The Impact of Magnesium Supplementation on Insulin Resistance and Secretion in Renal Transplant Recipients

Hypomagnesemia is common in renal transplant recipients and is mainly because of enhanced renal magnesium wasting, caused by immunosuppressive drugs (calcineurin inhibitors). Glucose metabolism disorders, including insulin resistance and decreased insulin secretion, are also prevalent post-transplantation and often precede the development of diabetes. As magnesium supplementation has been demonstrated to increase insulin sensitivity in both diabetic and non-diabetic patients, its potential therapeutic supplementation (post-transplantation) deserves further examination. The hypothesis is that magnesium supplementation in renal transplant recipients exerts a beneficial effect on insulin resistance and/or secretion.

Study Overview

• Status: Completed
• Conditions: Glucose Metabolism; Renal Transplantation
• Intervention / Treatment: Dietary supplement: magnesium supplementation

• Study Type: Interventional
• Enrollment (Actual): 70
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Belgium
  • Aalst, Belgium
    • OLV Aalst
  • Ghent, Belgium, 9000
    • University Hospital Ghent

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:

• Renal transplantation recipients
• > 18 years of age
• more than 4 months post-transplantation
• Hypomagnesemia < 1,8 milligram/deciliter on 2 consecutive blood samples (laboratory reference interval 1,7 - 2,55 milligram/deciliter) at least 1 month apart.

Exclusion Criteria:

• Pre-existing diabetes mellitus defined as the intake of anti-diabetic drugs at the time of inclusion
• Biopsy that proves acute rejection and consecutive treatment with corticosteroid boluses less than 2 months before inclusion
• Serum creatinine > 3 milligram/deciliter
• Active infection (C reactive protein > 3 milligram/deciliter)
• Severe hypomagnesemia (< 1,2 milligram/deciliter)
• Hypokalemia (< 3,5 milli-equivalent/liter)
• Severe hypocalcemia (< 6,5 milligram/deciliter)
• Intake of digoxin
• Intake of magnesium supplementation up to 2 weeks before randomization.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: hypomagnesemic + magnesium supplement; The patient group of hypomagnesesemic renal transplant recipients randomized to magnesium supplementation (number = 30). The assessments are a baseline fasting assessment of insulin resistance and an Oral Glucose Tolerance Test with derived indices of insulin secretion,which are repeated after 6 months.	Dietary supplement: magnesium supplementation; The supplementation starts with 450 mg of magnesium oxide daily, up to a maximum of 3 times 450 mg daily, while aiming at a serum magnesium level of > 1,9 mg/dl.
No Intervention: hypomagnesemic without magnesium supplement; The patient group of hypomagnesesemic renal transplantation recipients, randomized to no magnesium supplementation (number = 30). During 6 months, no magnesium supplementation is started, provided that the serum magnesium level remains > 1,2 milligram/deciliter. In case of cramps, intermittent supplementation is allowed, but will be recorded. The assessments are a baseline fasting assessment of insulin resistance and an Oral Glucose Tolerance Test with derived indices of insulin secretion,which are repeated after 6 months.
No Intervention: normomagnesemic without magnesium supplement; In the control group of normomagnesemic renal transplantation recipients (number = 10), only a baseline assessment will be performed. The assessments are a baseline fasting assessment of insulin resistance and an Oral Glucose Tolerance Test with derived indices of insulin secretion.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluation of change in insulin resistance/secretion	The primary outcome of the study is the evaluation of change in insulin resistance and insulin secretion after 6 months of supplementation (versus no supplementation). Insulin resistance is measured by 'Homeostatic Model Assessment' (HOMA) - modeling and the McAuley Index. Insulin secretion is assessed by 'Oral Glucose Tolerance test' (OGTT)- derived indices.	after 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluation of change in Hemoglobin A1c (HbA1C)	The secondary outcome is the evaluation of change in Hemoglobin A1c after 6 months of magnesium supplementation versus no supplementation.	after 6 months

Collaborators and Investigators

• Sponsor: University Hospital, Ghent
• Collaborators: Astellas Pharma Inc
• Investigators: Principal Investigator: Steven Van Laecke, MD, University Hospital, Ghent

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: January 1, 2011
• Primary Completion (Actual): December 1, 2015
• Study Completion (Actual): December 1, 2015

Study Registration Dates

• First Submitted: February 4, 2011
• First Submitted That Met QC Criteria: February 4, 2011
• First Posted (Estimate): February 7, 2011

Study Record Updates

• Last Update Posted (Estimate): January 18, 2017
• Last Update Submitted That Met QC Criteria: January 16, 2017
• Last Verified: January 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Hyperinsulinism; Insulin Resistance
• Other Study ID Numbers: 2010/416