Clinical trial NCT04942119: Impact of Long-term Serum Magnesium and Potassium Levels Optimization and Multifactorial Adherence Intervention on the Progression of Diabetic Kidney Disease.
Official title: Impact of Long-term Serum Magnesium and Potassium Levels Optimization and Multifactorial Adherence Intervention on the Progression of Diabetic Kidney Disease.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Diabetic Kidney Disease
Potassium Imbalance
Magnesium Deficiency
Keywords: Diabetic kidney disease, Magnesium, Potassium, medication adherence, diet adherence, mobile application, fixed medication possession ratio.
Lead sponsor: United Arab Emirates University
Sponsor class: OTHER
First posted: 2021-06-28
Enrollment: 160
Sex: ALL
Minimum age (years): 30
Maximum age (years): 61
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: A randomized, single-blinded, control study of 160 national UAE citizen patients who have been diagnosed with type 2 diabetes mellitus and will attend the endocrinology or chronic disease clinic (CDC) and having follow-up schedules in an ambulatory healthcare services (AHS) clinic, UAE.
Primary purpose: PREVENTION

Brief summary: Insufficient clinical evidence correlates the progression of diabetic kidney disease with electrolyte homeostasis in patients diagnosed with type 2 diabetes mellitus (T2DM), especially in the United Arab Emirates (UAE) population and what are the most effective interventions to slow chronic renal failure progression.

In our research, we test the hypothesis that low serum magnesium and potassium levels are directly associated with the decline of kidney function in diabetic patients who did not have severely impaired renal function at baseline. In addition, we describe the effect of long-term multifactorial adherence interventions on medication adherence, diet adherence and follow-up visits using a telemedicine approach such as mobile applications in reducing the progression of chronic kidney disease and other diabetes-related complications.

This study is a single-blind randomized control trial to demonstrate the causal relationship between potassium and magnesium levels and estimated glomerular filtration rate (eGFR) decline. The intervention group will be evaluated for manifestations of electrolyte imbalance and correction of serum magnesium and/or potassium levels will be initiated based on the last updated laboratory test. Moreover, they will receive education to reinforce diet and exercise changes at each follow up visit by a specialized dietitian with pharmacist-led comprehensive medication therapy management utilizing multifactorial adherence interventions to measure potential drug-drug or drug-food interactions, as well as medication and follow-up adherence through an integrated mobile application and fixed medication possession ratio (FMPR).

This research is under progress, and summary of its findings will be reported. This study will suggest if additional national monitoring guidelines may be warranted. In addition, it will reduce diabetic burden, medication cost in UAE and improve patient satisfaction by reducing or delaying the progression of diabetic kidney disease in diabetic patients.

Detailed description: Some studies showed that electrolyte homeostasis is altered in diabetic patients compared with non-diabetic patients even in normotensive patients. Serum magnesium and sodium concentrations were found to be decreased and potassium and calcium levels to be increased in patients with diabetes mellitus compared to euglycemic patients (Shahid et al., 2008). Other studies showed that hyperglycemia-induced effects on cellular transport processes and the depression of the function of Sodium-potassium ATPase pump (NaK-ATPase) may play a major role in attenuating electrolyte abnormalities in patients with diabetes (Reza, et al., 2015).

Limited studies were conducted recently to investigate the effectiveness of correcting electrolyte imbalances, including both serum hypomagnesemia and hypokalemia, in improving patients' symptoms during the recovery from acute renal failure. Form several studies, the authors suggested potential avenues of future research to include investigating the effect of treating hypomagnesemia in conjunction with hypokalemia in kidney disease on the progression of diabetic kidney disease. The encouraging results of the mentioned investigation have, consequently, provoked the interest in optimizing serum magnesium and potassium to delay the progression of chronic kidney disease.

Moreover, this research will examine new dimensions of multifactorial intervention approach to the local population of UAE. The research will include dietitians' interventions to enhance adherence to dietary advice, pharmacist-led interventions to evaluate long-term adherence to medication, as well as follow-up schedule including regular laboratory testing to provide regular monitoring of eGFR, and to ensure that the patients are not receiving contraindicated or inappropriately high dose of medication as their eGFR declines in the progression of diabetic kidney.

Research Objectives The proposed research study aims to investigate the impacts of optimizing potassium and magnesium levels and multifactorial intervention including pharmacist-led medication adherence and optimization with dietary and lifestyle counseling on the progression of diabetic kidney disease and other diabetic metabolic outcomes in patients diagnosed with type 2 diabetes mellitus (T2DM) in national UAE population.

Primary Objectives:

1. To evaluate the impact on the progression of diabetic kidney disease through pharmacist-led medication compliance and optimization, along with dietary, exercise and follow-up visits adherence, using multi-intervention approach.
2. To describe the effect of pharmacist led therapy review and adherence, and dietary counseling on electrolyte levels, specifically potassium and magnesium levels.
3. To establish the relationship between serum potassium and magnesium levels and the progression of diabetic kidney disease.

Secondary objectives

1. To assess the influence of the multifactorial interventions on other diabetic outcomes, such as HbA1c level, and other diabetes-related complications.
2. To measure changes in the patient's metabolic panel and electrolyte levels as a consequence of the multifactorial interventions.

