The Effect of MElatonin on Depression, Anxiety, CIrcadian and Sleep Disturbances in Patients After Acute Myocardial Syndrome
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 252
- 试验地点
- 6
- 主要终点
- Major Depression Inventory (MDI)
研究概览
简要总结
The objective of the study is to investigate whether prophylactic treatment with melatonin has an effect on depressive symptoms. Secondarily melatonin's effect on anxiety, sleep and circadian disturbances will be investigated.
The MEDACIS trial is a randomised, placebo-controlled, double-blinded multicenter trial investigating the effect of 25 mg exogenous melatonin (intervention group) against placebo (control group) and the study is designed as a parallel group superiority trial.
详细描述
AIM Depression after Acute coronary syndrome (ACS - myocardial infarction and unstable angina) is highly prevalent and associated with a 2.5 fold increased in all-cause morbidity and mortality. Sleep disturbances is an integrated part of the pathology of depression and have severe consequences for quality of life.
Melatonin has shown potential to reduce depressive symptoms and anxiety. Likewise melatonin has shown sleep improving effects in several populations and also in patients with depression. Melatonin can potentially reduce the incidence of depression and sleep disturbances in patients after myocardial infarction.
The project sets to answer the following hypotheses:
- Melatonin will due to its antidepressant effect prevent or reduce the incidence of depressive symptoms in patients after an ACS.
- Melatonin will due its anxiolytic effect prevent or reduce the incidence of anxiety in patients after an ACS.
- Melatonin will due to its hypnotic and circadian effects prevent development of sleep and circadian disturbances in patients after an ACS.
BACKGROUND In Denmark about 8600 each year suffered an acute myocardial infarction. An acute myocardial infarction is a life-changing event that affects people's lives long after the blood clot. 20% develop a moderate to severe depression requiring pharmacological treatment and up to 50% experience depressive symptoms after the initial treatment. Depression after a acute coronary syndrome is associated with 2.5-fold increased mortality, and 1.5-fold increased risk of a recurrence of thrombosis. Screening of patients for depression has therefore been recommended by both the Danish cardiology Association and the American Heart Association.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients should be admitted to a coronary care unit for acute coronary syndrome (ACS), and should be enrolled within 4 weeks after the primary ACS.
- •Participants should be 18 years or older.
- •No sign of depression on Major Depression Inventory (MDI) at the point of enrolment.
- •Participants must sign an informed consent form
- •Females not in menopause (defined as no menstruation during the last 12 months) should have a negative pregnancy test.
排除标准
- •Known allergic reaction to melatonin.
- •Ongoing or previous pharmacological treated depression or bipolar disorder.
- •No dementia as determined by mini mental state examination score (MMSE) < 24
- •At the point of inclusion no participation in another pharmacological intervention trial is allowed.
- •No diagnose of Rotor or Dubin-Johnson syndrome, epilepsy, sleep apnoea syndrome, systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) or multiple sclerosis is allowed.
- •Severe liver disease defined as transaminases above X 3 normal levels, and severe kidney disease defined as eGRF under 40 ml/min.
- •Ongoing hypnotic treatment.
- •Known sleep disorder (e.g. insomnia, restless legs etc.)
- •Work involving nightshifts.
- •Daily alcohol consumption above 5 units of alcohol (1 unit = 12 g alcohol)
- •Predictable poor compliance ( e.g. not speaking fluent Danish)
- •Pregnant or breastfeeding.
- •Severe, life-threatening medical condition, that implies that the patient cannot participate in a the study course. (e.g. cancer, stroke, )
- •Indication for coronary artery bypass graft (CABG).
- •For the MEFACS subtrial - (single center)
- •Conditions that preclude/make impossible the measurement of reliable RHI (e.g. patient with only one arm, known side-difference in brachial arterial blood pressure and other factors).
研究组 & 干预措施
Melatonin (N-acetyl-5-methoxytryptamine)
Melatonin (N-acetyl-5-methoxytryptamine) 25 mg oral administration 1 hour before bedtime for 12 weeks.
干预措施: Melatonin (N-acetyl-5-methoxytryptamine) (Drug)
Placebo
Comparable placebo pill, oral administration 1 hour before bedtime for 12 weeks.
