The prevention of systemic ectopic mineralization in pseudoxanthoma elasticum - TEMP-PREVENT trial - (Treatment of Ectopic Mineralization in Pseudoxanthoma elasticum) A placebo controlled, double-blind randomized trial evalueating the effect of etidronate in young patients with pseudoxanthoma elasticum.

Universitair Medisch Centrum Utrecht1 个研究点分布在 1 个国家目标入组 76 人2024年10月28日

概览

阶段: 3 期
干预措施: 未指定
疾病 / 适应症: 未指定
发起方: Universitair Medisch Centrum Utrecht
入组人数: 76
试验地点: 1
主要终点: The main study endpoint will be the percentage change in arterial calcification in carotid siphon and legs measured with low-dose CT scan after 24 months of treatment with etidronate compared with placebo.
状态: 进行中（未招募）
最后更新: 去年

概览研究者入排标准结局指标研究点相似试验

概览

简要总结

To determine if 24 months of treatment with etidronate halts the progression of arterial calcification in the legs and carotid siphons.

注册库

euclinicaltrials.eu

开始日期

2024年10月28日

结束日期

待定

最后更新

去年

研究类型

Interventional clinical trial of medicinal product

研究者

发起方

Universitair Medisch Centrum Utrecht

责任方

Principal Investigator

主要研究者

Wilko Spiering

Scientific

Universitair Medisch Centrum Utrecht

入排标准

入选标准

•Be between 18 years and 55 years
•Have a definitive diagnosis of PXE according to the Plomp criteria27, 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 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.
•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.
•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
•Fertile women must take adequate anticonception.

排除标准

•Patients that are unable or unwilling to sign for informed consent.
•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.
•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
•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)*. *After correction a patient is again suitable for participation, as long as inclusion criteria are met
•Patients with a vitamin D deficiency (<35 nmol/L)*. *After correction a patient is again suitable for participation, as long as inclusion criteria are met

结局指标

主要结局

The main study endpoint will be the percentage change in arterial calcification in carotid siphon and legs measured with low-dose CT scan after 24 months of treatment with etidronate compared with placebo.

次要结局

To determine the effect of 24 months of treatment with etidronate on functional ophthalmological measurements, such as visual compared to placebo.
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.
To determine the effect of 24 months of treatment with etidronate on structural ophthalmological measurements on fundus photography (infrared and autofluorescence and OCT-angiography).
7T Magnetic resonance imaging will be used to determine if treatment with etidronate halts the progression of increased pulsatility index of the intracranial carotid arteries and middle cerebral arteries.
To determine if treatment with etidronate halts the progression of elastin degradation and of calcification in the skin in skin biopsies, compared to placebo.
To determine if treatment with etidronate leads to increased levels of plasma levels of inorganic pyrophosphate compared to placebo.
To determine if treatment with etidronate halts the progression of systemic elastin degradation products, as measured via plasma levels of desmosin, compared to placebo.
To determine if treatment with etidronate halts the progression of arterial calcification in legs and siphons, as measured with computed tomography, compared to placebo.
To determine if treatment with etidronate halts the progression of increased carotid intima media thickness, as measured with ultrasound with a linear array transducer, compared to placebo.
To determine if treatment with etidronate halts the progression of arterial stiffness, as measured by pulse wave analysis and velocity using a Doppler-ultrasound, compared to placebo.
To determine if treatment with etidronate halts progression of peripheral artery disease measured by the ankle brachial index, the WELCH questionnaire and the six-minute walking test.
To determine if treatment with etidronate leads to decreased occurrence of major cardiovascular events (stroke, TIA, myocardial infarction or cardiovascular death) events compared to placebo.
To determine if treatment with etidronate leads to improved reported quality of life and self reported health, as measured with the EQ-5D, PROMIS 10, PROMIS PF, USER P compared to placebo.
To determine if 24 months of treatment with etidronate leads to better results on cognitive outcomes, compared with placebo
To determine if treatment with etidronate leads to observed differences in safety measures: changes in plasma calcium, phosphate, ASAT, ALAT, eGFR measured via laboratory assessment, and number of anti-VEGF injections used