tissues. PXE mainly affects the skin (inesthetic papules and plaques in the skin folds), the retina (central blindness), the vasculature (peripheral arterial occlusive disease and stroke) and the renal system (renal lithiasis) in adulthood. Although rarely, early lethal forms have been reported. This chronic and highly disabling condition results from a loss of function of the gene encoding for the ABCC6 membrane transporter primarily expressed in the hepatocytes and renal tubular cells. Recently, it has been reported that PXE was characterized by a 50-60% decrease in the plasma level of inorganic pyrophosphate (PPi), a major physiological anti-calcifying factor. PXE is an incurable disease which therapeutic options are limited to symptomatic treatments to stem the devastating effect of the ectopic calcifications. Recently, encouraging proof of concept studies with animals PXE models and healthy volunteers have shown that, contrary to what was initially reported and thought, the oral administration of PPi salts are able to increase PPi plasma levels, opening up new therapeutic perspectives in PXE. Therefore, we propose to perform the first Phase II randomized controlled trial (RCT) to evaluate the safety and efficacy of a daily and oral administration of PPi salts against placebo in PXE patients.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for not_applicable
Started Dec 2022
Longer than P75 for not_applicable
2 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
March 30, 2021
CompletedFirst Posted
Study publicly available on registry
May 3, 2021
CompletedStudy Start
First participant enrolled
December 13, 2022
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 13, 2026
ExpectedStudy Completion
Last participant's last visit for all outcomes
September 1, 2027
May 17, 2024
May 1, 2024
4 years
March 30, 2021
May 16, 2024
Conditions
Outcome Measures
Primary Outcomes (1)
Arterial calcification score
Using manufacturer dedicated software, the investigator, will determine the calcification score from CT images according to the validated Agatston score method. A threshold of 130 Hounsfield Units for calcium detection will be used for the study. Voxels above this threshold representing arterial wall calcifications will be manually identified and selected by the observer on the CT image. Calcifications mass in the studied arterial segments will be analyzed and quantified. The length and antero-posterior mean diameter of each arterial segment will be determined for further normalization of the calcification score to the arterial wall surface (data expressed as HU/mm2 of arterial surface). The intraclass correlation and Bland-Altman coefficient for inter-observer reliability of the total peripheral artery calcium mass measurement will be determined by scoring 10 random scans by two independent investigators.
12 months
Secondary Outcomes (3)
clinical observation of dermatological changes
12 months
clinical observation of ophtalmologic changes
12 Montths
vascular changes
12 months
Study Arms (2)
PPI
EXPERIMENTALthe patient take PPI caps
PPI placebo
PLACEBO COMPARATORThe patient take PPI placebo
Interventions
Eligibility Criteria
You may qualify if:
- Patients (\>18 years and \<65 years), men and women, presenting a clinically and biologically authenticated PXE (genotype + phenotype) according to the international diagnostic criteria (26).
- Patient affiliated to a social security insurance
- Signed informed consent
- Patient without acute complication linked or not to the pathology at the time of the study
- Renal insufficiency (i.e. defined by a renal clearance \<30ml / min / 1.73 m²)
- Patients with osteomalacia
- Patients with chronic diarrhea (\> 1 month)
- Pregnancy, lactating or fertile women who may wish to become pregnant within three years.
- Any other medical condition that may be considered in the opinion of the Principal Investigator.
- Use of bisphosphonate during last 5 years.
- Hypocalcemia (calcium \<2.20 mmol/L and ionized calcium \<1.15 mmol/L) \*.
- Vitamin D deficiency \<35 nmol/L \*
- Enrollment in another inteventional clinical trial which could interfere with the present study
- patients (\>18 years) protected by law
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (2)
Angers Hospital
Angers, 49000, France
Nice Hospital
Nice, 06000, France
Related Publications (1)
Clotaire L, Rubera I, Duranton C, Gal J, Chamorey E, Humeau H, Yamani S, Chiaverini C, Willoteaux S, Padovani B, Mourozeau L, Mainguy A, Baillif S, Martin L, Leftheriotis G. The PROPHECI trial: a phase II, double-blind, placebo-controlled, randomized clinical trial for the treatment of pseudoxanthoma elasticum with oral pyrophosphate. Trials. 2025 Jan 29;26(1):30. doi: 10.1186/s13063-024-08666-w.
PMID: 39881395DERIVED
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- not applicable
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Who Masked
- PARTICIPANT, INVESTIGATOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
March 30, 2021
First Posted
May 3, 2021
Study Start
December 13, 2022
Primary Completion (Estimated)
December 13, 2026
Study Completion (Estimated)
September 1, 2027
Last Updated
May 17, 2024
Record last verified: 2024-05
Data Sharing
- IPD Sharing
- Will not share