<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03824379</url>
  </required_header>
  <id_info>
    <org_study_id>PHCL932</org_study_id>
    <nct_id>NCT03824379</nct_id>
  </id_info>
  <brief_title>Magnesium Supplementation in Diabetic Nephropathy</brief_title>
  <official_title>The Impact of Magnesium Supplementation on the Clinical Outcome of Patients of Diabetic Nephropathy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Ain Shams University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Ain Shams University</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Higher prevalence of hypomagnesaemia in diabetic patients with nephropathy was compared to&#xD;
      those without nephropathy. Serum magnesium levels were significantly inversely correlated&#xD;
      with serum creatinine and U-A/C ratio, and positively correlated with glomerular filtration&#xD;
      rate (GFR).&#xD;
&#xD;
      Hence, Magnesium supplementation using magnesium salts could be a good approach to improve&#xD;
      the cardiovascular complications, insulin resistance index, lipid profile and kidney function&#xD;
      in diabetic nephropathy patients.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Diabetic nephropathy is a serious kidney-related complication of type 1 diabetes and type 2&#xD;
      diabetes. It is also called diabetic kidney disease. Up to 40 percent of people with diabetes&#xD;
      eventually develop kidney disease. Over time, elevated blood sugar associated with&#xD;
      uncontrolled diabetes causes high blood pressure which in turn damages the kidneys by&#xD;
      increasing kidney filtration pressure. Complications of diabetic nephropathy include heart&#xD;
      and blood vessel disease (cardiovascular disease), fluid retention and hyperkalemia.&#xD;
      Magnesium (Mg) is the fourth most abundant cation in the body and the second most important&#xD;
      intracellular cation. It plays an essential role in biological systems as co-factor for more&#xD;
      than 300 essential enzymatic reactions such as signal transduction, energy metabolism,&#xD;
      vascular processes and bone metabolism. Normal serum Mg concentrations ranges from 0.7 to 1.1&#xD;
      mmol/L (1.4-2.0 mEq/L or 1.7-2.4 mg/dL). Outcome studies in the general population have&#xD;
      indicated potential associations between low serum Mg levels and atherosclerosis,&#xD;
      hypertension, diabetes, and left ventricular hypertrophy, as well as both CVD mortality and&#xD;
      all-cause mortality. Low SMg levels (1.4-1.9 mg/dL; 0.58-0.78 mM) were independently&#xD;
      associated with all-cause death in patients with prevalent CKD. Higher prevalence of&#xD;
      hypomagnesaemia in diabetic patients with nephropathy compared to those without nephropathy.&#xD;
      Serum magnesium levels were significantly inversely correlated with serum creatinine and&#xD;
      U-A/C ratio, and positively correlated with glomerular filtration rate (GFR). Magnesium&#xD;
      deficiency promotes hydroxyapatite formation and calcification of vascular smooth muscle&#xD;
      cells . It is closely related to insulin resistance and metabolic syndrome. A lower Mg level&#xD;
      is directly associated with a faster deterioration of renal function in T2DM patients.&#xD;
      Moreover, hypomagnesemia is associated with the long-term micro- and macrovascular&#xD;
      complications of T2DM. A dysregulation of mineral metabolism, reflected by altered levels of&#xD;
      magnesium and FGF-23, correlates with an increased urinary albumin to creatinine ratio (UACR)&#xD;
      in type 2 diabetic patients with CKD stages 2-4. Also, a link between hypomagnesemia and&#xD;
      atherogenic dyslipidemia alterations exists; a significantly raised total cholesterol and LDL&#xD;
      and non-HDL in patients with CKD are observed, suggesting a link to increased cardiovascular&#xD;
      risk in CKD patients. Increasing magnesium levels could attenuate the cardiovascular risk&#xD;
      derived from hyperphosphatemia, hence the CKD progression. Current literature suggests that&#xD;
      Mg may have a protective effect on the CV system. Mg supplementation improves the insulin&#xD;
      resistance index and beta-cell function, and decreases hemoglobin A1c levels in type 2 DM&#xD;
      patients. In animal models of vascular calcification VC, dietary supplementation with&#xD;
      magnesium results in marked reduction in VC and mortality, improved mineral metabolism,&#xD;
      including lowering of PTH, as well as improvement in renal function. Hence, Magnesium&#xD;
      supplementation using magnesium salts could be a good approach to improve the cardiovascular&#xD;
      complications, insulin resistance index, lipid profile and kidney function in diabetic&#xD;
      nephropathy patients.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">June 1, 2019</start_date>
