Trial Outcomes & Findings for Magnesium Supplements In The Treatment Of Pseudoxanthoma Elasticum (PXE) (NCT NCT01525875)

Last Updated: 2021-03-10

Results Overview

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

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

44 participants

Primary outcome timeframe

up to 2 years

Results posted on

2021-03-10

Participant Flow

Participant milestones

Participant milestones
Measure	Magnesium Oxide Magnesium oxide capsules 800mg twice daily (total of 1000mg of elemental magnesium) for year 1. Upon completion of the first year, barring any safety concerns, all subjects were administered 2500 mg magnesium oxide (total of 1500 mg elemental magnesium) daily for up to one additional year. Subjects received 600 mg elemental magnesium oxide in the morning (taken as two 500 mg magnesium oxide capsules, each containing 300 mg elemental magnesium) and 900 mg elemental magnesium oxide in the evening (taken as three 500 mg magnesium oxide capsules, each containing 300 mg elemental magnesium).	Placebo Placebo year 1. Upon completion of the first year, barring any safety concerns, all subjects were administered 2500 mg magnesium oxide (total of 1500 mg elemental magnesium) daily for up to one additional year. Subjects received 600 mg elemental magnesium oxide in the morning (taken as two 500 mg magnesium oxide capsules, each containing 300 mg elemental magnesium) and 900 mg elemental magnesium oxide in the evening (taken as three 500 mg magnesium oxide capsules, each containing 300 mg elemental magnesium).
Placebo-controlled Period STARTED	22	22
Placebo-controlled Period COMPLETED	21	20
Placebo-controlled Period NOT COMPLETED	1	2
Open-label Period STARTED	21	20
Open-label Period COMPLETED	21	18
Open-label Period NOT COMPLETED	0	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Magnesium Oxide Magnesium oxide capsules 800mg twice daily (total of 1000mg of elemental magnesium) for year 1. Upon completion of the first year, barring any safety concerns, all subjects were administered 2500 mg magnesium oxide (total of 1500 mg elemental magnesium) daily for up to one additional year. Subjects received 600 mg elemental magnesium oxide in the morning (taken as two 500 mg magnesium oxide capsules, each containing 300 mg elemental magnesium) and 900 mg elemental magnesium oxide in the evening (taken as three 500 mg magnesium oxide capsules, each containing 300 mg elemental magnesium).	Placebo Placebo year 1. Upon completion of the first year, barring any safety concerns, all subjects were administered 2500 mg magnesium oxide (total of 1500 mg elemental magnesium) daily for up to one additional year. Subjects received 600 mg elemental magnesium oxide in the morning (taken as two 500 mg magnesium oxide capsules, each containing 300 mg elemental magnesium) and 900 mg elemental magnesium oxide in the evening (taken as three 500 mg magnesium oxide capsules, each containing 300 mg elemental magnesium).
Placebo-controlled Period Withdrawal by Subject	1	2
Open-label Period Lost to Follow-up	0	2

