Grönblad-Strandberg syndrome Pseudoxantoma elasticum
Conditions
Interventions
Etidronate versus placebo
Sponsors
Universitair Medisch Centrum Utrecht
Eligibility
Age
18 Years to 64 Years
Inclusion criteria
Inclusion criteria: In order to be eligible to participate in this study, a subject must meet all of the following criteria: - Be between 18 years and 55 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: 1. Skin a. Yellowish papules and/or plaques on the lateral side of the neck and/or flexural areas of the body or b. Increase of morphologically altered elastin with fragmentation, clumping and calcification of elastic fibers in a skin biopsy taken. 2. Eye a. Peau d'orange of the retina or b. 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 a. A pathogenic mutation of both alleles of the ABCC6 gene or b. A first-degree relative (parent, sibling or child) who meets independently the diagnostic criteria for definitive PXE
Exclusion criteria
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. 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 osteomalacia. 7. Patients with hypocalcaemia (calcium
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Arterial calcification in the legs and carotid syphons measured on low dose Ct scan. | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. To determine the effect of 24 months of treatment with etidronate on functional ophthalmological measurements, such as visual acuity and contrast sensitivity compared to placebo. 2. To determine if 24 months of treatment with etidronate halts the progression of normalized reflectivity in Bruch*s membrane as measured with SD-optical coherence tomography, compared to placebo. 3. To determine the effect of 24 months of treatment with etidronate on structural ophthalmological measurements, on fundus photography, (infrared (IR) and autofluorescence (FAF)) and OCT-angiography (OCTA). 4. To determine if 24 months of treatment with etidronate affects the intracranial velocity pulsatility index as measured with MRI. 5. To determine if 24 months of treatment with etidronate halts the progression of elastin degradation and of calcification in the skin in dermatological observation of skin biopsies, compared to placebo. 6. To determine the effect of 24 months of treatment with etidronate on inorganic pyrophosphate an desmosine compared to placebo. 7. To determine if 24 months of treatment with etidronate halts leads to changes in vascular measurements (carotid intima-media thickness, pulse wave velocity on ultrasound, ankle brachial index, 6 minute walking test and WELCH questionnaire) compared to placebo. 8. To determine if 24 months of treatment with etidronate leads to decreased occurrence of major adverse cardiovascular events (stroke, TIA, myocardial infarction or cardiovascular death) compared to placebo. 9. To determine if 24 months of treatment with etidronate leads to improved reported quality of life amd physical functioning, as measured with the EQ-5D, PROMIS 10, PROMIS PF and USER P compared to placebo. 10. To determine if 24 months of treatment with etidronate leads to better results on cognitive tests compared to placebo. 11. To determine if 24 months of treatment with etidronate leads to observed differences in safety measures: cha | — |
Countries
Netherlands
Outcome results
None listed