Research Overview

The proposed research will target diabetic patients and the progression of diabetic kidney disease, which is one of the most common chronic diseases among UAE citizens. The rate of progression varies considerably between individuals depending on serum electrolyte levels such as serum magnesium and potassium levels, the conventional or multifactorial intervention received, and determinants of adherence early in the course of diabetic disease. The proposed research will investigate the impact of serum magnesium and potassium levels with long-term multifactorial intervention targeting multiple risk factors and adherence on the progression of diabetic kidney disease in UAE citizen patients with type 2 diabetes.

Eligibility criteria: Inclusion Criteria:

1. Male or female UAE citizen patients between 30 and 60 years of age.
2. Patient has been previously diagnosed with type 2 diabetes mellitus recorded in Cerner, defined by diabetes mellitus in our diagnostic criteria
3. Previously on diabetic medication recorded in Cerner and antidiabetic therapy must be unchanged for 12 weeks prior to the study.
4. Patients with normal or mild to moderate magnesium and / or potassium serum levels, as defined in our definition.
5. Patients with normal or mild impaired renal function, defined as glomerular filtration rate more than 30 ml/min and albumin/creatinine ratio ≤ 30 mg/mmol, for more than 3 months as baseline value (Stage G1, G2, G3a and G3b of chronic kidney disease (CKD).
6. Body Mass index less than 40 at study enrollment.

Exclusion Criteria:

1. Non-UAE citizen patients or patients without full insurance coverage.
2. Blood dyscrasias or any disorders causing hemolysis or unstable red blood cell population (e.g., malaria, babesiosis, hemolytic anemia).
3. Patients with severe or symptomatic hypokalemia and/or hypomagnesemia, metabolic acidosis, or hypophosphatemia with or without proximal renal tubular acidosis and Fanconi syndrome, as defined in our definition.
4. Prolonged hypokalemia with surreptitious diuretic use, laxative abuse, eating disorders, or primary aldosteronism.
5. Stage 4 or 5 CKD patients, with severe reduction in glomerular filtration rate, kidney failure or dialysis, defined as GFR ≤ 29 ml/min or albumin/creatinine ratio ˃ 30 mg/mmol as baseline value.
6. High cardiovascular risk (defined as 10-year predicted ASCVD risk ≥7.5% by Pooled Cohort Equation or Framingham Risk Score ≥20%), or cardiac surgery, or angioplasty within the last 12 months or any diabetic macrovascular complications as defined in our definition.
7. Receiving medication that may cause drug-induced acute renal failure during the observational period and may be implicated in hypomagnesemia (such as aminoglycoside antibiotics, cyclosporine, amphotericin B, cisplatin, pentamidine, and foscarnet).
8. Indication of liver disease, defined by serum levels of either alanine aminotransferase (ALT), aspartate aminotransferase (AST) or alkaline phosphatase (ALP) above 3 x upper limit of normal (ULN) as determined at the beginning of the study or within the last 12 months.
9. Bariatric surgery within the past two years and other gastrointestinal surgeries that induce chronic malabsorption.
10. Medical history of cancer and/or treatment for cancer within the last 5 years, or immune compromised patients.
11. Treatment with systemic steroids or change in dosage of thyroid hormones within the last 12 months after starting the study or any other uncontrolled endocrine disorder.
12. Pre-menopausal women who are nursing or pregnant within the last 12 months.
13. Patient with communication barriers that may affect obtaining patient's adherence, receiving diet, exercise counseling or consent signing, and include:

    1. Patients with severe emotional distress.
    2. Patients who are unable to use mobile applications or to access the internet for any reason.

Primary outcomes:
measure: Difference in eGFR
timeFrame: From date of randomization until the end of the follow-up period or date of participant exit for any cause, whichever came first, assessed up to 12 months (during the study follow-up period)
measure: Serum potassium and magnesium levels
timeFrame: From date of randomization until the end of the follow-up period or date of participant exit for any cause, whichever came first, assessed up to 12 months (during the study follow-up period)
measure: Medication adherence
timeFrame: From date of randomization until the end of the follow-up period or date of participant exit for any cause, whichever came first, assessed up to 12 months (during the study follow-up period)
measure: Dietary adherence
timeFrame: From date of randomization until the end of the follow-up period or date of participant exit for any cause, whichever came first, assessed up to 12 months (during the study follow-up period)
measure: Lifestyle adherence
timeFrame: From date of randomization until the end of the follow-up period or date of participant exit for any cause, whichever came first, assessed up to 12 months (during the study follow-up period)
Secondary outcomes:
measure: HbA1c level
timeFrame: From date of randomization until the end of the follow-up period or date of participant exit for any cause, whichever came first, assessed up to 12 months (during the study follow-up period)
measure: Optimal electrolyte levels and metabolic panel
timeFrame: From date of randomization until the end of the follow-up period or date of participant exit for any cause, whichever came first, assessed up to 12 months (during the study follow-up period)
measure: Side effects or complications
timeFrame: From date of randomization until the end of the follow-up period or date of participant exit for any cause, whichever came first, assessed up to 12 months (during the study follow-up period)
Other outcomes:
Locations:
city: Al Ain
country: United Arab Emirates
facility: Oud Al Touba Diagnostic and Screening center, AHS, SEHA.
Study officials:
References: