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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Heart Failure; Magnesium Deficiency
• Intervention / Treatment: Drug: Magnesium Oxide; Drug: Placebo Oral Tablet

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 320
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Michael Shechter, MD; Phone Number: +97235302617; Email: Michael.Shechter@sheba.health.gov.il
• Study Contact Backup: Name: Nava Eizenberg, RN; Phone Number: +97235302617; Email: Nava.Eizenberg@sheba.health.gov.il

Study Locations

• Israel
  • Ramat Gan, Israel
    • Recruiting
    • Leviev Heart Center, Chaim Sheba Medical Center
    • Contact: Michael Shechter, MD; Phone Number: +97235302617; Email: Michael.Shechter@sheba.health.gov.il

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Sheba Medical Center
• Collaborators: Naveh Pharma (1996) Ltd.
• Investigators: Principal Investigator: Michael Shechter, MD, Sheba Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): August 25, 2019
• Primary Completion (Estimated): January 1, 2026
• Study Completion (Estimated): March 1, 2026

Study Registration Dates

• First Submitted: February 9, 2019
• First Submitted That Met QC Criteria: February 12, 2019
• First Posted (Actual): February 15, 2019

Study Record Updates

• Last Update Posted (Estimated): December 12, 2023
• Last Update Submitted That Met QC Criteria: December 10, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: heart failure; magnesium
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Nutrition Disorders; Deficiency Diseases; Malnutrition; Heart Failure; Magnesium Deficiency; Molecular Mechanisms of Pharmacological Action; Gastrointestinal Agents; Antacids; Magnesium Oxide
• Other Study ID Numbers: SHEBA-18-5464-MS-CTIL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No