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.

Eligibility

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.