Magnesium Supplementation in Diabetic Nephropathy

Sponsor

Ain Shams University (Other)

Overall Status

Completed

CT.gov ID

NCT03824379

Collaborator

(none)

Enrollment

Location

Arms

Actual Duration (Months)

6.7

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Higher prevalence of hypomagnesaemia in diabetic patients with nephropathy was compared to those without nephropathy. Serum magnesium levels were significantly inversely correlated with serum creatinine and U-A/C ratio, and positively correlated with glomerular filtration rate (GFR).

Hence, Magnesium supplementation using magnesium salts could be a good approach to improve the cardiovascular complications, insulin resistance index, lipid profile and kidney function in diabetic nephropathy patients.

Condition or Disease	Intervention/Treatment	Phase
Diabetic Nephropathies	Dietary Supplement: Magnesium citrate Drug: Antidiabetic	Phase 2

Detailed Description

Diabetic nephropathy is a serious kidney-related complication of type 1 diabetes and type 2 diabetes. It is also called diabetic kidney disease. Up to 40 percent of people with diabetes eventually develop kidney disease. Over time, elevated blood sugar associated with uncontrolled diabetes causes high blood pressure which in turn damages the kidneys by increasing kidney filtration pressure. Complications of diabetic nephropathy include heart and blood vessel disease (cardiovascular disease), fluid retention and hyperkalemia. Magnesium (Mg) is the fourth most abundant cation in the body and the second most important intracellular cation. It plays an essential role in biological systems as co-factor for more than 300 essential enzymatic reactions such as signal transduction, energy metabolism, vascular processes and bone metabolism. Normal serum Mg concentrations ranges from 0.7 to 1.1 mmol/L (1.4-2.0 mEq/L or 1.7-2.4 mg/dL). Outcome studies in the general population have indicated potential associations between low serum Mg levels and atherosclerosis, hypertension, diabetes, and left ventricular hypertrophy, as well as both CVD mortality and all-cause mortality. Low SMg levels (1.4-1.9 mg/dL; 0.58-0.78 mM) were independently associated with all-cause death in patients with prevalent CKD. Higher prevalence of hypomagnesaemia in diabetic patients with nephropathy compared to those without nephropathy. Serum magnesium levels were significantly inversely correlated with serum creatinine and U-A/C ratio, and positively correlated with glomerular filtration rate (GFR). Magnesium deficiency promotes hydroxyapatite formation and calcification of vascular smooth muscle cells . It is closely related to insulin resistance and metabolic syndrome. A lower Mg level is directly associated with a faster deterioration of renal function in T2DM patients. Moreover, hypomagnesemia is associated with the long-term micro- and macrovascular complications of T2DM. A dysregulation of mineral metabolism, reflected by altered levels of magnesium and FGF-23, correlates with an increased urinary albumin to creatinine ratio (UACR) in type 2 diabetic patients with CKD stages 2-4. Also, a link between hypomagnesemia and atherogenic dyslipidemia alterations exists; a significantly raised total cholesterol and LDL and non-HDL in patients with CKD are observed, suggesting a link to increased cardiovascular risk in CKD patients. Increasing magnesium levels could attenuate the cardiovascular risk derived from hyperphosphatemia, hence the CKD progression. Current literature suggests that Mg may have a protective effect on the CV system. Mg supplementation improves the insulin resistance index and beta-cell function, and decreases hemoglobin A1c levels in type 2 DM patients. In animal models of vascular calcification VC, dietary supplementation with magnesium results in marked reduction in VC and mortality, improved mineral metabolism, including lowering of PTH, as well as improvement in renal function. Hence, Magnesium supplementation using magnesium salts could be a good approach to improve the cardiovascular complications, insulin resistance index, lipid profile and kidney function in diabetic nephropathy patients.

