Magnesium Supplementation in Diabetic Nephropathy

Diabetic Nephropathies Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03824379
• Other study ID #: PHCL932
• Status: Completed
• Phase: Phase 2
• Start date: June 1, 2019
• Est. completion date: March 1, 2020

Study information

• Verified date: January 2021
• Source: Ain Shams University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 60
• Est. completion date: March 1, 2020
• Est. primary completion date: March 1, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

Inclusion Criteria:

1. Age = 18 years.

2. Type I or II diabetic patientCKD stage 3 ( eGFR = 30 - 59 ml/min) or stage 4 ( eGFR 15-29 ml/min)

3. Proteinuria 30-300 mg/dl (microalbuminuria)

4. 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).

5. Life expectancy >12 months.

6. Women of child-bearing age should be using contraceptives as Hormonal contraceptive or Intra-uterine device.

Exclusion Criteria:

1. Kidney donor recipient.

2. Current treatment with Mg supplements.

3. Any condition impairing intestinal absorption of Mg (e.g: chronic pancreatitis, short bowel syndrome)

4. Active malignancy.

5. Pregnancy or breastfeeding.

6. Cardiac Arrythmias.

7. Allergy towards the Mg supplement.

8. Participation in other interventional trials.

Related Conditions & MeSH terms

• Diabetic Nephropathies
• Kidney Diseases

Intervention

Dietary Supplement:
• Magnesium citrate
magnesium citrate equivalent 20-30 mmol elemental magnesium

Drug:
• Antidiabetic
insulin or oral hypoglycemics

Locations

Country	Name	City	State
Egypt	Ain Shams University Hospitals	Cairo	Abbasseia

Sponsors (1)

Lead Sponsor	Collaborator
Ain Shams University

Country where clinical trial is conducted

Egypt, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change of Human Serum Osteocalcin level	Evaluation of the extent of cardiovadcular events	Change from baseline Human Serum Osteocalcin level at 12 weeks
Secondary	Serum Insulin	Evaluation of Glycemic Status	Samples will be measured at baseline and after 12 weeks
Secondary	The homeostasis model assessment-estimated insulin resistance (HOMA-IR)	(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	Assessed at baseline and after 12 weeks
Secondary	Hemoglobin A1c level	Evaluation of Glycemic Status	Samples will be measured at baseline and after 12 weeks
Secondary	Fasting and Post Prandial Blood Sugar level	Evaluation of Glycemic Status	Samples will be measured at baseline and after 12 weeks
Secondary	Serum creatinine	Evaluation of kidney function	Samples will be measured at baseline and after 12 weeks
Secondary	Blood Urea Nitrogen Concentration	Evaluation of kidney function	Samples will be measured at baseline and after 12 weeks
Secondary	eGFR using the MDRD equation	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)	Samples will be measured at baseline and after 12 weeks
Secondary	Serum Magnesium	Evaluation of SMg level	Samples will be measured at baseline, 6 weeks and 12 weeks
Secondary	Evaluation of Lipid profile	Serum Low-density Lipoprotein Cholesterol (LDL-C), High-density Lipoprotein Cholesterol (HDL-C), Total Cholesterol, Triglycerides	Samples will be measured at baseline and after 12 weeks
Secondary	Fatigue Assessment	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	Assessed at baseline and after 12 weeks
Secondary	Quality of Life (QoL) Assessment: D-39 Questionnaire	Quality of Life (QoL) assessment using D-39 Questionnaire	Assessed at baseline and after 12 weeks