The Effect of MElatonin on Depression, Anxiety, CIrcadian and Sleep Disturbances in Patients After Acute Myocardial Syndrome (MEDACIS)
![]() |
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. |
ClinicalTrials.gov Identifier: NCT02451293 |
Recruitment Status :
Completed
First Posted : May 21, 2015
Last Update Posted : January 15, 2019
|
- Study Details
- Tabular View
- No Results Posted
- Disclaimer
- How to Read a Study Record
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.
Condition or disease | Intervention/treatment | Phase |
---|---|---|
Depression Acute Coronary Syndrome | Drug: Melatonin (N-acetyl-5-methoxytryptamine) Drug: Placebo | Phase 2 Phase 3 |

Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 252 participants |
Allocation: | Randomized |
Intervention Model: | Parallel Assignment |
Masking: | Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) |
Primary Purpose: | Treatment |
Official Title: | The Effect of MElatonin on Depression, Anxiety, CIrcadian and Sleep Disturbances in Patients After Acute Myocardial Syndrome |
Actual Study Start Date : | January 18, 2016 |
Actual Primary Completion Date : | August 18, 2017 |
Actual Study Completion Date : | July 20, 2018 |

Arm | Intervention/treatment |
---|---|
Active Comparator: Melatonin (N-acetyl-5-methoxytryptamine)
Melatonin (N-acetyl-5-methoxytryptamine) 25 mg oral administration 1 hour before bedtime for 12 weeks.
|
Drug: Melatonin (N-acetyl-5-methoxytryptamine) |
Placebo Comparator: Placebo
Comparable placebo pill, oral administration 1 hour before bedtime for 12 weeks.
|
Drug: Placebo |
- Major Depression Inventory (MDI) [ Time Frame: Depression at one point in the study (not including baseline) out of 6 measurements at app. day 14. ]MDI is a self-rating depression scale with 12 questions. MDI has previously been investigated in a Danish population. On a six-point Likert scale, the items measure how much time the symptoms have been present during the last 14 days. MDI is scored according to specific guidelines and can be used either as a rating scale or diagnostic instrument. For inclusion the investigators used the diagnostic instrument (depression was an exclusion criteria) and for all other MDI measurements the investigators used the rating scale. Diagnostic scale using the ICD-10 algorithm: Mild depression: 2 core symptoms and 2 other symptoms Moderate depression: 2 core symptoms and 4 other symptoms Severe depression: 3 core symptoms and 5 other symptoms 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
- Major Depression Inventory (MDI) [ Time Frame: Depression at one point in the study (not including baseline) out of 6 measurements at app. day 28 ]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.
- Major Depression Inventory (MDI) [ Time Frame: Depression at one point in the study (not including baseline) out of 6 measurements at app. day 42 ]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.
- Major Depression Inventory (MDI) [ Time Frame: Depression at one point in the study (not including baseline) out of 6 measurements at app. day 56 ]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.
- Major Depression Inventory (MDI) [ Time Frame: Depression at one point in the study (not including baseline) out of 6 measurements at app. day 70 ]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.
- Major Depression Inventory (MDI) [ Time Frame: 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.
- Actigraphy - Sleep outcomes - Time in bed [ Time Frame: From inclusion to first clinical visit (app. 14 days) ]Outcomes measured - Nightime: time in bed, (min)
- Actigraphy - Sleep outcomes - total sleep time [ Time Frame: From inclusion to first clinical visit (app. 14 days) ]Outcomes measured - Nightime: total sleep time (min)
- Actigraphy - Sleep outcomes - sleep effetiveness [ Time Frame: From inclusion to first clinical visit (app. 14 days) ]Outcomes measured - Nightime: sleep effectiveness (%)
- Actigraphy - Sleep outcomes - wake after sleep onset [ Time Frame: From inclusion to first clinical visit (app. 14 days) ]Outcomes measured - Nightime: wake after sleep onset (min)
- Actigraphy - Sleep outcomes - sleep latency [ Time Frame: From inclusion to first clinical visit (app. 14 days) ]Outcomes measured - Nightime: sleep latency (min)
- Actigraphy - Sleep outcomes - number of awakenings [ Time Frame: From inclusion to first clinical visit (app. 14 days) ]Outcomes measured - Nightime: number of awakenings (duration of 5 min).
