Magnesium Supplements In The Treatment Of Pseudoxanthoma Elasticum (PXE)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 44
- 试验地点
- 1
- 主要终点
- Von Kossa Staining Per Unit Area of Dermis
研究概览
简要总结
The purpose of this study is to evaluate the effectiveness of magnesium oxide supplements on the reversal of calcium deposits in the skin, and the yellow bumps and folds of skin in subjects with pseudoxanthoma elasticum (PXE). Magnesium oxide is a dietary supplement that has been shown in some research to reduce these calcium deposits. This study consists of two parts. The first part is a year-long, double-blind, placebo-controlled study. Part two is an open-label, year-long study. In Part 1, qualified subjects will be randomized to receive either magnesium oxide supplements or placebo, in a 1:1 ratio for the first 12 months. The starting dose will be 1000 mg daily, and depending on tolerability, doses may be decreased. Baseline evaluations will be comprised of: blood tests; clinical evaluations; skin biopsy; eye examination; bone density test; and photography of skin lesions. Subjects will be evaluated at week 2, week 6, month 3, and then every 3 months during the first year. Upon completion of the first year, barring any safety concerns, all subjects will be administered magnesium oxide supplements for up to one additional year. Subjects will undergo the same evaluations/ procedures every 3 months. We hypothesize that the magnesium oxide will cause a reduction in calcifications in the subject's soft tissue/skin. Funding Source - FDA OOPD.
详细描述
Pseudoxanthoma elasticum (PXE) is a systemic connective tissue disorder involving elastic fiber calcification and fragmentation with major clinical manifestations occurring in the cutaneous, ocular and cardiovascular systems.
Calcification of the elastic fibers leads to cracks in Bruch's membrane, an elastic tissue-containing membrane that separates the vascular choroid from the retinal pigment epithelium. These are known as angioid streaks and may be the only sign of the disease for years. Retinal hemorrhage and loss of vision are common. Calcification of the internal elastic lamina of arteries results in gastrointestinal bleeding, sometimes fatal in nature. Accelerated heart disease is an additional complication.
Cutaneous manifestations are characterized by the presence of yellow papules in a cobblestone pattern or plaques resembling "plucked chicken-skin" in flexural regions. Redundant folds of skin may develop in more advanced cases. The most frequent sites of cutaneous involvement include the neck, axillae, inguinal region, antecubital and popliteal fossae and the periumbilical area. Skin lesions provide an easy way of grading degree of calcification of elastic tissue.
A clinical study of 80 subjects with a variety of cutaneous soft tissue mineralization disorders had the affected areas injected locally with magnesium sulfate while also receiving oral magnesium lactate for 4 to 6 months. About 75% of these subjects showed a significant decrease or complete disappearance of calcification.
More recently, a knockout mouse model for PXE has linked a reversal in calcification to a diet high in magnesium. Mice were placed on diets that were either high or low in phosphate, high or low in magnesium, or on a controlled diet. The mice placed on the high magnesium diet did not show any evidence of connective tissue mineralization, while those on the other diets did show mineralization as characterized by calcification of the connective tissue capsule surrounding the vibrissae.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female subject at least 18 years of age
- •If female, the subject is not pregnant or nursing
- •If female of child bearing potential, the subject has a negative urine pregnancy test at the first visit, and agrees to use an approved method of contraception (hormonal contraceptives [birth control pills, implants [Norplant] or injections [DepoProvera]); intrauterine device (IUD); two forms of barrier methods [condoms and diaphragm]; or abstinence (no sexual activity) throughout the entire study
- •Biopsy confirmed diagnosis of pseudoxanthoma elasticum (documenting some calcification of elastic fibers)
- •Subject has a clinical disease severity grade of at least "1" (Poorly defined, barely visible macules) at screening.
- •Normal kidney function tests
排除标准
- •Any subject who is pregnant or becomes pregnant during the study
- •Subjects with a serum creatinine greater than 1.6 mg/dL
- •Subjects with hypermagnesemia, hypokalemia, or idiopathic hypercalciuria
- •Subjects with kidney disease or renal tubular defects (eg. Fanconi's syndrome), or on dialysis
- •Subjects with hypothyroidism or hypoparathyroidism or primary hyperparathyroidism
- •Subjects with acute gout
- •Subjects with malabsorption, or osteomalacia
- •Subjects on diuretics, magnesium containing antacids, or anabolic steroids
- •Subjects with Cushing's syndrome
- •Subjects receiving lithium and those with significant psychiatric disorders that would likely interfere with participation in this study
- •Subjects taking anti-seizures medications and anti-arrhythmics medications
- •Subjects on tetracycline or metronidazole and ace inhibitors
- •Subjects taking cyclosporine or calcineurin inhibitors
研究组 & 干预措施
Magnesium oxide
Part 1: 1000 mg elemental magnesium (given as one 800 mg capsule of magnesium oxide two times daily).
Part 2: 1500 mg elemental magnesium (given as two 500 mg capsules of magnesium oxide in the morning and three 500 mg capsules of magnesium oxide in the evening).
干预措施: Magnesium Oxide (Drug)
Placebo
Part 1: 1000 mg (one 500 mg capsule two times daily) of placebo.
干预措施: Placebo (Drug)
结局指标
主要结局
Von Kossa Staining Per Unit Area of Dermis
时间窗: up to 2 years
A blinded dermatopathologist graded skin biopsies on the density of Von Kossa staining, assessed changes in the amount of calcification of elastic fibers by assessing von Kossa staining per unit area of dermis
次要结局
- VAS - Visual Acuity Score(2 years)
- Central Retinal Thickness(2 years)
- Number of Participants With a 1-point Decrease of Target Lesions(up to 2 years)
- LogMar(2 years)
研究者
Mark Lebwohl
Principal Investigator
Icahn School of Medicine at Mount Sinai