Heart Failure With Reduced Ejection Fraction
Conditions
Keywords
Heart failure, Melatonin, Muscle wasting
Brief summary
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
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.
Interventions
DRUGMelatonin 10 mg
Melatonin tablets (10 mg)
DRUGPlacebo Oral Tablet
Placebo tablets manufactured the same as melatonin tablets
Sponsors
National Institute for Medical Research Development
Isfahan University of Medical Sciences
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
30 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Composite clinical endpoint score | 6 months or earlier if patient was dropped out from the study | 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) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in appendicular lean mass (kg) | Baseline and 6 months | Measured by dual-energy x-ray absorptiometry |
| Change in lean body mass (kg) | Baseline and 3 months | Measured by bioimpedance analysis |
| Change in grip strength (kg) | Baseline and 3 months | Measured by a hydraulic dynamometer |
| Change in exercise capacity | Baseline and 3 months | Measured by 6 minute walk test |
| Change in Left ventricular ejection fraction (LVEF) | Baseline and 6 months | Measured by echocardiography using the Simpson method |
| Change in left ventricular end-systolic volume (LVESV) | Baseline and 6 months | Measured by echocardiography using the Simpson method |
| Change in endothelial dysfunction | Baseline and 6 months | Measured by flow-mediated vasodilation (FMD) method |
| Change in mean systolic and diastolic blood pressures | Baseline and 3 months | Mean of two measurements, using an automated electronic oscillometric device |
| Adverse effects of melatonin | Throughout the study up to 6 months | Adverse effects detected in the melatonin group compared with the placebo group |
Other
| Measure | Time frame | Description |
|---|---|---|
| Change in serum insulin, and IGF-1 levels | Baseline and 6 months | Measured by enzyme-linked immunosorbent assay (ELISA) on serum samples stored at -80° |
| Change in level of serum inflammatory biomarkers | Baseline and 6 months | Measured by enzyme-linked immunosorbent assay (ELISA) on serum samples stored at -80° |
| Change in level of serum oxidative stress biomarkers | Baseline and 6 months | Including malondialdehyde (MDA) and total antioxidant capacity (TAC) |
| Changes in psychological status of the patients | Baseline and 6 months | Including anxiety (by Spielberger State - Trait Anxiety Inventory (STAI)) and depression (by Beck Depression Inventory) |
| Changes in sleep quality of the patients | Baseline and 6 months | Measured by Pittsburgh Sleep Quality Index (PSQI) questionnaire |
| Change in serum lipid levels (mg/dl) | Baseline and 6 months | Including triglyceride, LDL, and HDL, measured in serum samples after 12h fasting |
| Change in fasting blood glucose level (mg/dl) | Baseline and 6 months | Measured in serum samples after 12h fasting |
Countries
Iran
Contacts
Primary ContactShervin Gh Hoseini, MD, PhD
Backup ContactMasoumeh Sadeghi, MD
Outcome results
None listed