Effect of Dietary Magnesium Supplementation vs. Dapagliflozin in Patients With Diabetic Kidney Disease (DKD)
Study Details
Study Description
Brief Summary
This is a prospective, randomized double blind placebo controlled parallel group trial to assess the effect of Effervescent calcium magnesium citrate (EffCaMgCitrate) and dapagliflozin on surrogate markers of kidney and cardiovascular health in patients with stage 3b-4 Chronic Kidney Disease (CKD).
Randomization:
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Placebo EffCaMgCitrate + Placebo Dapagliflozin BID (bis in die / two times)
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EffCaMgCitrate 480mg Mg (total dosage per day) + Placebo Dapagliflozin BID
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Dapagliflozin 10mg (total dosage per day) + Placebo EffCaMgCitrate BID
This study includes three clinic in person visits and weekly telephone visits for 24 weeks.
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Recruit 30 patients with CKD stages 3b-4 and randomize them in double-blind fashion to either placebo, CaMgcitrate 480mg Mg or dapagliflozin 10mg twice daily for 24 weeks
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Determine the effect of interventions on the primary outcome variable serum klotho measured by immunoprecipitation-immunoblot
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Determine the effect of interventions on magnesium.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Placebo Comparator: Group 1: Placebo EffCaMgCitrate + Placebo Dapagliflozin Group 1 will receive a Placebo form the Effervescent CaMgCitrate and a Placebo form of the Dapagliflozin twice a day. |
Dietary Supplement: Placebo EffCaMgCitrate
Placebo Effervescent calcium magnesium citrate ( EffCaMgCitrate) (480mg) to be ingested orally after dissolving in water twice daily.
Drug: Placebo Dapagliflozin
Placebo Dapagliflozin tablets (10 mg) will be administered orally with 8 oz water.
|
| Experimental: Group 2: EffCaMgCitrate + Placebo Dapagliflozin Group 2 will receive the medication EffCalMgcitrate 480mg (total dosage per day) and Placebo Dapagliflozin twice a day. |
Dietary Supplement: EffCaMgCitrate 480 mg
Effervescent calcium magnesium citrate ( EffCaMgCitrate) is a powder mixture of calcium carbonate, trimagnesium dicitrate, and citric acid monohydrate, to be ingested orally after dissolving in water twice daily.
Other Names:
Drug: Placebo Dapagliflozin
Placebo Dapagliflozin tablets (10 mg) will be administered orally with 8 oz water.
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| Experimental: Group 3: Dapagliflozin + Placebo EffCaMgCitrate Group 3 will receive the medication Dapagliflozin10mg (total dosage per day) and Placebo Effervescent CaMgCitrate twice a day. |
Drug: Dapagliflozin 10 mg
Dapagliflozin tablets containing 10 mg will be administered orally with 8 oz water.
Dietary Supplement: Placebo EffCaMgCitrate
Placebo Effervescent calcium magnesium citrate ( EffCaMgCitrate) (480mg) to be ingested orally after dissolving in water twice daily.
|
Outcome Measures
Primary Outcome Measures
- Change in serum klotho levels at 12 weeks [Baseline, 12 weeks]
Change in serum klotho levels in participants with advanced Diabetic Kidney Disease (DKD) at 12 weeks are measured by immunoprecipitation-immunoblot.
- Change in serum klotho levels at 24 week [Baseline, 24 weeks]
Change in Serum klotho levels in participants with advanced Diabetic Kidney Disease (DKD) at 24 weeks are measured by immunoprecipitation-immunoblot.
Secondary Outcome Measures
- Change in serum magnesium levels at 12 weeks [Baseline, 12 weeks]
Mean change from baseline in serum magnesium levels at 12 weeks is measured. Serum magnesium levels are measured by measuring the level of magnesium in the blood.
- Change in serum magnesium levels at 24 weeks [Baseline, 24 weeks]
Mean change from baseline in serum magnesium levels at 24 weeks is measured. Serum magnesium levels are measured by measuring the level of magnesium in the blood.
Eligibility Criteria
Criteria
Inclusion Criteria:
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18-80 years of age
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All races and ethnicities
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All genders
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Type 2 diabetes mellitus
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History of hypertension defined as > 130 or > 80 mmHg or normotensive on pharmacologic therapy
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Estimated glomerular filtration rate (GFR) (CKD Epi equation) of 15-44 ml/min/1.73 m2 (Stages 3b-4 CKD)
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Urinary albumin creatinine ratio of > 200 mg/g <5000mg/g
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Serum magnesium level at screening of > 1.3 mg/dl
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Ability of study participant or legally authorized representative to provide informed written consent
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Able to maintain stable dose of any vitamin D and any calcium supplements for 180 days post randomization.
Exclusion Criteria:
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Autosomal dominant or autosomal recessive polycystic kidney disease, lupus nephritis or anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis
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Receiving cytotoxic therapy, immunosuppressive therapy or other immunotherapy for primary or secondary renal disease within 6 months prior to enrolment
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History of organ transplantation
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Receiving therapy with a sodium glucose co-transporter 2 (SGLT2) inhibitor within 8 weeks prior to enrolment or previous intolerance of an SGLT2 inhibitor
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Type 1 diabetes (T1D)
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Active use of either dapagliflozin or magnesium supplements
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Inability to temporarily discontinue magnesium of calcium supplements
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History of persistent hypercalcemia (serum total Calcium > 10.5 mg/dl)
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History of persistent hypermagnesemia (serum Mg > 3.0 mg/dl)
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Body mass index > 45 kg/m2
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Intolerance to magnesium supplementation
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Active on kidney transplant list
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Inability to provide informed consent
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Any condition outside the renal and cardiovascular disease area, such as but not limited to malignancy, with a life expectancy of less than 2 years based on investigator´s clinical judgement
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Active malignancy requiring treatment at the time of screening (with the exception of successfully treated basal cell or treated squamous cell carcinoma).
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Hepatic impairment (aspartate transaminase [AST] or alanine transaminase [ALT] >3x the upper limit of normal [ULN]; or total bilirubin >2x ULN at time of enrolment)
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Women of child-bearing potential (ie, those who are not chemically or surgically sterilized or who are not post-menopausal) who are not willing to use a medically accepted method of contraception that is considered reliable in the judgment of the investigator or women who have a positive pregnancy test at enrolment or randomization or women who are breast-feeding
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Participation in another clinical study with an investigational product (IP) during the last month prior to Enrolment
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Inability of the patient, in the opinion of the investigator, to understand and/or comply with IP, procedures and/or follow-up OR any conditions that, in the opinion of the investigator, may render the patient unable to complete the study. Patients who cannot complete the patient reported outcome (PRO) assessments can still participate in the study
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Treatment with adrenocorticosteroids or aluminum-containing antacids or drugs
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | UT Southwestern Medical Center | Dallas | Texas | United States | 75390 |
Sponsors and Collaborators
- University of Texas Southwestern Medical Center
Investigators
- Principal Investigator: Robert Toto, MD, UT Southwestern Medical Center
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- STU-2021-0492