Magnesium Supplements In The Treatment Of Pseudoxanthoma Elasticum (PXE)

NCT01525875 | Completed Phase 2 Results DMC

• 2 other identifiers: GCO 09-1157FD-R-0003903
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 1

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.

Conditions

Pseudoxanthoma Elasticum

Keywords

pseudoxanthoma elasticum; calcification

Outcome Measures

Primary Outcomes (1)

• Von Kossa Staining Per Unit Area of Dermis

  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 Outcomes (4)

• Number of Participants With a 1-point Decrease of Target Lesions

  up to 2 years

• LogMar

  2 years

• VAS - Visual Acuity Score

  2 years

• Central Retinal Thickness

  2 years

Study Arms (2)

Magnesium oxide

ACTIVE COMPARATOR

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

Placebo

PLACEBO COMPARATOR

Part 1: 1000 mg (one 500 mg capsule two times daily) of placebo.

Drug: Placebo

Interventions

Magnesium Oxide DRUG

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).

Also known as: magnesium oxide supplement

Magnesium oxide

Placebo DRUG

1000 mg (one 500 mg capsule two times daily) of placebo.

Also known as: silica and/or cellulose

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Mark Lebwohl: lead

Study Sites (1)

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

Location

Related Publications (17)

• Lebwohl M, Neldner K, Pope FM, De Paepe A, Christiano AM, Boyd CD, Uitto J, McKusick VA. Classification of pseudoxanthoma elasticum: report of a consensus conference. J Am Acad Dermatol. 1994 Jan;30(1):103-7. doi: 10.1016/s0190-9622(08)81894-4. No abstract available.

  PMID: 8277008 BACKGROUND

• Neldner KH. Pseudoxanthoma elasticum. Clin Dermatol. 1988 Jan-Mar;6(1):1-159. doi: 10.1016/0738-081x(88)90003-x. No abstract available.

  PMID: 3359381 BACKGROUND

• Clarkson JG, Altman RD. Angioid streaks. Surv Ophthalmol. 1982 Mar-Apr;26(5):235-46. doi: 10.1016/0039-6257(82)90158-8.

  PMID: 7046115 BACKGROUND

• Renie WA, Pyeritz RE, Combs J, Fine SL. Pseudoxanthoma elasticum: high calcium intake in early life correlates with severity. Am J Med Genet. 1984 Oct;19(2):235-44. doi: 10.1002/ajmg.1320190205.

  PMID: 6507474 BACKGROUND

• Martinez-Hernandez A, Huffer WE, Neldner K, Gordon S, Reeve EB. Resolution and repair of elastic tissue calcification in pseudoxanthoma elasticum. Arch Pathol Lab Med. 1978 Jun;102(6):303-5.

  PMID: 580723 BACKGROUND

• Sapadin AN, Lebwohl MG, Teich SA, Phelps RG, DiCostanzo D, Cohen SR. Periumbilical pseudoxanthoma elasticum associated with chronic renal failure and angioid streaks--apparent regression with hemodialysis. J Am Acad Dermatol. 1998 Aug;39(2 Pt 2):338-44. doi: 10.1016/s0190-9622(98)70385-8.

  PMID: 9703148 BACKGROUND

• Sherer DW, Singer G, Uribarri J, Phelps RG, Sapadin AN, Freund KB, Yanuzzi L, Fuchs W, Lebwohl M. Oral phosphate binders in the treatment of pseudoxanthoma elasticum. J Am Acad Dermatol. 2005 Oct;53(4):610-5. doi: 10.1016/j.jaad.2004.11.066.

  PMID: 16198780 BACKGROUND

• Blum R, Phelps R, Fuchs W, Lebwohl M. Oral Phosphate Binders in the Treatment of Pseudoxanthoma Elasticum. 64th Annual Meeting American Academy of Dermatology March 3-7, 2006, San Francisco, CA. Manuscript in press J Amer Acad Dermatol 2011

  BACKGROUND

• Steidl L, Ditmar R. Treatment of soft tissue calcifications with magnesium. Acta Univ Palacki Olomuc Fac Med. 1991;130:273-87.

