Ignite Creation Date:
2025-12-25 @ 1:13 AM
Ignite Modification Date:
2025-12-25 @ 11:23 PM
Study NCT ID:
NCT02451293
Status:
COMPLETED
Last Update Posted:
2019-01-15
First Post:
2015-05-12
Is NOT Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
The Effect of MElatonin on Depression, Anxiety, CIrcadian and Sleep Disturbances in Patients After Acute Myocardial Syndrome
Sponsor:
Zealand University Hospital
Organization:
Study Overview
Official Title:
The Effect of MElatonin on Depression, Anxiety, CIrcadian and Sleep Disturbances in Patients After Acute Myocardial Syndrome
Status:
COMPLETED
Status Verified Date:
2019-01
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
MEDACIS
Brief Summary:
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.
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.
Detailed Description:
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:
1. Melatonin will due to its antidepressant effect prevent or reduce the incidence of depressive symptoms in patients after an ACS.
2. Melatonin will due its anxiolytic effect prevent or reduce the incidence of anxiety in patients after an ACS.
3. 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.
Depression in itself requires treatment because depression after myocardial infarction is associated with reduced quality of life, reduced compliance with medication, reduced participation in cardiac rehabilitation, and less likelihood of occupational activity.
Medical treatment of depression would traditionally be a selective serotonin reuptake inhibitor (SSRI) as first-line treatment. SSRI are associated with side-effects such as sleep disorders, sexual disorders and heart rhythm disturbances.
As an alternative to SSRIs, the investigators focus on the endogenous hormone melatonin which is virtually side-effect free. Previous experiments have shown that 1000 mg of melatonin daily for one month was only associated with mild drowsiness increased. Melatonin regulates the body's circadian rhythm and plays an important role as a hypnotic and in stabilizing the sleep during the night. Sleep disorders are an integral part of the pathogenesis of depression and is important for the development of depression.
Method The investigators will perform a double-blind, placebo-controlled, randomized trial in which patients allocated to either melatonin or placebo in a prophylactic setup. Participants will be followed for 12 weeks, where they have three clinical visits and depression measurements every two weeks.
Depression in the study is measured by Major Depression Inventory (MDI), a self-rating form with 12 questions. The questionnaire is well studied and validated in a Danish population. The questions covers the 10 ICD-10 symptoms of depression, and is recommended for use in general practice. MDI is a flexible tool that can be used as a diagnostic tool and at the same time as measuring instrument for severity of depressive disorder. MDI will be administered during clinic visits and used in the outpatient phase, so the patients are followed continuously every two weeks throughout the study. Should there be a treatment demanding depression (moderate/severe) the participant will be referred to a dedicated psychiatrist who will perform a Hamilton evaluation and make treatment recommendations.
Participants are also assessed for depression and anxiety by using the Hospital anxiety and depression scale (HADS). A large Danish study of patients after myocardial infarction was shown have a prevalence of depression in 20%, and HADS will also be used to compare included with non-participating patients (external validity).
Melatonin has been shown ameliorative effect on sleep and circadian rhythm. Sleep and circadian rhythm disorders are an integral part of the development and maintenance of depression. These will be monitored intensively with actigraphy (objective sleep measurements), Pittsburgh sleep quality index (PSQI), sleep diaries and visual analog scales from inclusion meeting to first clinical control. Afterwards subjective sleep measurements will be performed every two weeks.
Sample size is calculated on the basis of a conservative assumption that, 31 % of patients following ACS will develop depressive symptoms, which the investigators assume can be reduced to 15.5 % by Melatonin treatment. Power calculation is based on two-sided test, and with a power of 0.80 and the significance level 5 % (alfa= 0.05), the required sample size in each group is 116. There are no interim efficacy analyses planned. The study will proceed until 120 patients have been enrolled in each arm.
MEFACS subtrial (single center)
The objective of the MEFACS study is to investigate whether prophylactic treatment with melatonin has an effect on endothelial dysfunction. Secondarily, our objective is to investigate the effect of melatonin on inflammation markers.
