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Trial record 1 of 1 for:    MEDACIS
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The Effect of MElatonin on Depression, Anxiety, CIrcadian and Sleep Disturbances in Patients After Acute Myocardial Syndrome (MEDACIS)

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ClinicalTrials.gov Identifier: NCT02451293
Recruitment Status : Completed
First Posted : May 21, 2015
Last Update Posted : January 15, 2019
Sponsor:
Collaborators:
Psychiatric Research Unit, Region Zealand, Denmark
University of Copenhagen
Pharma Nord
Information provided by (Responsible Party):
Zealand University Hospital

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.


Condition or disease Intervention/treatment Phase
Depression Acute Coronary Syndrome Drug: Melatonin (N-acetyl-5-methoxytryptamine) Drug: Placebo Phase 2 Phase 3

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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

Resource links provided by the National Library of Medicine


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



Primary Outcome Measures :
  1. 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

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.


Secondary Outcome Measures :
  1. Actigraphy - Sleep outcomes - Time in bed [ Time Frame: From inclusion to first clinical visit (app. 14 days) ]
    Outcomes measured - Nightime: time in bed, (min)

  2. Actigraphy - Sleep outcomes - total sleep time [ Time Frame: From inclusion to first clinical visit (app. 14 days) ]
    Outcomes measured - Nightime: total sleep time (min)

  3. Actigraphy - Sleep outcomes - sleep effetiveness [ Time Frame: From inclusion to first clinical visit (app. 14 days) ]
    Outcomes measured - Nightime: sleep effectiveness (%)

  4. 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)

  5. Actigraphy - Sleep outcomes - sleep latency [ Time Frame: From inclusion to first clinical visit (app. 14 days) ]
    Outcomes measured - Nightime: sleep latency (min)

  6. 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).

  7. Actigraphy - Sleep outcomes - time awake [ Time Frame: From inclusion to first clinical visit (app. 14 days) ]
    Outcomes measured - Daytime: Time awake (min)

  8. Actigraphy - Sleep outcomes - time asleep [ Time Frame: From inclusion to first clinical visit (app. 14 days) ]
    Outcomes measured - Daytime: time asleep (min)

  9. Actigraphy - Sleep outcomes - number of naps [ Time Frame: From inclusion to first clinical visit (app. 14 days) ]
    Outcomes measured - Daytime: number of naps

  10. 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.

  11. Actigraphy - circadian outcomes - Acrophase [ Time Frame: From inclusion to first clinical visit (app. 14 days) ]
    Outcomes measured: Acrophase - Time of peak amplitude.

  12. Actigraphy - circadian outcomes - Amplitude [ Time Frame: From inclusion to first clinical visit (app. 14 days) ]
    Outcomes measured: Amplitude - Peak activity value above mesor.

  13. 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.

  14. 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.

  15. 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.

  16. 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].

  17. 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].

  18. 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

  19. 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.

  20. 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.

  21. 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.

  22. 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.

  23. 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.

  24. 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.

  25. 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.

  26. 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).


Other Outcome Measures:
  1. 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.

  2. 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.



Information from the National Library of Medicine

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.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. 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.
  2. Participants should be 18 years or older.
  3. No sign of depression on Major Depression Inventory (MDI) at the point of enrolment.
  4. Participants must sign an informed consent form
  5. Females not in menopause (defined as no menstruation during the last 12 months) should have a negative pregnancy test.

Exclusion Criteria:

  1. Known allergic reaction to melatonin.
  2. Ongoing or previous pharmacological treated depression or bipolar disorder.
  3. No dementia as determined by mini mental state examination score (MMSE) < 24
  4. At the point of inclusion no participation in another pharmacological intervention trial is allowed.
  5. No diagnose of Rotor or Dubin-Johnson syndrome, epilepsy, sleep apnoea syndrome, systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) or multiple sclerosis is allowed.
  6. Severe liver disease defined as transaminases above X 3 normal levels, and severe kidney disease defined as eGRF under 40 ml/min.
  7. Ongoing hypnotic treatment.
  8. Known sleep disorder (e.g. insomnia, restless legs etc.)
  9. Work involving nightshifts.
  10. Daily alcohol consumption above 5 units of alcohol (1 unit = 12 g alcohol)
  11. Predictable poor compliance ( e.g. not speaking fluent Danish)
  12. Pregnant or breastfeeding.
  13. Severe, life-threatening medical condition, that implies that the patient cannot participate in a the study course. (e.g. cancer, stroke, )
  14. Indication for coronary artery bypass graft (CABG).

    For the MEFACS subtrial - (single center)

  15. 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).

Information from the National Library of Medicine

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


Locations
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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
Sponsors and Collaborators
Zealand University Hospital
Psychiatric Research Unit, Region Zealand, Denmark
University of Copenhagen
Pharma Nord
Investigators
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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

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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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
Keywords provided by Zealand University Hospital:
Depression
Acute Coronary Syndrome
Anxiety
Sleep
Circadian
Additional relevant MeSH terms:
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Dyssomnias
Sleep Wake Disorders
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
Nervous System Diseases
Neurologic Manifestations
Signs and Symptoms
Melatonin
Antioxidants
Molecular Mechanisms of Pharmacological Action
Protective Agents
Physiological Effects of Drugs
Central Nervous System Depressants