The TEMP-PREVENT trial: a study protocol for a randomized, double-blind, placebo-controlled clinical trial of etidronate for treatment in young adult patients with pseudoxanthoma elasticum

Abstract

Background: Pseudoxanthoma elasticum (PXE) is a genetic disease with autosomal recessive inheritance, characterized by slowly progressive ectopic calcification in the elastic fibers of the skin, Bruch’s membrane in the retina, and in the arteries. Etidronate was found to be effective in halting the progression of arterial calcification in an earlier trial, including middle-aged patients with PXE with manifest arterial disease. It is uncertain if there are similar effects in young adult patients with PXE. Methods: The TEMP-PREVENT study is a randomized, double-blind, placebo-controlled clinical trial, investigating the effect of 20 mg/kg cyclical etidronate on ectopic calcification in PXE patients of ≥ 18 and ≤ 55 years. The study is conducted at the University Medical Center, Utrecht, the Netherlands. The primary endpoint is the change in arterial calcification volume between baseline and 24 months in the leg arteries and carotid siphons, as measured on low-dose unenhanced Computed Tomography. Secondary endpoints are changes in dermatological, ophthalmological, vascular, laboratory, cognitive and quality of life outcomes/parameters. Recruiting started in April 2023. Results are expected in 2027 and will be dispersed through peer-reviewed journals and international conferences. Discussion: PXE is a rare genetic disease for which there is currently no registered treatment. The TEMP-PREVENT trial is set out to evaluate the effects of etidronate in young adult patients with PXE. Trial registration: The trial is registered at the Dutch Central Committee on Research Involving Human Subjects (CCMO) (registration number: NL75350.041.21), European Union Clinical Trials Register (EudraCT number: 2021–000434-34), and at ClinicalTrials.gov (ID: NCT05832580, registration date 2023-04-14).