Study Design

Study Type:

Interventional

Actual Enrollment :

60 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

prospective randomized controlled open label studyprospective randomized controlled open label study

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

The Impact of Magnesium Supplementation on the Clinical Outcome of Patients of Diabetic Nephropathy

Actual Study Start Date :

Jun 1, 2019

Actual Primary Completion Date :

Mar 1, 2020

Actual Study Completion Date :

Mar 1, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Magnesium arm 30 patients will receive the standard therapy (anti-diabetic ) + magnesium supplement	Dietary Supplement: Magnesium citrate magnesium citrate equivalent 20-30 mmol elemental magnesium Drug: Antidiabetic insulin or oral hypoglycemics
Active Comparator: Control 30 patients will receive the standard therapy (anti-diabetic)	Drug: Antidiabetic insulin or oral hypoglycemics

Arm

Intervention/Treatment

Experimental: Magnesium arm

30 patients will receive the standard therapy (anti-diabetic ) + magnesium supplement

Dietary Supplement: Magnesium citrate

magnesium citrate equivalent 20-30 mmol elemental magnesium

Drug: Antidiabetic

insulin or oral hypoglycemics

Active Comparator: Control

30 patients will receive the standard therapy (anti-diabetic)

Drug: Antidiabetic

insulin or oral hypoglycemics

Outcome Measures

Primary Outcome Measures

Change of Human Serum Osteocalcin level [Change from baseline Human Serum Osteocalcin level at 12 weeks]
Evaluation of the extent of cardiovadcular events

Secondary Outcome Measures

Serum Insulin [Samples will be measured at baseline and after 12 weeks]
Evaluation of Glycemic Status
The homeostasis model assessment-estimated insulin resistance (HOMA-IR) [Assessed at baseline and after 12 weeks]
(HOMA-IR), developed by Matthews et al. will be used to assess insulin resistance. The following formula will be used in its calculation: HOMA IR = (fasting glucose mg/dl × fasting insulin μU/ml)/22.5 × 18. A normal value was considered to be <2.5
Hemoglobin A1c level [Samples will be measured at baseline and after 12 weeks]
Evaluation of Glycemic Status
Fasting and Post Prandial Blood Sugar level [Samples will be measured at baseline and after 12 weeks]
Evaluation of Glycemic Status
Serum creatinine [Samples will be measured at baseline and after 12 weeks]
Evaluation of kidney function
Blood Urea Nitrogen Concentration [Samples will be measured at baseline and after 12 weeks]
Evaluation of kidney function
eGFR using the MDRD equation [Samples will be measured at baseline and after 12 weeks]
Evaluation of kidney function. GFR (mL/min/1.73 m2) = 175 × (Scr)-1.154 × (Age)-0.203 × (0.742 if female) × (1.212 if African American)
Serum Magnesium [Samples will be measured at baseline, 6 weeks and 12 weeks]
Evaluation of SMg level
Evaluation of Lipid profile [Samples will be measured at baseline and after 12 weeks]
Serum Low-density Lipoprotein Cholesterol (LDL-C), High-density Lipoprotein Cholesterol (HDL-C), Total Cholesterol, Triglycerides
Fatigue Assessment [Assessed at baseline and after 12 weeks]
Fatigue Assessment using Fatigue Severity Scale (FSS). It is a 9-item scale which measures the severity of fatigue and its effect on a person's activities and lifestyle in a variety of disorders. > 4 points indicates no fatigue 4 points or more indicates increasing fatigue
Quality of Life (QoL) Assessment: D-39 Questionnaire [Assessed at baseline and after 12 weeks]
Quality of Life (QoL) assessment using D-39 Questionnaire

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 85 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Age ≥ 18 years.
Type I or II diabetic patientCKD stage 3 ( eGFR = 30 - 59 ml/min) or stage 4 ( eGFR 15-29 ml/min)
Proteinuria 30-300 mg/dl (microalbuminuria)
Low SMg levels (1.4-1.9 mg/dL; 0.58-0.78 mM) to normal (1.7-2.4 mg/dL; 0.7 -1.1 mmol/L; 1.4-2.0 mEq/L).
Life expectancy >12 months.
Women of child-bearing age should be using contraceptives as Hormonal contraceptive or Intra-uterine device.

Exclusion Criteria:

Kidney donor recipient.
Current treatment with Mg supplements.
Any condition impairing intestinal absorption of Mg (e.g: chronic pancreatitis, short bowel syndrome)
Active malignancy.
Pregnancy or breastfeeding.
Cardiac Arrythmias.
Allergy towards the Mg supplement.
Participation in other interventional trials.