Magnesium Supplements In The Treatment Of Pseudoxanthoma Elasticum (PXE)

February 16, 2021 updated by: Mark Lebwohl
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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

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.

Based on this information and the research linking increased magnesium levels to decreased calcification, we plan to supplement the diets of PXE patients with magnesium oxide in order to show a reduction in elastic fiber calcification in the skin and to slow the progression of the disease.

Randomized subjects will be instructed to take study drug (active or placebo) for 12 months, then all subjects will receive active study drug for the following 12 months.

When ingested through foods, magnesium has not demonstrated any adverse effects. When obtained through supplements, however, excessive magnesium intake has been known to result in diarrhea as well as other gastrointestinal effects such as nausea, and abdominal cramping. Large pharmacological doses of magnesium have been associated with more serious side effects, such as metabolic alkalosis and hypokalemia with the repeated daily ingestion of 30g of magnesium oxide. Hypermagnesemia may result with excessive magnesium supplement ingestion, however, it has rarely been reported in individuals with normal renal function.

Study data will be analyzed using the Wilcoxon Rank Sum Test to compare changes in physician global assessment of skin lesions, evaluation of target lesions and assessment of biopsies between treatment and placebo groups. Assuming a negligible placebo response, we believe power analyses can be performed on our primary measure in 40 completed subjects as proposed in this study. Analyses will be based on intent-to-treat, with the last observation carried forward. Patients who withdraw for safety, lack of efficacy, and generally those without other documentation will in the absence of the requested 'final-visit evaluation' be assigned the highest (worst) score. A finding of significance based on the intent-to-treat analysis would be supplemented with an analysis of patients completing the trial without any protocol deviations.

Study Type

Interventional

Enrollment (Actual)

44

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • New York
      • New York, New York, United States, 10029
        • Icahn School of Medicine at Mount Sinai

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: 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).
Drug: 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).

Other Names:
  • magnesium oxide supplement
Placebo Comparator: Placebo
Part 1: 1000 mg (one 500 mg capsule two times daily) of placebo.
Drug: Placebo
1000 mg (one 500 mg capsule two times daily) of placebo.
Other Names:
  • silica and/or cellulose

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Von Kossa Staining Per Unit Area of Dermis
Time Frame: 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
up to 2 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants With a 1-point Decrease of Target Lesions
Time Frame: up to 2 years
Changes in skin skin lesions observed through investigator evaluations and clinical photographs. The number of patients with a 1-point decrease of target lesions
up to 2 years
LogMar
Time Frame: 2 years
Rate of disease progression - Changes observed through ophthalmologic examinations. (+) a decrease in this score indicates improvement of the disease (-) an increase in this score indicates worsening of the disease. LogMAR: logarithm of the minimum angle of resolution. The LogMAR scale converts the geometric sequence of a traditional chart to a linear scale. It measures visual acuity loss: positive values indicate vision loss, while negative values denote normal or better visual acuity.
2 years
VAS - Visual Acuity Score
Time Frame: 2 years
Rate of disease progression observed through ophthalmologic examinations.(+) an increase in this score indicates improvement of the disease (-) a decrease in this score indicates worsening of the disease. VAS ranges from 10 to 200, with higher score indicating poorer visual acuity.
2 years
Central Retinal Thickness
Time Frame: 2 years
Rate of disease progression observed through ophthalmologic examinations. (+) a decrease in this scores indicates improvement of the disease; (-) an increase in this scores indicates improvement of the disease.
2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Mark Lebwohl

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

August 1, 2012

Primary Completion (Actual)

March 1, 2015

Study Completion (Actual)

March 1, 2015

Study Registration Dates

First Submitted

February 1, 2012

First Submitted That Met QC Criteria

February 1, 2012

First Posted (Estimate)

February 3, 2012

Study Record Updates

Last Update Posted (Actual)

March 10, 2021

Last Update Submitted That Met QC Criteria

February 16, 2021

Last Verified

February 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • GCO 09-1157
  • FD-R-0003903 (Other Grant/Funding Number: FDA OOPD)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Pseudoxanthoma Elasticum

Clinical Trials on Magnesium Oxide

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Mali

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe