Clinical trial NCT03824379: Magnesium Supplementation in Diabetic Nephropathy
Official title: The Impact of Magnesium Supplementation on the Clinical Outcome of Patients of Diabetic Nephropathy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Diabetic Nephropathies
Keywords: magnesium
diabetic nephropathy
osteocalcin
Lead sponsor: Ain Shams University
Sponsor class: OTHER
First posted: 2019-01-31
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: prospective randomized controlled open label study
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Change of Human Serum Osteocalcin level
timeFrame: Change from baseline Human Serum Osteocalcin level at 12 weeks
Secondary outcomes:
measure: Serum Insulin
timeFrame: Samples will be measured at baseline and after 12 weeks
measure: The homeostasis model assessment-estimated insulin resistance (HOMA-IR)
timeFrame: Assessed at baseline and after 12 weeks
measure: Hemoglobin A1c level
timeFrame: Samples will be measured at baseline and after 12 weeks
measure: Fasting and Post Prandial Blood Sugar level
timeFrame: Samples will be measured at baseline and after 12 weeks
measure: Serum creatinine
timeFrame: Samples will be measured at baseline and after 12 weeks
measure: Blood Urea Nitrogen Concentration
timeFrame: Samples will be measured at baseline and after 12 weeks
measure: eGFR using the MDRD equation
timeFrame: Samples will be measured at baseline and after 12 weeks
measure: Serum Magnesium
timeFrame: Samples will be measured at baseline, 6 weeks and 12 weeks
measure: Evaluation of Lipid profile
timeFrame: Samples will be measured at baseline and after 12 weeks
measure: Fatigue Assessment
timeFrame: Assessed at baseline and after 12 weeks
measure: Quality of Life (QoL) Assessment: D-39 Questionnaire
timeFrame: Assessed at baseline and after 12 weeks
Other outcomes:
Locations:
city: Cairo
country: Egypt
facility: Ain Shams University Hospitals
state: Abbasseia
Study officials:
affiliation: Faculty of Pharmacy - Ain Shams University
name: Nihal Halawa
role: PRINCIPAL_INVESTIGATOR
References: