Effect of Melatonin on Cardiovascular and Muscle Mass and Function in Patients With Heart Failure

Study Overview
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Brief Summary
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The main aim of this study is to investigate the effect of melatonin on clinical outcome, quality of life, and cardiovascular function of the patients with heart failure, as well as its effect on their skeletal muscle mass and function.

Detailed Description
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People with heart failure (HF) suffer from various comorbidities and complications which their management is as important as treatment of HF per se. An important complication of the HF is progressive decrease in muscle mass and function known as muscle wasting or sarcopenia. Prevention, diagnosis, and treatment of muscle wasting is emphasized to improve prognosis and quality of life of the patients with HF. Melatonin is a natural hormone which is secreted from pineal gland and is involved in circadian rhythm control. Recent data delineates more important roles for melatonin in cellular metabolism and apoptosis, as well as acting as an antioxidant and anti-inflammatory agent in the body. Experimental studies show that melatonin can have a beneficial role in muscle wasting in several chronic conditions such as heart failure. Furthermore melatonin has been shown to have valuable effects on cardiovascular health, blood pressure, and endothelial function and it might benefit patients with heart failure. In this study the effect of melatonin on clinical outcome and quality of life of the patients with HF and their echocardiographic parameters, muscle mass, muscle function, inflammatory biomarkers, serum metabolic parameters, and serum oxidative stress markers will be studied.

Official Title
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Effect of Melatonin on Cardiovascular and Muscle Function in Patients With Heart Failure: a Double Blinded Prospective Randomized Clinical Trial.

Conditions
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Heart Failure With Reduced Ejection Fraction

Intervention / Treatment
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* Drug: Melatonin 10 mg
* Drug: Placebo Oral Tablet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Systolic heart failure with ejection fraction < 40, either ischemic or dilated cardiomyopathy (DCM) Symptoms and medications of HF have been stable for at least three months NYHA class II-III Willing to participate in the study and providing informed consent Exclusion Criteria: Chronic comorbidities: insulin dependent diabetes, renal failure (GFR < 30 mL/min per 1.73 m2), uncontrolled endocrine disease, end-stage liver disease, rheumatological disease, chronic obstructive pulmonary disease (class D according to GOLD classification), morbid obesity (BMI > 35) Acute ischemic heart event or revascularization procedure in the last month Regular supervised exercise or ingestion of muscle hypertrophy supplementations in the last three months Vegetarian diet or sever restriction of protein in the diet in the last three months Occurrence of melatonin related adverse effects

Ages Eligible for Study
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Minimum Age: 30 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
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Melatonin<br>Melatonin (10 mg tablets) by oral root, ingested at bedtime for 6 months | Drug: Melatonin 10 mg<br>* Melatonin tablets (10 mg)<br>|
| Placebo Comparator: Placebo<br>Placebo tablets in the same shape as melatonin tablets, ingested the same as the melatonin tablets. | Drug: Placebo Oral Tablet<br>* Placebo tablets manufactured the same as melatonin tablets<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Composite clinical endpoint score | A score with the following components: all-cause mortality, hospitalization for heart failure during the study, and change in quality of life by Minnesota Living with Heart Failure Questionnaire (MLHFQ) | 6 months or earlier if patient was dropped out from the study | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse effects of melatonin | Adverse effects detected in the melatonin group compared with the placebo group | Throughout the study up to 6 months | 
| Change in appendicular lean mass (kg) | Measured by dual-energy x-ray absorptiometry | Baseline and 6 months | 
| Change in lean body mass (kg) | Measured by bioimpedance analysis | Baseline and 3 months | 
| Change in lean body mass (kg) | Measured by bioimpedance analysis | Baseline and 6 months | 
| Change in grip strength (kg) | Measured by a hydraulic dynamometer | Baseline and 3 months | 
| Change in grip strength (kg) | Measured by a hydraulic dynamometer | Baseline and 6 months | 
| Change in exercise capacity | Measured by 6 minute walk test | Baseline and 3 months | 
| Change in exercise capacity | Measured by 6 minute walk test | Baseline and 6 months | 
| Change in Left ventricular ejection fraction (LVEF) | Measured by echocardiography using the Simpson method | Baseline and 6 months | 
| Change in left ventricular end-systolic volume (LVESV) | Measured by echocardiography using the Simpson method | Baseline and 6 months | 
| Change in endothelial dysfunction | Measured by flow-mediated vasodilation (FMD) method | Baseline and 6 months | 
| Change in mean systolic and diastolic blood pressures | Mean of two measurements, using an automated electronic oscillometric device | Baseline and 3 months | 
| Change in mean systolic and diastolic blood pressures | Mean of two measurements, using an automated electronic oscillometric device | Baseline and 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Heart failure, Melatonin, Muscle wasting