NCT04868578: PROPHECI-PPI

PPI Supplementation to Fight ECtopIc Calcification in PXE

Recruiting now NA Last updated 17 May 2024

What this trial tests

NA trial testing study treatment PPI in Pseudoxanthoma Elasticum in 99 participants. Currently enrolling.

Timeline

13 December 2022

Primary endpoint
13 December 2026

1 September 2027

Quick facts

Lead sponsor	Centre Hospitalier Universitaire de Nice
Phase	NA
Status	Recruiting now
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	double
Primary purpose	treatment
Enrollment	99
Start date	13 December 2022
Primary completion	13 December 2026
Estimated completion	1 September 2027
Sites	2 locations across France

Drugs / interventions tested

• study treatment PPI
• Placebo comparator

Conditions studied

• Pseudoxanthoma Elasticum — all drugs for Pseudoxanthoma Elasticum →

Sponsor

Centre Hospitalier Universitaire de Nice

Who can join

Adults 18 to 65, any sex, with Pseudoxanthoma Elasticum. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Inorganic Pyrophosphate Deficiency Syndromes and Potential Treatments for Pathologic Tissue Calcification.
   Ralph D, van de Wetering K, Uitto J, Li Q. · · 2022 · cited 37× · PMID 35182493 · DOI 10.1016/j.ajpath.2022.01.012
2. Pseudoxanthoma elasticum - Genetics, pathophysiology, and clinical presentation.
   Pfau K, Lengyel I, Ossewaarde-van Norel J, van Leeuwen R, et al · · 2024 · cited 23× · PMID 38815804 · DOI 10.1016/j.preteyeres.2024.101274
3. Therapy of Pseudoxanthoma Elasticum: Current Knowledge and Future Perspectives.
   Stumpf MJ, Schahab N, Nickenig G, Skowasch D, et al · · 2021 · cited 16× · PMID 34944710 · DOI 10.3390/biomedicines9121895
4. The PROPHECI trial: a phase II, double-blind, placebo-controlled, randomized clinical trial for the treatment of pseudoxanthoma elasticum with oral pyrophosphate.
   Clotaire L, Rubera I, Duranton C, Gal J, et al · · 2025 · cited 11× · PMID 39881395 · DOI 10.1186/s13063-024-08666-w
5. A Plasma Pyrophosphate Cutoff Value for Diagnosing Pseudoxanthoma Elasticum.
   Rubera I, Clotaire L, Laurain A, Destere A, et al · · 2024 · cited 7× · PMID 38928212 · DOI 10.3390/ijms25126502
6. New Therapeutics Targeting Arterial Media Calcification: Friend or Foe for Bone Mineralization?
   Van den Branden A, Verhulst A, D'Haese PC, Opdebeeck B. · · 2022 · cited 7× · PMID 35448514 · DOI 10.3390/metabo12040327
7. The Purinergic Nature of Pseudoxanthoma Elasticum.
   Kauffenstein G, Martin L, Le Saux O. · · 2024 · cited 5× · PMID 38392293 · DOI 10.3390/biology13020074
8. Three People With Recurrent Nephrolithiasis and Heterozygous <i>ABCC6</i> Mutations.
   Farrell D, Uribarri J, Pitman TR, Lebwohl M, et al · · 2026 · PMID 41908612 · DOI 10.1016/j.xkme.2026.101271