Preventing calcification in patients with Pseudoxanthoma Elasticum

The Prevention of Systemic Ectopic Mineralization in Pseudoxanthoma Elasticum

This study is testing if a medication called etidronate can help young adults with Pseudoxanthoma Elasticum reduce harmful calcification in their arteries over two years.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 76 (estimated)
• Ages: 18 Years to 50 Years
• Sex: All
• Sponsor: UMC Utrecht (Academic / other)
• Drugs / interventions: radiation
• Locations: 1 site (Utrecht)
• Trial ID: NCT05832580 on ClinicalTrials.gov

What this trial studies

This clinical trial aims to evaluate the effectiveness of etidronate in reducing ectopic calcification in young adults diagnosed with Pseudoxanthoma Elasticum (PXE). Participants aged 18 to 50 will be randomly assigned to receive either etidronate or a placebo for a duration of 24 months. The primary outcome will be measured by comparing arterial calcification scores in the legs and carotid syphon using low-dose CT scans before and after treatment. The study seeks to address the underlying calcification issues associated with PXE, which can lead to severe complications such as visual impairment and cardiovascular problems.

Who should consider this trial

Good fit: Ideal candidates for this study are individuals aged 18 to 50 with a confirmed diagnosis of Pseudoxanthoma Elasticum.

Not a fit: Patients outside the age range of 18 to 50 or those without a definitive diagnosis of Pseudoxanthoma Elasticum will not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly reduce calcification-related complications in patients with Pseudoxanthoma Elasticum.

How similar studies have performed: Previous studies have shown promising results with etidronate in related conditions, suggesting potential success for this approach in PXE.

Eligibility criteria

Inclusion Criteria:

In order to be eligible to participate in this study, a subject must meet all of the following criteria:

* 1\. Be between 18 years and 50 years.
* 2\. 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:

  1. Skin

     1. Yellowish papules and/or plaques on the lateral side of the neck and/or flexural areas of the body or
     2. Increase of morphologically altered elastin with fragmentation, clumping and calcification of elastic fibers in a skin biopsy taken.
  2. Eye

     1. Peau d'orange of the retina or
     2. 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.
  3. Genetics

     1. A pathogenic mutation of both alleles of the ABCC6 gene or
     2. A first-degree relative (parent, sibling or child) who meets independently the diagnostic criteria for definitive PXE
* 3\. Fertile women must take adequate anticonception.

Exclusion Criteria:

A potential subject who meets any of the following criteria will be excluded from participation in this study:

1. Patients that are unable or unwilling to sign for informed consent.
2. Pregnant, lactating, or fertile women who might wish to become pregnant within three years.\*\*
3. Patients with an estimated glomerular filtration rate below 30 ml/min/1.73m2 according to the CKD-EPI equation.31
4. Patients with a known abnormality of the oesophagus that would interfere with passage of the drug (e.g. oesophagus stenosis).
5. Patients with chronic diarrhoea (\> 1 month).
6. Patients with known osteomalacia;
7. Patients with hypocalcaemia (calcium \<2.20 mmol/L corrected for albumin)\*.
8. Patients with a vitamin D deficiency (\<35 nmol/L)\*.
9. Patients that used a bisphosphonate in the last 5 years.
10. Patients with known sensitivity to etidronate.
11. 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.

    * After correction a patient is again suitable for participation, as long as inclusion criteria are met (more information in paragraph 7.3.3).

      * Subjects that become pregnant during the trial will be excluded from further participation.

Where this trial is running

Utrecht

• University Medical Center Utrecht — Utrecht, Netherlands (Recruiting)

Study contacts

• Study coordinator: Wilko Spiering, MD, PhD

Conditions Pseudoxanthoma Elasticum