Baseline Characteristics

Magnesium Supplements In The Treatment Of Pseudoxanthoma Elasticum (PXE)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Magnesium Oxide n=22 Participants Magnesium oxide capsules 800mg twice daily (total of 1000mg of elemental magnesium) for year 1. Upon completion of the first year, barring any safety concerns, all subjects were administered 2500 mg magnesium oxide (total of 1500 mg elemental magnesium) daily for up to one additional year. Subjects received 600 mg elemental magnesium oxide in the morning (taken as two 500 mg magnesium oxide capsules, each containing 300 mg elemental magnesium) and 900 mg elemental magnesium oxide in the evening (taken as three 500 mg magnesium oxide capsules, each containing 300 mg elemental magnesium).	Placebo n=22 Participants Placebo year 1. Upon completion of the first year, barring any safety concerns, all subjects were administered 2500 mg magnesium oxide (total of 1500 mg elemental magnesium) daily for up to one additional year. Subjects received 600 mg elemental magnesium oxide in the morning (taken as two 500 mg magnesium oxide capsules, each containing 300 mg elemental magnesium) and 900 mg elemental magnesium oxide in the evening (taken as three 500 mg magnesium oxide capsules, each containing 300 mg elemental magnesium).	Total n=44 Participants Total of all reporting groups
Age, Continuous	50.409 years STANDARD_DEVIATION 12.764 • n=5 Participants	49.364 years STANDARD_DEVIATION 12.481 • n=7 Participants	49.9 years STANDARD_DEVIATION 12.5 • n=5 Participants
Sex: Female, Male Female	14 Participants n=5 Participants	18 Participants n=7 Participants	32 Participants n=5 Participants
Sex: Female, Male Male	8 Participants n=5 Participants	4 Participants n=7 Participants	12 Participants n=5 Participants
Bone Mineral Density (BMD) AP Spine	3 Participants n=5 Participants	4 Participants n=7 Participants	7 Participants n=5 Participants
Bone Mineral Density (BMD) Forearm	4 Participants n=5 Participants	4 Participants n=7 Participants	8 Participants n=5 Participants
Bone Mineral Density (BMD) Hip	1 Participants n=5 Participants	5 Participants n=7 Participants	6 Participants n=5 Participants
Peau D'Orange right eye 3 - Mostly macules with <5 papules	0 Participants n=5 Participants	3 Participants n=7 Participants	3 Participants n=5 Participants
Peau D'Orange right eye 4 - >= 5 papules	22 Participants n=5 Participants	19 Participants n=7 Participants	41 Participants n=5 Participants
Peau D'Orange left eye 3 - Mostly macules with <5 papules	0 Participants n=5 Participants	3 Participants n=7 Participants	3 Participants n=5 Participants
Subretinal fluid right eye N	20 Participants n=5 Participants	21 Participants n=7 Participants	41 Participants n=5 Participants
Subretinal fluid right eye Y	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Subretinal fluid left eye N	20 Participants n=5 Participants	20 Participants n=7 Participants	40 Participants n=5 Participants
Subretinal fluid left eye Y	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants
Peau D'Orange left eye 4 - >= 5 papules	22 Participants n=5 Participants	19 Participants n=7 Participants	41 Participants n=5 Participants
Angioid Streaks right eye 2 - cardiovascular	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Angioid Streaks right eye 3 - Paget's	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Angioid Streaks right eye 4 - secondary	21 Participants n=5 Participants	20 Participants n=7 Participants	41 Participants n=5 Participants
Angioid Streaks left eye 2	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Angioid Streaks left eye 3	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Angioid Streaks left eye 4	21 Participants n=5 Participants	20 Participants n=7 Participants	41 Participants n=5 Participants

PRIMARY outcome

Timeframe: up to 2 years

Population: Estimate: Estimated change from baseline and its standard error (SEM). After 1 year=M12-Baseline, After 2 year=M24-Baseline; during 2nd year =M24-M12.

Outcome measures

Outcome measures
Measure	Magnesium Oxide n=22 Participants Magnesium oxide capsules 800mg twice daily (total of 1000mg of elemental magnesium) for year 1. Upon completion of the first year, barring any safety concerns, all subjects were administered 2500 mg magnesium oxide (total of 1500 mg elemental magnesium) daily for up to one additional year. Subjects received 600 mg elemental magnesium oxide in the morning (taken as two 500 mg magnesium oxide capsules, each containing 300 mg elemental magnesium) and 900 mg elemental magnesium oxide in the evening (taken as three 500 mg magnesium oxide capsules, each containing 300 mg elemental magnesium).	Placebo n=22 Participants Placebo year 1. Upon completion of the first year, barring any safety concerns, all subjects were administered 2500 mg magnesium oxide (total of 1500 mg elemental magnesium) daily for up to one additional year. Subjects received 600 mg elemental magnesium oxide in the morning (taken as two 500 mg magnesium oxide capsules, each containing 300 mg elemental magnesium) and 900 mg elemental magnesium oxide in the evening (taken as three 500 mg magnesium oxide capsules, each containing 300 mg elemental magnesium).
Von Kossa Staining Per Unit Area of Dermis After 1 year	-0.0033 microns Standard Error 0.0062	0.0010 microns Standard Error 0.0065
Von Kossa Staining Per Unit Area of Dermis during 2nd year	0.0087 microns Standard Error 0.0062	0.0123 microns Standard Error 0.0070
Von Kossa Staining Per Unit Area of Dermis after 2 years	0.0054 microns Standard Error 0.0062	0.0132 microns Standard Error 0.0069

SECONDARY outcome

Timeframe: 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

Outcome measures

Outcome measures
Measure	Magnesium Oxide n=22 Participants Magnesium oxide capsules 800mg twice daily (total of 1000mg of elemental magnesium) for year 1. Upon completion of the first year, barring any safety concerns, all subjects were administered 2500 mg magnesium oxide (total of 1500 mg elemental magnesium) daily for up to one additional year. Subjects received 600 mg elemental magnesium oxide in the morning (taken as two 500 mg magnesium oxide capsules, each containing 300 mg elemental magnesium) and 900 mg elemental magnesium oxide in the evening (taken as three 500 mg magnesium oxide capsules, each containing 300 mg elemental magnesium).	Placebo n=22 Participants Placebo year 1. Upon completion of the first year, barring any safety concerns, all subjects were administered 2500 mg magnesium oxide (total of 1500 mg elemental magnesium) daily for up to one additional year. Subjects received 600 mg elemental magnesium oxide in the morning (taken as two 500 mg magnesium oxide capsules, each containing 300 mg elemental magnesium) and 900 mg elemental magnesium oxide in the evening (taken as three 500 mg magnesium oxide capsules, each containing 300 mg elemental magnesium).
Number of Participants With a 1-point Decrease of Target Lesions After 1 year	2 Participants	1 Participants
Number of Participants With a 1-point Decrease of Target Lesions during 2nd year	8 Participants	6 Participants
Number of Participants With a 1-point Decrease of Target Lesions After 2 years	9 Participants	7 Participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Magnesium Oxide n=22 Participants Magnesium oxide capsules 800mg twice daily (total of 1000mg of elemental magnesium) for year 1. Upon completion of the first year, barring any safety concerns, all subjects were administered 2500 mg magnesium oxide (total of 1500 mg elemental magnesium) daily for up to one additional year. Subjects received 600 mg elemental magnesium oxide in the morning (taken as two 500 mg magnesium oxide capsules, each containing 300 mg elemental magnesium) and 900 mg elemental magnesium oxide in the evening (taken as three 500 mg magnesium oxide capsules, each containing 300 mg elemental magnesium).	Placebo n=22 Participants Placebo year 1. Upon completion of the first year, barring any safety concerns, all subjects were administered 2500 mg magnesium oxide (total of 1500 mg elemental magnesium) daily for up to one additional year. Subjects received 600 mg elemental magnesium oxide in the morning (taken as two 500 mg magnesium oxide capsules, each containing 300 mg elemental magnesium) and 900 mg elemental magnesium oxide in the evening (taken as three 500 mg magnesium oxide capsules, each containing 300 mg elemental magnesium).
LogMar After 1 year	-0.049 LogMar Standard Error 0.036	-0.063 LogMar Standard Error 0.036
LogMar during 2nd year	0.027 LogMar Standard Error 0.041	0.015 LogMar Standard Error 0.042
LogMar After 2 years	-0.022 LogMar Standard Error 0.049	-0.047 LogMar Standard Error 0.050

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Magnesium Oxide n=22 Participants Magnesium oxide capsules 800mg twice daily (total of 1000mg of elemental magnesium) for year 1. Upon completion of the first year, barring any safety concerns, all subjects were administered 2500 mg magnesium oxide (total of 1500 mg elemental magnesium) daily for up to one additional year. Subjects received 600 mg elemental magnesium oxide in the morning (taken as two 500 mg magnesium oxide capsules, each containing 300 mg elemental magnesium) and 900 mg elemental magnesium oxide in the evening (taken as three 500 mg magnesium oxide capsules, each containing 300 mg elemental magnesium).	Placebo n=22 Participants Placebo year 1. Upon completion of the first year, barring any safety concerns, all subjects were administered 2500 mg magnesium oxide (total of 1500 mg elemental magnesium) daily for up to one additional year. Subjects received 600 mg elemental magnesium oxide in the morning (taken as two 500 mg magnesium oxide capsules, each containing 300 mg elemental magnesium) and 900 mg elemental magnesium oxide in the evening (taken as three 500 mg magnesium oxide capsules, each containing 300 mg elemental magnesium).
VAS - Visual Acuity Score After 1 year	-1.124 units on a scale Standard Error 1.141	-0.602 units on a scale Standard Error 1.140
VAS - Visual Acuity Score during 2nd year	0.795 units on a scale Standard Error 0.927	-0.729 units on a scale Standard Error 0.986
VAS - Visual Acuity Score After 2 years	-0.329 units on a scale Standard Error 1.384	-1.332 units on a scale Standard Error 1.423