- Actigraphy - Sleep outcomes - time awake [ Time Frame: From inclusion to first clinical visit (app. 14 days) ]Outcomes measured - Daytime: Time awake (min)
- Actigraphy - Sleep outcomes - time asleep [ Time Frame: From inclusion to first clinical visit (app. 14 days) ]Outcomes measured - Daytime: time asleep (min)
- Actigraphy - Sleep outcomes - number of naps [ Time Frame: From inclusion to first clinical visit (app. 14 days) ]Outcomes measured - Daytime: number of naps
- Actigraphy - circadian outcomes - Mesor [ Time Frame: From inclusion to first clinical visit (app. 14 days) ]Outcomes measured: Mesor - Adjusted mean of activity counts over 24 hours.
- Actigraphy - circadian outcomes - Acrophase [ Time Frame: From inclusion to first clinical visit (app. 14 days) ]Outcomes measured: Acrophase - Time of peak amplitude.
- Actigraphy - circadian outcomes - Amplitude [ Time Frame: From inclusion to first clinical visit (app. 14 days) ]Outcomes measured: Amplitude - Peak activity value above mesor.
- Actigraphy - circadian outcomes - F-statistics [ Time Frame: From inclusion to first clinical visit (app. 14 days) ]Outcomes measured: F-statistics - Goodness of fit of general cosine model in summarizing the actual data.
- Actigraphy - circadian outcomes - Inter-daily stability [ Time Frame: From inclusion to first clinical visit (app. 14 days) ]Outcomes measured: Inter-daily Stability - The regularity of the rhythm from one day to next.
- Actigraphy - circadian outcomes - Inter-daily variability [ Time Frame: From inclusion to first clinical visit (app. 14 days) ]Outcomes measured: Intra-daily Variability - Fragmentation of the rhythm.
- Anxiety measured by Hospital anxiety and depression scale (HADS-A) [ Time Frame: Anxiety at one point in the study (not including baseline) out of 2 measurements at app. day 14 and day 84 of the study ]The HADS consists two subscales; one for anxiety (HADS-A) and one for depression (HADS-D), which can be used separately. Each scale consists of 7 questions which are graded on a 4 point scale (0-1-2-3) and is summed into a total score between 0-21. A score of 7 or lower is negative case, a score of 8 - 10 is a doubtful case, and a score of 11 or above is a positive case. The scale inquires about the presence of symptoms during the last week and, hence, should be administered at a maximum of weekly intervals].
- Depression measured by Hospital anxiety and depression scale (HADS-D) [ Time Frame: Depression at one point in the study (not including baseline) out of 2 measurements at app. day 14 and day 84 of the study ]The HADS consists two subscales; one for anxiety (HADS-A) and one for depression (HADS-D), which can be used separately. Each scale consists of 7 questions which are graded on a 4 point scale (0-1-2-3) and is summed into a total score between 0-21. A score of 7 or lower is negative case, a score of 8 - 10 is a doubtful case, and a score of 11 or above is a positive case. The scale inquires about the presence of symptoms during the last week and, hence, should be administered at a maximum of weekly intervals].
- Subjective sleep quality measured by Pittsburgh sleep quality index (PSQI) [ Time Frame: 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 ]The PSQI, which asses sleep quality during the last 4 weeks, and has a clinical established cut of 5 ≥ as poor sleeper and 8≥ as having sleep problems needing treatment
- Sleep diary [ Time Frame: 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. ]A sleep diary is the patient's own account of sleep data, and they are asked to fill in a diary page each morning after awakening.
- UKU side effect rating scale [ Time Frame: 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 ]The UKU has been develop for use to monitor side effect of psychotropic drugs, and has been validated in several Nordic countries. The UKU consists of a single symptom rating scale (48 items), a global assessment of influence of side effect on patients daily lives (patient and doctor), and the side effect influence on continued medication treatment.
