## Protocol Section
### Identification Module
**NCT ID:** NCT03824379

**Brief Title:** Magnesium Supplementation in Diabetic Nephropathy

**Official Title:** The Impact of Magnesium Supplementation on the Clinical Outcome of Patients of Diabetic Nephropathy

#### Organization Study ID Info
**ID:** PHCL932
#### Organization
**Class:** OTHER
**Full Name:** Ain Shams University
### Status Module
#### Completion Date
**Date:** 2020-03-01

**Type:** ACTUAL

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2021-01-12

**Type:** ACTUAL

**Last Update Submit Date:** 2021-01-11

**Overall Status:** COMPLETED

#### Primary Completion Date
**Date:** 2020-03-01

**Type:** ACTUAL

#### Start Date
**Date:** 2019-06-01

**Type:** ACTUAL

**Status Verified Date:** 2021-01

#### Study First Post Date
**Date:** 2019-01-31
**Type:** ACTUAL
**Study First Submit Date:** 2019-01-26
**Study First Submit QC Date:** 2019-01-29
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** OTHER

**Name:** Ain Shams University

#### Responsible Party

**Investigator Affiliation:** Ain Shams University

**Investigator Full Name:** Nihal Mohamed Halawa

**Investigator Title:** clinical Pharmacist

**Type:** PRINCIPAL_INVESTIGATOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** False

**Oversight Has DMC:** False

### Description Module

**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.

### Conditions Module

**Conditions:**

- Diabetic Nephropathies

**Keywords:**

- magnesium

- diabetic nephropathy

- osteocalcin

### Design Module

#### Design Info

**Allocation:** RANDOMIZED

**Intervention Model:** PARALLEL

**Intervention Model Description:** prospective randomized controlled open label study

##### Masking Info

**Masking:** NONE

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 60

**Type:** ACTUAL

**Phases:**

- PHASE2

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

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

**Intervention Names:**

- Dietary Supplement: Magnesium citrate

- Drug: Antidiabetic

**Label:** Magnesium arm

**Type:** EXPERIMENTAL

#### Arm Group 2

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

**Intervention Names:**

- Drug: Antidiabetic

**Label:** Control

**Type:** ACTIVE_COMPARATOR

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Magnesium arm

**Description:** magnesium citrate equivalent 20-30 mmol elemental magnesium

**Name:** Magnesium citrate

**Type:** DIETARY_SUPPLEMENT

#### Intervention 2

**Arm Group Labels:**

- Control

- Magnesium arm

**Description:** insulin or oral hypoglycemics

**Name:** Antidiabetic

**Type:** DRUG

### Outcomes Module

#### Primary Outcomes

**Description:** Evaluation of the extent of cardiovadcular events

**Measure:** Change of Human Serum Osteocalcin level

**Time Frame:** Change from baseline Human Serum Osteocalcin level at 12 weeks

#### Secondary Outcomes

**Description:** Evaluation of Glycemic Status

**Measure:** Serum Insulin

**Time Frame:** Samples will be measured at baseline and after 12 weeks

**Description:** (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

**Measure:** The homeostasis model assessment-estimated insulin resistance (HOMA-IR)

**Time Frame:** Assessed at baseline and after 12 weeks

**Description:** Evaluation of Glycemic Status

**Measure:** Hemoglobin A1c level

**Time Frame:** Samples will be measured at baseline and after 12 weeks

**Description:** Evaluation of Glycemic Status

**Measure:** Fasting and Post Prandial Blood Sugar level

**Time Frame:** Samples will be measured at baseline and after 12 weeks

**Description:** Evaluation of kidney function

**Measure:** Serum creatinine

**Time Frame:** Samples will be measured at baseline and after 12 weeks

**Description:** Evaluation of kidney function

**Measure:** Blood Urea Nitrogen Concentration

**Time Frame:** Samples will be measured at baseline and after 12 weeks

**Description:** 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)

**Measure:** eGFR using the MDRD equation

**Time Frame:** Samples will be measured at baseline and after 12 weeks

**Description:** Evaluation of SMg level

**Measure:** Serum Magnesium

**Time Frame:** Samples will be measured at baseline, 6 weeks and 12 weeks

**Description:** Serum Low-density Lipoprotein Cholesterol (LDL-C), High-density Lipoprotein Cholesterol (HDL-C), Total Cholesterol, Triglycerides

**Measure:** Evaluation of Lipid profile

**Time Frame:** Samples will be measured at baseline and after 12 weeks

**Description:** 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

**Measure:** Fatigue Assessment

**Time Frame:** Assessed at baseline and after 12 weeks

**Description:** Quality of Life (QoL) assessment using D-39 Questionnaire

**Measure:** Quality of Life (QoL) Assessment: D-39 Questionnaire

**Time Frame:** Assessed at baseline and after 12 weeks

### Eligibility Module

**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.

**Maximum Age:** 85 Years

**Minimum Age:** 18 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Locations

**Location 1:**

**City:** Cairo

**Country:** Egypt

**Facility:** Ain Shams University Hospitals

**State:** Abbasseia

**Zip:** 12345

#### Overall Officials

**Official 1:**

**Affiliation:** Faculty of Pharmacy - Ain Shams University

**Name:** Nihal Halawa

**Role:** PRINCIPAL_INVESTIGATOR

### IPD Sharing Statement Module

**IPD Sharing:** NO

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000014570

- Term: Urologic Diseases

- ID: D000052776

- Term: Female Urogenital Diseases

- ID: D000005261

- Term: Female Urogenital Diseases and Pregnancy Complications

- ID: D000091642

- Term: Urogenital Diseases

- ID: D000052801

- Term: Male Urogenital Diseases

- ID: D000048909

- Term: Diabetes Complications

- ID: D000003920

- Term: Diabetes Mellitus

- ID: D000004700

- Term: Endocrine System Diseases

### Condition Browse Module - Browse Branches

- Abbrev: BXS

- Name: Urinary Tract, Sexual Organs, and Pregnancy Conditions

- Abbrev: All

- Name: All Conditions

- Abbrev: BC19

- Name: Gland and Hormone Related Diseases

- Abbrev: BC18

- Name: Nutritional and Metabolic Diseases

### Condition Browse Module - Browse Leaves

- ID: M10698

- Name: Kidney Diseases

- Relevance: HIGH

- As Found: Nephropathy

- ID: M7123

- Name: Diabetic Nephropathies

- Relevance: HIGH

- As Found: Diabetic Nephropathy

- ID: M17319

- Name: Urologic Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M2875

- Name: Urogenital Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M27093

- Name: Female Urogenital Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M14127

- Name: Pregnancy Complications

- Relevance: LOW

- As Found: Unknown

- ID: M8399

- Name: Female Urogenital Diseases and Pregnancy Complications

- Relevance: LOW

- As Found: Unknown

- ID: M27095

- Name: Male Urogenital Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M7115

- Name: Diabetes Mellitus

- Relevance: LOW

- As Found: Unknown

- ID: M26004

- Name: Diabetes Complications

- Relevance: LOW

- As Found: Unknown

- ID: M7862

- Name: Endocrine System Diseases

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000007674

- Term: Kidney Diseases

- ID: D000003928

- Term: Diabetic Nephropathies

### Intervention Browse Module - Ancestors

- ID: D000002400

- Term: Cathartics

- ID: D000005765

- Term: Gastrointestinal Agents

- ID: D000045505

- Term: Physiological Effects of Drugs

### Intervention Browse Module - Browse Branches

- Abbrev: Hypo

- Name: Hypoglycemic Agents

- Abbrev: All

- Name: All Drugs and Chemicals

- Abbrev: AnCoag

- Name: Anticoagulants

- Abbrev: Gast

- Name: Gastrointestinal Agents

- Abbrev: Ot

- Name: Other Dietary Supplements

- Abbrev: Mi

- Name: Mineral

### Intervention Browse Module - Browse Leaves

- ID: M10365

- Name: Insulin

- Relevance: LOW

- As Found: Unknown

- ID: M10054

- Name: Hypoglycemic Agents

- Relevance: HIGH

- As Found: Omegaven

- ID: M173166

- Name: Insulin, Globin Zinc

- Relevance: LOW

- As Found: Unknown

- ID: M21320

- Name: Citric Acid

- Relevance: LOW

- As Found: Unknown

- ID: M1837

- Name: Sodium Citrate

- Relevance: LOW

- As Found: Unknown

- ID: M209491

- Name: Magnesium citrate

- Relevance: HIGH

- As Found: Adolescence

- ID: M27664

- Name: Laxatives

- Relevance: LOW

- As Found: Unknown

- ID: M5651

- Name: Cathartics

- Relevance: LOW

- As Found: Unknown

- ID: M8881

- Name: Gastrointestinal Agents

- Relevance: LOW

- As Found: Unknown

- ID: T382

- Name: Citrate

- Relevance: HIGH

- As Found: Free

- ID: T342

- Name: Magnesium Supplement

- Relevance: LOW

- As Found: Unknown

### Intervention Browse Module - Meshes

- ID: D000007004

- Term: Hypoglycemic Agents

- ID: C000110422

- Term: Magnesium citrate

### Misc Info Module

- Version Holder: 2024-05-24