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Magnesium Oxide n=22 Participants Magnesium oxide capsules 800mg twice daily (total of 1000mg of elemental magnesium) for year 1. Upon completion of the first year, barring any safety concerns, all subjects were administered 2500 mg magnesium oxide (total of 1500 mg elemental magnesium) daily for up to one additional year. Subjects received 600 mg elemental magnesium oxide in the morning (taken as two 500 mg magnesium oxide capsules, each containing 300 mg elemental magnesium) and 900 mg elemental magnesium oxide in the evening (taken as three 500 mg magnesium oxide capsules, each containing 300 mg elemental magnesium).	Placebo n=22 Participants Placebo year 1. Upon completion of the first year, barring any safety concerns, all subjects were administered 2500 mg magnesium oxide (total of 1500 mg elemental magnesium) daily for up to one additional year. Subjects received 600 mg elemental magnesium oxide in the morning (taken as two 500 mg magnesium oxide capsules, each containing 300 mg elemental magnesium) and 900 mg elemental magnesium oxide in the evening (taken as three 500 mg magnesium oxide capsules, each containing 300 mg elemental magnesium).
Central Retinal Thickness After 1 year	2.965 µm Standard Error 0.373	-3.552 µm Standard Error 3.429
Central Retinal Thickness during 2nd year	-4.203 µm Standard Error 3.877	-6.796 µm Standard Error 4.123
Central Retinal Thickness After 2 years	-1.238 µm Standard Error 3.913	-10.348 µm Standard Error 4.143

Adverse Events

Magnesium Oxide

Serious events: 0 serious events

Other events: 11 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 11 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Magnesium Oxide n=22 participants at risk Magnesium oxide capsules 800mg twice daily (total of 1000mg of elemental magnesium) for year 1. Upon completion of the first year, barring any safety concerns, all subjects were administered 2500 mg magnesium oxide (total of 1500 mg elemental magnesium) daily for up to one additional year. Subjects received 600 mg elemental magnesium oxide in the morning (taken as two 500 mg magnesium oxide capsules, each containing 300 mg elemental magnesium) and 900 mg elemental magnesium oxide in the evening (taken as three 500 mg magnesium oxide capsules, each containing 300 mg elemental magnesium).	Placebo n=22 participants at risk Placebo year 1. Upon completion of the first year, barring any safety concerns, all subjects were administered 2500 mg magnesium oxide (total of 1500 mg elemental magnesium) daily for up to one additional year. Subjects received 600 mg elemental magnesium oxide in the morning (taken as two 500 mg magnesium oxide capsules, each containing 300 mg elemental magnesium) and 900 mg elemental magnesium oxide in the evening (taken as three 500 mg magnesium oxide capsules, each containing 300 mg elemental magnesium).
Gastrointestinal disorders Diarrhea	45.5% 10/22 • Number of events 14 • 2 years	40.9% 9/22 • Number of events 9 • 2 years
Gastrointestinal disorders Loose Stool	4.5% 1/22 • Number of events 2 • 2 years	9.1% 2/22 • Number of events 2 • 2 years
Gastrointestinal disorders Abdominal Cramps	4.5% 1/22 • Number of events 2 • 2 years	0.00% 0/22 • 2 years
Gastrointestinal disorders Nausea	0.00% 0/22 • 2 years	9.1% 2/22 • Number of events 2 • 2 years
Gastrointestinal disorders Flatulance	0.00% 0/22 • 2 years	9.1% 2/22 • Number of events 2 • 2 years
Gastrointestinal disorders Bloating	4.5% 1/22 • Number of events 1 • 2 years	4.5% 1/22 • Number of events 1 • 2 years
Gastrointestinal disorders Increased bowel movements	0.00% 0/22 • 2 years	9.1% 2/22 • Number of events 2 • 2 years
Gastrointestinal disorders Loss of Appetite	4.5% 1/22 • Number of events 1 • 2 years	0.00% 0/22 • 2 years
Gastrointestinal disorders Gastroenteritis	0.00% 0/22 • 2 years	13.6% 3/22 • Number of events 3 • 2 years
Infections and infestations Upper Respiratory Infection	0.00% 0/22 • 2 years	9.1% 2/22 • Number of events 2 • 2 years
Infections and infestations Infections	4.5% 1/22 • Number of events 1 • 2 years	22.7% 5/22 • Number of events 8 • 2 years

Additional Information

Dr. Mark Lebwohl

Icahn School of Medicine at Mount Sinai

Phone: 212-241-9728

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place