- VAS Data on Anxiety [ Time Frame: 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. ]Anxiety measured by VAS (visual analog scale). A subjective feeling of anxiety was registered on a VAS going from "no anxiety", equivalent to 0mm to "worst possible anxiety", equivalent to 100mm.
- VAS Data on Fatigue [ Time Frame: 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. ]Fatigue measured by VAS (visual analog scale). A subjective feeling of Fatigue was registered on a VAS going from "no Fatigue", equivalent to 0 mm to "worst possible Fatigue", equivalent to 100mm.
- VAS Data on Pain [ Time Frame: 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. ]Pain measured by VAS (visual analog scale). A subjective feeling of Pain was registered on a VAS going from "no Pain", equivalent to 0 mm to "worst possible Pain", equivalent to 100mm.
- VAS Data on Sleep Quality [ Time Frame: 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. ]Sleep Quality measured by VAS (visual analog scale). A subjective feeling of Sleep Quality was registered on a VAS going from "best possible sleep", equivalent to 0 mm to "worst possible sleep", equivalent to 100mm.
- VAS Data on General Well-being [ Time Frame: 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. ]General Well-being measured by VAS (visual analog scale). A subjective feeling of General Well-being was registered on a VAS going from "very high well-being", equivalent to 0 mm to "very low well-being", equivalent to 100mm.
- Endothelial function (EndoPAT) [ Time Frame: From inclusion (day 0), first clinical visit (day 14), and final visit (day 84). ]Endothelial function measured by EndoPAT with an outcome measure of reactive hyperemia index (RHI).
- Blood sample [ Time Frame: Blood sample will be drawn at day 0 and at day 84. ]The blood will be stored in a biobank for later analysis. A not yet determined panel of MiRNA will be measured.
- Oxidative-stress markers [ Time Frame: Blood sample will be drawn at day 0 and at day 84 ]Blood work, oxidative-stress markers ADMA and Arginine.

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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).

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02451293
Denmark | |
Roskilde and Køge Hospital, Department of Surgery. | |
Køge, Danmark, Denmark, 4600 | |
Department of internal Medicin, Holbaek Sygehus | |
Holbæk, Zealand, Denmark, 4300 | |
Department of Cardiology, Roskilde Sygehus | |
Roskilde, Zealand, Denmark, 4000 | |
Department of internal medicin, M5 | |
Køge, Zeland, Denmark, 4600 | |
Department of Cardiology, Hvidovre Hospital, | |
Hvidovre, Denmark, 2650 | |
Department of Cardiology, Slagelse Sygehus | |
Slagelse, Denmark, 4200 |
Principal Investigator: | Michael Tvilling Madsen, M.D. | Department of surgery. Koege and Roskilde Hospital | |
Study Chair: | Ismail Gögenur, M.D. Professor | Department of surgery. Koege and Roskilde Hospital | |
Study Chair: | Erik Simonsen, M.D. Professor | Psychiatric Research Unit, Region Zealand |
Responsible Party: | Zealand University Hospital |
ClinicalTrials.gov Identifier: | NCT02451293 |
Other Study ID Numbers: |
MTM-03 2015-002116-32 ( EudraCT Number ) |
First Posted: | May 21, 2015 Key Record Dates |
Last Update Posted: | January 15, 2019 |
Last Verified: | January 2019 |
Depression Acute Coronary Syndrome Anxiety Sleep Circadian |
Dyssomnias Parasomnias Acute Coronary Syndrome Syndrome Depression Depressive Disorder Disease Pathologic Processes Behavioral Symptoms Mood Disorders Mental Disorders Myocardial Ischemia |
Heart Diseases Cardiovascular Diseases Vascular Diseases Sleep Wake Disorders Nervous System Diseases Melatonin Antioxidants Molecular Mechanisms of Pharmacological Action Protective Agents Physiological Effects of Drugs Central Nervous System Depressants |