  PMID: 1838878 BACKGROUND

• LaRusso J, Li Q, Jiang Q, Uitto J. Elevated dietary magnesium prevents connective tissue mineralization in a mouse model of pseudoxanthoma elasticum (Abcc6(-/-)). J Invest Dermatol. 2009 Jun;129(6):1388-94. doi: 10.1038/jid.2008.391. Epub 2009 Jan 1.

  PMID: 19122649 BACKGROUND

• Iseri LT, French JH. Magnesium: nature's physiologic calcium blocker. Am Heart J. 1984 Jul;108(1):188-93. doi: 10.1016/0002-8703(84)90572-6. No abstract available.

  PMID: 6375330 BACKGROUND

• Joffres MR, Reed DM, Yano K. Relationship of magnesium intake and other dietary factors to blood pressure: the Honolulu heart study. Am J Clin Nutr. 1987 Feb;45(2):469-75. doi: 10.1093/ajcn/45.2.469.

  PMID: 3812346 BACKGROUND

• Paolisso G, Passariello N, Pizza G, Marrazzo G, Giunta R, Sgambato S, Varricchio M, D'Onofrio F. Dietary magnesium supplements improve B-cell response to glucose and arginine in elderly non-insulin dependent diabetic subjects. Acta Endocrinol (Copenh). 1989 Jul;121(1):16-20. doi: 10.1530/acta.0.1210016.

  PMID: 2662695 BACKGROUND

• Rude RK, Singer FR. Magnesium deficiency and excess. Annu Rev Med. 1981;32:245-59. doi: 10.1146/annurev.me.32.020181.001333. No abstract available.

  PMID: 7013665 BACKGROUND

• Dietary Reference Intakes for Calcium, Magnesium, Vitamin D and Flouride. IOM Institute of Medicine. 1997 Washington, DC: National Academy Press.

  BACKGROUND

• Bashir Y, Sneddon JF, Staunton HA, Haywood GA, Simpson IA, McKenna WJ, Camm AJ. Effects of long-term oral magnesium chloride replacement in congestive heart failure secondary to coronary artery disease. Am J Cardiol. 1993 Nov 15;72(15):1156-62. doi: 10.1016/0002-9149(93)90986-m.

  PMID: 8237806 BACKGROUND

• Urakabe S, Nakata K, Ando A, Orita Y, Abe H. Hypokalemia and metabolic alkalosis resulting from overuse of magnesium oxide. Jpn Circ J. 1975 Oct;39(10):1135-7. doi: 10.1253/jcj.39.1135.

  PMID: 1195509 BACKGROUND

MeSH Terms

Conditions

Pseudoxanthoma Elasticum; Calcinosis

Interventions

Magnesium Oxide

Condition Hierarchy (Ancestors)

Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Hemorrhagic Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Skin Abnormalities; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Skin Diseases, Genetic; Genetic Diseases, Inborn; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Skin Diseases; Calcium Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Magnesium Compounds; Inorganic Chemicals; Oxides; Oxygen Compounds

Limitations and Caveats

Small study of a rare disease with tremendous patient variation.

Results Point of Contact

• Title: Dr. Mark Lebwohl
• Organization: Icahn School of Medicine at Mount Sinai

mark.lebwohl@mountsinai.org

212-241-9728

Study Officials

• Mark Lebwohl, MD

  Icahn School of Medicine at Mount Sinai

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: February 1, 2012
• First Posted: February 3, 2012
• Study Start: August 1, 2012
• Primary Completion: March 1, 2015
• Study Completion: March 1, 2015
• Last Updated: March 10, 2021
• Results First Posted: April 25, 2019

Record last verified: 2021-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)