Effect of Oral Magnesium on Vascular Calcification in Chronic Kidney Disease (MagiCal-CKD)

The Effect of Oral Magnesium Supplementation on Vascular Calcification in Chronic Kidney Disease - A Randomized Clinical Trial

Randomized placebo-controlled double-blinded interventional trial to investigate the effect of oral magnesium supplementation on vascular calcification in subjects with chronic kidney disease. We hypothesize that oral magnesium supplementation will reduce vascular calcification in subjects with chronic kidney disease while not decreasing bone mineral density.

Study Overview

• Status: Completed
• Conditions: Chronic Kidney Disease; Vascular Calcification; Uremic Osteodystrophy
• Intervention / Treatment: Dietary supplement: Placebo; Dietary supplement: Mablet 360 mg

Detailed Description

Chronic kidney disease (CKD) is associated with increase cardiovascular morbidity and mortality independent of traditional cardiovascular risk factors due to increased vascular calcification. Epidemiological and experimental data suggest that hypermagnesemia and magnesium supplementation reduce vascular calcification in CKD by increasing calcium/phosphate solubility in serum, by inhibiting calcium influx into vascular smooth muscle cells (VSMC), by inhibiting intracellular pro-calcification enzymes in VSMC and by increasing activity of intracellular anti-calcification enzymes in VSMC. However, there have been concerns that any anti-calcification effect of magnesium might also reduce bone mineral density, in which case there might be an increased risk of bone fractures associated with magnesium supplementation in CKD. We wish to conduct a randomized placebo-controlled double-blinded interventional trial to examine whether oral magnesium supplementation will reduce vascular calcification in subjects with CKD while not decreasing bone mineral density.

• Study Type: Interventional
• Enrollment (Actual): 148
• Phase: Phase 2

Contacts and Locations

Study Locations

• Denmark
  • Herlev, Denmark, 2730
    • Herlev Hospital
  • Hillerød, Denmark, 3400
    • Nordsjællands Hospital
• Norway
  • Lørenskog, Norway, 1478
    • Akershus universitetssykehus

Participation Criteria

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:

• Estimated glomerular filtration rate between 45 and 15 mL/min for > 3 months (i.e. CKD stage 3b-4).
• Serum total magnesium < 0,82 mmol/L and serum phosphate > 1,15 mmol/L on average of previous measurements.

or Serum total magnesium < 0,92 mmol/L and serum phosphate > 1,30 mmol/L on average of previous measurements.

• Life expectancy > 1 year.
• Expected time until initiation of dialysis or transplantation > 1 year.
• Women of childbearing age must be actively using contraceptive therapy (p-pills, estrogen depots or intrauterine device) as well as have a negative pregnancy test.
• Written informed consent.

Exclusion Criteria:

• Current hemodialysis or peritoneal dialysis treatment.
• Kidney donor recipient.
• Previous coronary artery bypass graft (CABG).
• Parathyroid hormone > 600 ρmol/L.
• Previous parathyroidectomy.
• Current treatment with magnesium containing medication or supplements.
• Any condition impairing magnesium absorption from the gastrointestinal tract (e.g. short bowel syndrome, chronic pancreatitis).
• Active malignancy (basal or squamous cell skin carcinoma, localized prostate cancer and cancer with no signs of reoccurrence after 5 years are exempt from this).
• Other diseases or conditions, which, in the opinion of the site investigator, would prevent participation in or completion of trial.
• Pregnancy or breastfeeding.
• Allergy towards contents of interventional medication.
• Participation in other interventional trials.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Magnesium; Oral Magnesium Hydroxide (Mablet 360 mg) twice daily for 12 months.	Dietary supplement: Mablet 360 mg
PLACEBO_COMPARATOR: Placebo; Matching placebo tablets twice daily for 12 months.	Dietary supplement: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Coronary Artery Calcification (CAC) score	Agatston score assessed by CT scan.	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Bone Mineral Density (BMD)	BMD assessed by quantitative CT.	12 months
Pulse Wave Velocity		12 months.
Serum Calcification Propensity	Serum calcification propensity assessed by T50 analysis.	12 months.

Collaborators and Investigators

• Sponsor: Nordsjaellands Hospital
• Collaborators: Herlev Hospital
• Investigators: Principal Investigator: Iain O Bressendorff, MD, PhD, Nordsjaellands Hospital

Publications and helpful links

General Publications

• Bressendorff I, Hansen D, Schou M, Kragelund C, Brandi L. The effect of magnesium supplementation on vascular calcification in chronic kidney disease-a randomised clinical trial (MAGiCAL-CKD): essential study design and rationale. BMJ Open. 2017 Jun 23;7(6):e016795. doi: 10.1136/bmjopen-2017-016795.

Study record dates

Study Major Dates

• Study Start: November 1, 2015
• Primary Completion (ACTUAL): November 1, 2020
• Study Completion (ACTUAL): July 1, 2021

Study Registration Dates

• First Submitted: September 3, 2015
• First Submitted That Met QC Criteria: September 4, 2015
• First Posted (ESTIMATE): September 7, 2015

Study Record Updates

• Last Update Posted (ACTUAL): September 6, 2022
• Last Update Submitted That Met QC Criteria: September 1, 2022
• Last Verified: June 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Urologic Diseases; Renal Insufficiency; Calcium Metabolism Disorders; Kidney Diseases; Renal Insufficiency, Chronic; Calcinosis; Vascular Calcification
• Other Study ID Numbers: MagiCal-CKD