Clinical Trial: Magnesium Supplements In The Treatment Of Pseudoxanthoma Elasticum (PXE)

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Magnesium Supplements In The Treatment Of Pseudoxanthoma Elasticum (PXE)

Brief Summary: 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.

Detailed Summary:

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 controll
Sponsor: Mark Lebwohl

Current Primary Outcome: Reversal of elastic fiber calcification [ Time Frame: Baseline, Month 12, and Month 24 ]

A blinded dermatopathologist will grade skin biopsies on the density of Von Kossa staining. We will assess changes in the amount of calcification of elastic fibers by assessing von Kossa staining per unit area of dermis


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Reversal of clinical skin lesions [ Time Frame: Screening, Months 6, 12, 18 and 24 ]
    Changes in skin skin lesions observed through investigator evaluations and clinical photographs
  • Rate of disease progression [ Time Frame: Baseline, Month 12 and Month 24 ]
    Changes observed through ophthalmologic examinations
  • Rate of disease progression [ Time Frame: Month 12 ]
    Observed through ophthalmologic examinations
  • Rate of disease progression [ Time Frame: Month 24 ]
    Observed through ophthalmologic examinations


Original Secondary Outcome: Same as current

Information By: Icahn School of Medicine at Mount Sinai

Dates:
Date Received: February 1, 2012
Date Started: August 2012
Date Completion:
Last Updated: January 19, 2016
Last Verified: January 2016