The Prevention of Systemic Ectopic Mineralization in Pseudoxanthoma Elasticum

NCT05832580 | Recruiting Phase 3 DMC

• 1 other identifier: 21-552
• Study Type: interventional
• Target: 76
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this randomized clinical trial is to assess the effect of etidronate on ectopic calcification in relatively young patients with Pseudoxanthoma elasticum. The main question it aims to answer are: What is the difference in the arterial calcification scores in the legs and the carotid syphon measured on low-dose CT scan after 24 months of treatment compared to baseline between etidronate and placebo. Participants will be asked to do take etidronate or placebo for 24 months.

Conditions

Pseudoxanthoma Elasticum

Outcome Measures

Primary Outcomes (1)

• Arterial calcification

  The difference in arterial calcification volume measured (uL) on CT-scans between the etidronate and placebo group 24 months.

  24 months.

Secondary Outcomes (29)

• Ophtalmology: Visual acuity

  24 months.

• Ophtalmology: Contrast sensitivity.

  24 months.

• Ophtalmology: Reflectivity of Bruch's membrane

  24 months.

• Ophtalmology: Length of angioid streaks.

  24 months.

• Ophtalmology: Area of angioid streaks.

  24 months.

Study Arms (2)

Etidronate

EXPERIMENTAL

Daily dosis of 20mg/kg of etidronate in a cyclical regimen of 2 weeks on and 10 weeks off, for a total of 24 months.

Drug: Etidronate

Placebo

PLACEBO COMPARATOR

Daily dosis of placebo in a cyclical regimen of 2 weeks on and 10 weeks off, for a total of 24 months.

Drug: Placebo

Interventions

Etidronate DRUG

Etidronate in capsules of 200 mg or 400 mg.

Etidronate

Placebo DRUG

Placebo in similar capsules

Placebo

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• In order to be eligible to participate in this study, a subject must meet all of the following criteria:
• \. Be between 18 years and 50 years.
• \. Have a definitive diagnosis of PXE according to the Plomp criteria, which confirm a diagnosis of PXE when at least two (or more) criteria not belonging to the same category (skin, eye, genetic) are met:
• Skin
• Yellowish papules and/or plaques on the lateral side of the neck and/or flexural areas of the body or
• Increase of morphologically altered elastin with fragmentation, clumping and calcification of elastic fibers in a skin biopsy taken.
• Eye
• Peau d'orange of the retina or
• One or more angioid streaks (AS), each at least as long as one disk diameter. When in doubt, fluorescein or indocyanine green angiography of the fundus is needed for confirmation.
• Genetics
• A pathogenic mutation of both alleles of the ABCC6 gene or
• A first-degree relative (parent, sibling or child) who meets independently the diagnostic criteria for definitive PXE
• \. Fertile women must take adequate anticonception.

You may not qualify if:

• A potential subject who meets any of the following criteria will be excluded from participation in this study:
• Patients that are unable or unwilling to sign for informed consent.
• Pregnant, lactating, or fertile women who might wish to become pregnant within three years.\*\*
• Patients with an estimated glomerular filtration rate below 30 ml/min/1.73m2 according to the CKD-EPI equation.31
• Patients with a known abnormality of the oesophagus that would interfere with passage of the drug (e.g. oesophagus stenosis).
• Patients with chronic diarrhoea (\> 1 month).
• Patients with known osteomalacia;
• Patients with hypocalcaemia (calcium \<2.20 mmol/L corrected for albumin)\*.
• Patients with a vitamin D deficiency (\<35 nmol/L)\*.
• Patients that used a bisphosphonate in the last 5 years.
• Patients with known sensitivity to etidronate.
• Any other medical or social condition that, at the discretion of the Principal Investigator, might put the subject at risk of harm during the study or might adversely affect the interpretation of the study data.
• Subjects that become pregnant during the trial will be excluded from further participation.

Sponsors & Collaborators

• UMC Utrecht: lead

Study Sites (1)

University Medical Center Utrecht

Utrecht, 3584 CX, Netherlands

RECRUITING

Related Publications (1)

• Harmsen IM, Haverkamp M, van den Beukel TC, Kok M, de Jong PA, van Valen E, van Leeuwen R, Norel JO, Spiering W. 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. Trials. 2025 Oct 23;26(1):431. doi: 10.1186/s13063-025-09064-6.

  PMID: 41131563 DERIVED

MeSH Terms

Conditions

Pseudoxanthoma Elasticum

Interventions

Etidronic Acid

Condition Hierarchy (Ancestors)

Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Hemorrhagic Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Skin Abnormalities; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Skin Diseases, Genetic; Genetic Diseases, Inborn; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Skin Diseases

Intervention Hierarchy (Ancestors)

Diphosphonates; Organophosphonates; Organophosphorus Compounds; Organic Chemicals

Central Study Contacts

Wilko Spiering, MD, PhD

CONTACT

+ 88 755 5555; w.spiering@umcutrecht.nl

Iris Harmsen, MD

CONTACT

+ 88 755 5555; i.m.harmsen@umcutrecht.nl

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, PhD

Study Record Dates

• First Submitted: March 14, 2023
• First Posted: April 27, 2023
• Study Start: April 26, 2023
• Primary Completion (Estimated): March 29, 2027
• Study Completion (Estimated): April 29, 2027
• Last Updated: April 27, 2023

Record last verified: 2023-04

Locations

NL (1)