View clinical trials related to Pseudoxanthoma Elasticum.
Filter by:This PXE biomarker study aims to characterize the levels of inorganic pyrophosphate (PPi), pyridoxal 5´-phosphate (PLP), and other biomarkers relevant to PXE and ectopic calcification in both PXE patients and their biological siblings who are PXE carriers or normal non-PXE individuals.
Pseudoxanthoma elasticum (PXE) is a rare inherited metabolic disorder (OMIM 264800, frequency 1/25000) characterized by progressive ectopic calcification of connective tissues. PXE mainly affects the skin (inesthetic papules and plaques in the skin folds), the retina (central blindness), the vasculature (peripheral arterial occlusive disease and stroke) and the renal system (renal lithiasis) in adulthood. Although rarely, early lethal forms have been reported. This chronic and highly disabling condition results from a loss of function of the gene encoding for the ABCC6 membrane transporter primarily expressed in the hepatocytes and renal tubular cells. Recently, it has been reported that PXE was characterized by a 50-60% decrease in the plasma level of inorganic pyrophosphate (PPi), a major physiological anti-calcifying factor. PXE is an incurable disease which therapeutic options are limited to symptomatic treatments to stem the devastating effect of the ectopic calcifications. Recently, encouraging proof of concept studies with animals PXE models and healthy volunteers have shown that, contrary to what was initially reported and thought, the oral administration of PPi salts are able to increase PPi plasma levels, opening up new therapeutic perspectives in PXE. Therefore, we propose to perform the first Phase II randomized controlled trial (RCT) to evaluate the safety and efficacy of a daily and oral administration of PPi salts against placebo in PXE patients.
Protocol code and version: FIM-PXE-2016-01 Version 1.4 Trial title: "Response to oral lansoprazole of inorganic pyrophosphate levels in patients with Grönblad- Stranberg disease (Pseudoxanthoma Elasticum)" Trial design: Double-blind, placebo-controlled, randomised, two-stage crossover clinical trial, with each patient serving as their own control and reducing the number of patients to confirm our hypothesis. Principal Investigator: Dr. Pedro Valdivielso Felices Participating centres Virgen de la Victoria's Universitary Hospital in Malaga and Virgen de la Macarena's Universitary Hospital in Seville. Duration of the trial: 12 months Expected start date: December 2019 Objectives: Principal:To verify the changes in plasma PPi, and the main molecules that regulate it (NPP1-3, TNAP) after oral administration of lansoprazole in patients diagnosed with PXE. Description of treatment: Selection:20 patients who meet all the criteria for inclusion and none for exclusion. Randomisation and 1st stage: Patients will receive lansoprazole 30mg/day or their placebo for 8 weeks. Wash-out: After 8 weeks, all treatment will be suspended for 15 days. 2nd stage (crossed): Treatment is crossed, each patient serves as his or her own control. Evaluation variables: 1. Date of Birth 2. Sex. 3. Physical examination (anthropometry and vital signs) 4. Date of first symptom. 5. Date of final diagnosis 6. Ocular affectation (orange peel skin, complete striae angioides, lucentis, corrected visual acuity, cataracts, intraocular pressure, fundus (vascular flow, optic nerve drusen, retinal atrophy, neovascular membranes, macular thickness, colloid thickness). 7. Skin affectation (yellowish papules or plaques on the side of the neck or other areas of flexure and lax skin). 8. Vascular affectation (intermittent claudication clinic, angina and/or episode of acute myocardial infarction and/or non-embolic ischemic stroke, surgical or percutaneous revascularisation, cardiac murmur,10.) 9. History of renal lithiasis, arterial hypertension, diabetes mellitus, treatments, smoking and dyslipidemia. 10. Specific biochemical variables: Inorganic pyrophosphate (IPP) NPP1 and NPP2.3: activity and mass concentration of the enzyme Non-specific tissue alkaline phosphatase (NTAP) and PHA. Osteocalcin: To check possible side effects on bone metabolism. 5'-Nucleotidas General analytical parameters (haemoglobin, haematocrit, MVC, MHC, platelets, neutrophils, prothrombin activity, TPTA, thrombin time, ferritin, PCR, glycaemia, urea, creatinine, cholesterol, triglycerides, HDL cholesterol, LDL cholesterol, uric acid, calcium, phosphorus, alkaline phosphatase, PTH). By means of routine clinical laboratory techniques. Number of patients: TOTAL : 20 patients(Competitive recruitment)
Pyrophosphate is an endogenous, non-toxic metabolite inhibiting soft tissue calcification. The aim of our study is to find optimal dosing and safety of oral disodium-PPi (Na2H2PPi). Absorption curves (pharmacokinetics), AUC0-t, Cmax and Tmax for PPi and phosphate will be provided for healthy controls and PXE-patients both fasting and with standard meal intake.
This study aims to demonstrate a potential association between gut microbiota composition, plasma levels of various forms of vitamin K, and severity of clinical manifestations of Pseudoxanthoma Elasticum (PXE).
Generalized arterial calcification of infancy (GACI) is an ultra-rare disorder with an estimated birth prevalence of around 1 in 400,000.1 GACI is generally fatal before birth or within the first six months after birth. The cause of death is frequently myocardial infarction or stroke. GACI is strongly associated with inactivating mutations in ectonucleotide pyrophosphate/ phosphodiesterase 1 (ENPP1). Many patients with GACI, including some without an ENPP1 mutation also present with mutations in adenosine triphosphate binding cassette transporter protein subfamily C member 6 (ABCC6). Autosomal recessive hypophosphatemic rickets type 2 (ARHR2) and pseudoxanthoma elasticum (PXE) are believed to be closely related to GACI. ARHR2 is caused by mutations in the ENPP1 gene and PXE is caused by mutations in the ABCC6 gene, with both being observed among patients with GACI. The natural history of GACI and in particular its long term morbidity and mortality are poorly understood. The primary objective of this study is to characterize overall survival among patients with GACI, over time from birth.
Our objective is to obtain human induced pluripotent stem cells from urine samples of PXE patients for further proteomic and metabolomic studies and treatment screening.
The investigators hypothesize is that in PXE patients, low grade chronic inflammation could preceed the molecular and the clinical calcification process.
The purpose of this study is to determine whether Aflibercept (Eylea) is effective in the treatment of choroidal neovascularization and fibrovascular proliferation in patients with pseudoxanthoma elasticum (PXE) in terms of preservation or improvement of visual acuity.
Pseudoxanthoma elasticum (PXE) is a rare multisystem disorder of autosomal recessive inheritance (OMIM# 264800) and an estimated prevalence between 1:25.000 and 1:100.000. PXE is characterized by calcification and fragmentation of connective tissue rich in elastic fibers. Due to its high content of elastic fibers, Bruch Membrane in eyes of patients affected by PXE becomes thickened and calcified. The ocular phenotype is characterized by angioid streaks and peau d'orange but also choroidal neovascularizations and chorioretinal atrophy thereby in part mimicking the phenotype of age-related macular degeneration. The disease is due to mutations of the ABCC6-gene coding for a transmembrane protein which is mainly expressed in the liver and kidney. It is hypothesized that ABCC6 is involved in the excretion of a yet unknown factor from the liver which inhibits systemic calcification. In animal models several candidates for this factor have been identified but direct evidence for such a factor in patients with PXE is still missing. The primary purpose of this study is to further investigate the ocular phenotype of patients with PXE using multimodal imaging and functional testing to delineate the impact of Bruch membrane pathology on the eye. Furthermore, possible systemic anti-calcification factors, as well as associations with the vascular alterations are investigated to gain more insights into the pathogenesis of PXE..