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Recruiting NCT04868578

PPI Supplementation to Fight ECtopIc Calcification in PXE

No phase Interventional Pseudoxanthoma Elasticum

For patients and families

In plain language

An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.

What is being studied
The protocol lists: study treatment PPI, Placebo comparator.
Who it may be relevant to
Registry conditions: Pseudoxanthoma Elasticum. Basic parameters: 18 years — 65 years · All.
What needs checking
Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
Where it takes place
France
Next step
Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →

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Official title

Efficacy of PyROphosPHate Supplementation to Fight ECtopIc Calcification in PseudoXanthoma Elasticum - PROPHECI-PPI Study

Overview

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.

Interventions

  • Dietary supplement study treatment PPI
    patient take PPI every day during 12 months
  • Dietary supplement Placebo comparator
    patient take PPI placebo every day during 12 months

Primary outcome measures

  • Arterial calcification score [Time frame: 12 months]
Secondary outcome measures (3)
  • clinical observation of dermatological changes [Time frame: 12 months]
  • clinical observation of ophtalmologic changes [Time frame: 12 Montths]
  • vascular changes [Time frame: 12 months]

Eligibility criteria

Inclusion criteria

  • 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).
  • Efficient contraceptive method in woman of childbearing age at inclusion and during the overall study
  • 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

NON-INCLUSION CRITERIA

  • 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
  • After correcting the hypocalcemia and/or vitamin D deficiency, a participant is again suitable for participation in the trial, as long as the participant meets the inclusion criteria.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation
Randomized
Model
Parallel assignment
Masking
Double blind
Primary purpose
Treatment

Study locations

France · 2 centers
  • Angers Hospital — Angers
  • Nice Hospital — Nice

Publications

  • 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 39881395

Identifiers

NCT: NCT04868578 · 19-APN-01

Primary sources (government registries)

View this study on ClinicalTrials.gov ↗