The MEFACS trial is a sub-trial of the MEDACIS trial, and The MEFACS trial will be carried out as a single center trial on a subpopulation of the patients enrolled in the MEDACIS trial.
The MEFACS trial will include 2 x 15 patients.
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:
1. Melatonin will due to its antidepressant effect prevent or reduce the incidence of depressive symptoms in patients after an ACS.
2. Melatonin will due its anxiolytic effect prevent or reduce the incidence of anxiety in patients after an ACS.
3. 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.
Depression in itself requires treatment because depression after myocardial infarction is associated with reduced quality of life, reduced compliance with medication, reduced participation in cardiac rehabilitation, and less likelihood of occupational activity.
Medical treatment of depression would traditionally be a selective serotonin reuptake inhibitor (SSRI) as first-line treatment. SSRI are associated with side-effects such as sleep disorders, sexual disorders and heart rhythm disturbances.
As an alternative to SSRIs, the investigators focus on the endogenous hormone melatonin which is virtually side-effect free. Previous experiments have shown that 1000 mg of melatonin daily for one month was only associated with mild drowsiness increased. Melatonin regulates the body's circadian rhythm and plays an important role as a hypnotic and in stabilizing the sleep during the night. Sleep disorders are an integral part of the pathogenesis of depression and is important for the development of depression.
Method The investigators will perform a double-blind, placebo-controlled, randomized trial in which patients allocated to either melatonin or placebo in a prophylactic setup. Participants will be followed for 12 weeks, where they have three clinical visits and depression measurements every two weeks.
Depression in the study is measured by Major Depression Inventory (MDI), a self-rating form with 12 questions. The questionnaire is well studied and validated in a Danish population. The questions covers the 10 ICD-10 symptoms of depression, and is recommended for use in general practice. MDI is a flexible tool that can be used as a diagnostic tool and at the same time as measuring instrument for severity of depressive disorder. MDI will be administered during clinic visits and used in the outpatient phase, so the patients are followed continuously every two weeks throughout the study. Should there be a treatment demanding depression (moderate/severe) the participant will be referred to a dedicated psychiatrist who will perform a Hamilton evaluation and make treatment recommendations.
Participants are also assessed for depression and anxiety by using the Hospital anxiety and depression scale (HADS). A large Danish study of patients after myocardial infarction was shown have a prevalence of depression in 20%, and HADS will also be used to compare included with non-participating patients (external validity).
Melatonin has been shown ameliorative effect on sleep and circadian rhythm. Sleep and circadian rhythm disorders are an integral part of the development and maintenance of depression. These will be monitored intensively with actigraphy (objective sleep measurements), Pittsburgh sleep quality index (PSQI), sleep diaries and visual analog scales from inclusion meeting to first clinical control. Afterwards subjective sleep measurements will be performed every two weeks.
Sample size is calculated on the basis of a conservative assumption that, 31 % of patients following ACS will develop depressive symptoms, which the investigators assume can be reduced to 15.5 % by Melatonin treatment. Power calculation is based on two-sided test, and with a power of 0.80 and the significance level 5 % (alfa= 0.05), the required sample size in each group is 116. There are no interim efficacy analyses planned. The study will proceed until 120 patients have been enrolled in each arm.
MEFACS subtrial (single center)
The objective of the MEFACS study is to investigate whether prophylactic treatment with melatonin has an effect on endothelial dysfunction. Secondarily, our objective is to investigate the effect of melatonin on inflammation markers.
The MEFACS trial is a sub-trial of the MEDACIS trial, and The MEFACS trial will be carried out as a single center trial on a subpopulation of the patients enrolled in the MEDACIS trial.
The MEFACS trial will include 2 x 15 patients.
Study Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
Secondary ID Infos
| Secondary ID | Type | Domain | Link | View |
|---|---|---|---|---|
| 2015-002116-32 | EUDRACT_NUMBER | None | View |