  <completion_date type="Actual">March 1, 2020</completion_date>
  <primary_completion_date type="Actual">March 1, 2020</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>prospective randomized controlled open label study</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change of Human Serum Osteocalcin level</measure>
    <time_frame>Change from baseline Human Serum Osteocalcin level at 12 weeks</time_frame>
    <description>Evaluation of the extent of cardiovadcular events</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Serum Insulin</measure>
    <time_frame>Samples will be measured at baseline and after 12 weeks</time_frame>
    <description>Evaluation of Glycemic Status</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The homeostasis model assessment-estimated insulin resistance (HOMA-IR)</measure>
    <time_frame>Assessed at baseline and after 12 weeks</time_frame>
    <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 &lt;2.5</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Hemoglobin A1c level</measure>
    <time_frame>Samples will be measured at baseline and after 12 weeks</time_frame>
    <description>Evaluation of Glycemic Status</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Fasting and Post Prandial Blood Sugar level</measure>
    <time_frame>Samples will be measured at baseline and after 12 weeks</time_frame>
    <description>Evaluation of Glycemic Status</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Serum creatinine</measure>
    <time_frame>Samples will be measured at baseline and after 12 weeks</time_frame>
    <description>Evaluation of kidney function</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Blood Urea Nitrogen Concentration</measure>
    <time_frame>Samples will be measured at baseline and after 12 weeks</time_frame>
    <description>Evaluation of kidney function</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>eGFR using the MDRD equation</measure>
    <time_frame>Samples will be measured at baseline and after 12 weeks</time_frame>
    <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)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Serum Magnesium</measure>
    <time_frame>Samples will be measured at baseline, 6 weeks and 12 weeks</time_frame>
    <description>Evaluation of SMg level</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evaluation of Lipid profile</measure>
    <time_frame>Samples will be measured at baseline and after 12 weeks</time_frame>
    <description>Serum Low-density Lipoprotein Cholesterol (LDL-C), High-density Lipoprotein Cholesterol (HDL-C), Total Cholesterol, Triglycerides</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Fatigue Assessment</measure>
    <time_frame>Assessed at baseline and after 12 weeks</time_frame>
    <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.&#xD;
&gt; 4 points indicates no fatigue 4 points or more indicates increasing fatigue</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of Life (QoL) Assessment: D-39 Questionnaire</measure>
    <time_frame>Assessed at baseline and after 12 weeks</time_frame>
    <description>Quality of Life (QoL) assessment using D-39 Questionnaire</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">60</enrollment>
  <condition>Diabetic Nephropathies</condition>
  <arm_group>
    <arm_group_label>Magnesium arm</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>30 patients will receive the standard therapy (anti-diabetic ) + magnesium supplement</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>30 patients will receive the standard therapy (anti-diabetic)</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Magnesium citrate</intervention_name>
    <description>magnesium citrate equivalent 20-30 mmol elemental magnesium</description>
    <arm_group_label>Magnesium arm</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Antidiabetic</intervention_name>
    <description>insulin or oral hypoglycemics</description>
    <arm_group_label>Control</arm_group_label>
    <arm_group_label>Magnesium arm</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Age ≥ 18 years.&#xD;
&#xD;
          2. Type I or II diabetic patientCKD stage 3 ( eGFR = 30 - 59 ml/min) or stage 4 ( eGFR&#xD;
             15-29 ml/min)&#xD;
&#xD;
          3. Proteinuria 30-300 mg/dl (microalbuminuria)&#xD;
&#xD;
          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&#xD;
             mmol/L; 1.4-2.0 mEq/L).&#xD;
&#xD;
          5. Life expectancy &gt;12 months.&#xD;
&#xD;
          6. Women of child-bearing age should be using contraceptives as Hormonal contraceptive or&#xD;
             Intra-uterine device.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Kidney donor recipient.&#xD;
&#xD;
          2. Current treatment with Mg supplements.&#xD;
&#xD;