干预措施: Placebo (Drug)
结局指标
主要结局
Major Depression Inventory (MDI)
时间窗: Depression at one point in the study (not including baseline) out of 6 measurements at app. day 84
MDI is a self-rating depression scale with 12 questions. Rating scale: No depression - score from 0-20 Mild depression - score from 21-25 Moderate depression - score from 26-30 Severe depression - score from 31-50.
次要结局
- Actigraphy - Sleep outcomes - number of awakenings(From inclusion to first clinical visit (app. 14 days))
- Actigraphy - Sleep outcomes - sleep latency(From inclusion to first clinical visit (app. 14 days))
- Actigraphy - Sleep outcomes - sleep effetiveness(From inclusion to first clinical visit (app. 14 days))
- Actigraphy - Sleep outcomes - wake after sleep onset(From inclusion to first clinical visit (app. 14 days))
- Actigraphy - Sleep outcomes - time awake(From inclusion to first clinical visit (app. 14 days))
- Actigraphy - circadian outcomes - Amplitude(From inclusion to first clinical visit (app. 14 days))
- Actigraphy - Sleep outcomes - total sleep time(From inclusion to first clinical visit (app. 14 days))
- Actigraphy - Sleep outcomes - number of naps(From inclusion to first clinical visit (app. 14 days))
- Subjective sleep quality measured by Pittsburgh sleep quality index (PSQI)(Subjectie sleep at one point in the study (not including baseline) out of 2 measurements at app. day 14 and day 84 of the study)
- VAS Data on Pain(From inclusion to first clinical visit each day (day 0 - 14). After the first clinical visit (day 14) the VAS will be filled out on day 28, day 42, day 56, day 70 and day 84 of the study.)
- Actigraphy - Sleep outcomes - Time in bed(From inclusion to first clinical visit (app. 14 days))
- Actigraphy - Sleep outcomes - time asleep(From inclusion to first clinical visit (app. 14 days))
- Actigraphy - circadian outcomes - Mesor(From inclusion to first clinical visit (app. 14 days))
- Sleep diary(From inclusion to first clinical visit each day (day 0 - 14). After the first clinical visit (day 14) the sleep diary will be filled out on day 28, day 42, day 56, day 70 and day 84 of the study.)
- UKU side effect rating scale(The UKU will be filled out a total of 6 measurements at app. day 14, day 28, day 42, day 56, day 70 and day 84 of the study)
- Endothelial function (EndoPAT)(From inclusion (day 0), first clinical visit (day 14), and final visit (day 84).)
- Actigraphy - circadian outcomes - F-statistics(From inclusion to first clinical visit (app. 14 days))
- Depression measured by Hospital anxiety and depression scale (HADS-D)(Depression at one point in the study (not including baseline) out of 2 measurements at app. day 14 and day 84 of the study)
- VAS Data on Sleep Quality(From inclusion to first clinical visit each day (day 0 - 14). After the first clinical visit (day 14) the VAS will be filled out on day 28, day 42, day 56, day 70 and day 84 of the study.)
- Actigraphy - circadian outcomes - Acrophase(From inclusion to first clinical visit (app. 14 days))
- Actigraphy - circadian outcomes - Inter-daily stability(From inclusion to first clinical visit (app. 14 days))
- Actigraphy - circadian outcomes - Inter-daily variability(From inclusion to first clinical visit (app. 14 days))
- Anxiety measured by Hospital anxiety and depression scale (HADS-A)(Anxiety at one point in the study (not including baseline) out of 2 measurements at app. day 14 and day 84 of the study)
- VAS Data on Anxiety(From inclusion to first clinical visit each day (day 0 - 14). After the first clinical visit (day 14) the VAS will be filled out on day 28, day 42, day 56, day 70 and day 84 of the study.)
- VAS Data on Fatigue(From inclusion to first clinical visit each day (day 0 - 14). After the first clinical visit (day 14) the VAS will be filled out on day 28, day 42, day 56, day 70 and day 84 of the study.)
- VAS Data on General Well-being(From inclusion to first clinical visit each day (day 0 - 14). After the first clinical visit (day 14) the VAS will be filled out on day 28, day 42, day 56, day 70 and day 84 of the study.)