The Impact of Magnesium on Exercise Tolerance, Quality of Life and Clinical Outcomes in Chronic Heart Failure Patients

Study Overview
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Brief Summary
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Magnesium supplementation could improve cardiac performance. Patients with chronic heart failure (CHF) are magnesium deficient and we hypothesized that 1 year supplementation of oral magnesium comparted to placebo will improve exercise duration time and quality of life.

Detailed Description
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Magnesium supplementation improves myocardial metabolism, inhibits calcium accumulation and myocardial cell death; it improves vascular tone, peripheral vascular resistance, afterload and cardiac output, reduces cardiac arrhythmias and improves lipid metabolism. Magnesium also reduces vulnerability to oxygen-derived free radicals, improves human endothelial function and inhibits platelet function. Patients with chronic heart failure (CHF) are magnesium deficient. The activation of the renin-angiotensin-aldosterone system and the use of diuretics are associated with depletion of potassium and magnesium in CHF. Magnesium deficiency stimulates aldosterone production and secretion, while magnesium infusion decreases aldosterone production production by inhibiting cellular calcium influx. Adamopoulos et al recently found that CHF in patients [mainly New York Heart Association (NYHA) II-II] with low serum magnesium ≤ 2 mEq/L was associated with increased cardiovascular mortality (but had no association with cardiovascular hospitalization) compared to those with serum magnesium > 2 mEq/L in a long-term follow-up of 36 months, suggesting that most of these deaths were likely sudden (arrhythmic) in nature. Furthermore, Stepura and Martynow demonstrated that oral magnesium orotate used as adjuvant therapy in severe NYHA IV CHF patients increased 1-year survival rate and improved clinical symptoms and patient's quality of life compared to placebo. The investigators hypothesized that 1-year supplementation of oral magnesium compared to placebo to CHF patients will improve exercise duration time and quality of life.

Official Title
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The Impact of Magnesium Oxide Monohydrate Compared to Placebo on Exercise Tolerance, Quality of Life and Clinical Outcomes in Chronic Heart Failure Patients

Conditions
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Magnesium Deficiency, Heart Failure

Intervention / Treatment
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* Drug: Placebo Oral Tablet
* Drug: Magnesium Oxide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: CHF patients NYHA II-IV > 3 months Diuretic therapy > 3 months Signed informed consent Exclusion Criteria: chronic renal failure (serum creatinine > 3 mg/dL) AMI/ACS< 3 months from randomization Cardiac or other organ transplantation Uncontrolled hypo/hyperthyroidism Chronic diarrhea Life expectancy < 1 year Known psychiatric disease which inhibits patient's enrollment to the study Inability to come for follow-up visits Any planned operation/invasive procedures in the near 6 months Uncontrolled cardiac arrhythmias Inability to perform 6 minute walk testing Any participation in another interventional clinical trial < 1 month from randomization Any malignancy with life expectancy < 1 year Any AV Block> 2 degree without a pacemaker

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: The aim of the study is to test The impact of magnum versus placebo, on six-minute and clinical outcomes of patients with CHF (level 2-4). The Primary endpoints are: Improvement in Six-Minute walk test. Improvement in clinical outcomes: death, CHF hospitalization, revascularization etc. To test the hypothesis that the six-minute results between the two study groups are different, with significance level of 5% and power of at least 80%, we use the t-test. Based on Monica et al (2001), the mean six-minute results among these patients is 218 with SD=28. for an expected difference of at least 10 meter, we need a sample size of 125 patients in each group.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Magnesium<br>oral magnesium oxide tablets [Magnox 520 TM (magnesium oxide monohydrate, 520 mg/day of elemental magnesium), Naveh Pharma, Israel] | Drug: Magnesium Oxide<br>* Magnesium tablets<br>* Other names: Magnox 520 TM;|
| Placebo Comparator: Placebo<br>Placebo tablets | Drug: Placebo Oral Tablet<br>* Placebo tablets<br>* Other names: Placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Improvement in exercise duration time | Improvement in 6-minute walking testing (any improvemnt of length in meters from baseline). The outcome will be measured in meters and the higher is better from baseline. A 10% higher distance from baseline will be considered significant improvement. | 1 year | 
| Qaulity of life | Improvement in quality of life by Minisota living with Heart Failure Questionnaire. The scale is in points and the higher scale the better. Any improvement in at least 10% from baseline will be considered a significant improvement. | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Improvment in the number of hospitalizations for heart failure | All hospitalizations for worsening of heart failure will be counted and recorded and the number of hospitalizations for heart failure will be conted in the magnesium compared to the placebo arms. | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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magnesium, heart failure