          3. Any condition impairing intestinal absorption of Mg (e.g: chronic pancreatitis, short&#xD;
             bowel syndrome)&#xD;
&#xD;
          4. Active malignancy.&#xD;
&#xD;
          5. Pregnancy or breastfeeding.&#xD;
&#xD;
          6. Cardiac Arrythmias.&#xD;
&#xD;
          7. Allergy towards the Mg supplement.&#xD;
&#xD;
          8. Participation in other interventional trials.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>85 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Nihal Halawa</last_name>
    <role>Principal Investigator</role>
    <affiliation>Faculty of Pharmacy - Ain Shams University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Ain Shams University Hospitals</name>
      <address>
        <city>Cairo</city>
        <state>Abbasseia</state>
        <zip>12345</zip>
        <country>Egypt</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Egypt</country>
  </location_countries>
  <verification_date>January 2021</verification_date>
  <study_first_submitted>January 26, 2019</study_first_submitted>
  <study_first_submitted_qc>January 29, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 31, 2019</study_first_posted>
  <last_update_submitted>January 11, 2021</last_update_submitted>
  <last_update_submitted_qc>January 11, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">January 12, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Ain Shams University</investigator_affiliation>
    <investigator_full_name>Nihal Mohamed Halawa</investigator_full_name>
    <investigator_title>clinical Pharmacist</investigator_title>
  </responsible_party>
  <keyword>magnesium</keyword>
  <keyword>diabetic nephropathy</keyword>
  <keyword>osteocalcin</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Kidney Diseases</mesh_term>
    <mesh_term>Diabetic Nephropathies</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hypoglycemic Agents</mesh_term>
    <mesh_term>Magnesium citrate</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03824379
org study id: PHCL932
nct id: NCT03824379
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
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.
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.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: prospective randomized controlled open label study
primary purpose: Treatment
masking: None (Open Label)
measure: Change of Human Serum Osteocalcin level
time frame: Change from baseline Human Serum Osteocalcin level at 12 weeks
description: Evaluation of the extent of cardiovadcular events
measure: Serum Insulin
time frame: Samples will be measured at baseline and after 12 weeks
description: Evaluation of Glycemic Status
measure: The homeostasis model assessment-estimated insulin resistance (HOMA-IR)
time frame: Assessed 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: 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 Glycemic Status
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
measure: eGFR using the MDRD equation
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: Serum Magnesium
time frame: Samples will be measured at baseline, 6 weeks and 12 weeks
description: Evaluation of SMg level
measure: Evaluation of Lipid profile
time frame: Samples will be measured at baseline and after 12 weeks
description: Serum Low-density Lipoprotein Cholesterol (LDL-C), High-density Lipoprotein Cholesterol (HDL-C), Total Cholesterol, Triglycerides
measure: Fatigue Assessment
time frame: Assessed 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: Quality of Life (QoL) Assessment: D-39 Questionnaire
time frame: Assessed at baseline and after 12 weeks
description: Quality of Life (QoL) assessment using D-39 Questionnaire
arm group label: Magnesium arm
arm group type: Experimental
description: 30 patients will receive the standard therapy (anti-diabetic ) + magnesium supplement
arm group label: Control
arm group type: Active Comparator
description: 30 patients will receive the standard therapy (anti-diabetic)
intervention type: Dietary Supplement
intervention name: Magnesium citrate
description: magnesium citrate equivalent 20-30 mmol elemental magnesium
arm group label: Magnesium arm
intervention type: Drug
intervention name: Antidiabetic
description: insulin or oral hypoglycemics
arm group label: Control
arm group label: Magnesium arm
criteria: 
gender: All
minimum age: 18 Years
maximum age: 85 Years
healthy volunteers: No
last name: Nihal Halawa
role: Principal Investigator
affiliation: Faculty of Pharmacy - Ain Shams University
facility: 
country: Egypt
responsible party type: Principal Investigator
investigator affiliation: Ain Shams University
investigator full name: Nihal Mohamed Halawa
investigator title: clinical Pharmacist
mesh term: Kidney Diseases
mesh term: Diabetic Nephropathies
mesh term: Hypoglycemic Agents
mesh term: Magnesium citrate
sharing ipd: No