The Effect of MElatonin on Depression, Anxiety, CIrcadian and Sleep Disturbances in Patients After Acute Myocardial Syndrome

NCT02451293 | Completed Phase 2 DMC

• 2 other identifiers: MTM-032015-002116-32
• Study Type: interventional
• Target: 252
• Locations: 1 country
• Sites: 6

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.

Conditions

Depression; Acute Coronary Syndrome

Keywords

Depression; Acute Coronary Syndrome; Anxiety; Sleep; Circadian

Outcome Measures

Primary Outcomes (6)

• Major Depression Inventory (MDI)

  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

  Depression at one point in the study (not including baseline) out of 6 measurements at app. day 14.

• Major Depression Inventory (MDI)

  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.

  Depression at one point in the study (not including baseline) out of 6 measurements at app. day 28

• Major Depression Inventory (MDI)

  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.

  Depression at one point in the study (not including baseline) out of 6 measurements at app. day 42

• Major Depression Inventory (MDI)

  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.

  Depression at one point in the study (not including baseline) out of 6 measurements at app. day 56

• Major Depression Inventory (MDI)

  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.

  Depression at one point in the study (not including baseline) out of 6 measurements at app. day 70

• Major Depression Inventory (MDI)

  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.

  Depression at one point in the study (not including baseline) out of 6 measurements at app. day 84

Secondary Outcomes (26)

• Actigraphy - Sleep outcomes - Time in bed

  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 - 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 - sleep latency

  From inclusion to first clinical visit (app. 14 days)

Other Outcomes (2)

• Blood sample

  Blood sample will be drawn at day 0 and at day 84.

• Oxidative-stress markers

  Blood sample will be drawn at day 0 and at day 84

Study Arms (2)

Melatonin (N-acetyl-5-methoxytryptamine)

ACTIVE COMPARATOR

Melatonin (N-acetyl-5-methoxytryptamine) 25 mg oral administration 1 hour before bedtime for 12 weeks.

Drug: Melatonin (N-acetyl-5-methoxytryptamine)

Placebo

PLACEBO COMPARATOR

Comparable placebo pill, oral administration 1 hour before bedtime for 12 weeks.

Drug: Placebo

Interventions

Melatonin (N-acetyl-5-methoxytryptamine) DRUG

Melatonin (N-acetyl-5-methoxytryptamine)

Placebo DRUG

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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
• 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).

Sponsors & Collaborators

• Zealand University Hospital: lead
• Psychiatric Research Unit, Region Zealand, Denmark: collaborator
• University of Copenhagen: collaborator
• Pharma Nord: collaborator

Study Sites (6)

Roskilde and Køge Hospital, Department of Surgery.

Køge, Danmark, 4600, Denmark

Location

Department of internal Medicin, Holbaek Sygehus

Holbæk, Region Sjælland, 4300, Denmark

Location

Department of internal medicin, M5

Køge, Region Sjælland, 4600, Denmark

Location

Department of Cardiology, Roskilde Sygehus

Roskilde, Region Sjælland, 4000, Denmark

Location

Department of Cardiology, Hvidovre Hospital,

Hvidovre, 2650, Denmark

Location

Department of Cardiology, Slagelse Sygehus

Slagelse, 4200, Denmark

Location

Related Publications (3)

• Madsen MT, Juel K, Simonsen E, Gogenur I, Zwisler ADO. External validity of randomized clinical trial studying preventing depressive symptoms following acute coronary syndrome. Brain Behav. 2021 Aug;11(8):e02132. doi: 10.1002/brb3.2132. Epub 2021 Jun 17.

  PMID: 34145796 DERIVED

• Madsen BK, Zetner D, Moller AM, Rosenberg J. Melatonin for preoperative and postoperative anxiety in adults. Cochrane Database Syst Rev. 2020 Dec 8;12(12):CD009861. doi: 10.1002/14651858.CD009861.pub3.

  PMID: 33319916 DERIVED

• Madsen MT, Isbrand A, Andersen UO, Andersen LJ, Taskiran M, Simonsen E, Gogenur I. The effect of MElatonin on Depressive symptoms, Anxiety, CIrcadian and Sleep disturbances in patients after acute coronary syndrome (MEDACIS): study protocol for a randomized controlled trial. Trials. 2017 Feb 23;18(1):81. doi: 10.1186/s13063-017-1806-x.

  PMID: 28228148 DERIVED

MeSH Terms

Conditions

Depression; Acute Coronary Syndrome; Anxiety Disorders

Interventions

Melatonin

Condition Hierarchy (Ancestors)

Behavioral Symptoms; Behavior; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Mental Disorders

Intervention Hierarchy (Ancestors)

Tryptamines; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Study Officials

• Michael Tvilling Madsen, M.D.

  Department of surgery. Koege and Roskilde Hospital

  PRINCIPAL INVESTIGATOR

• Ismail Gögenur, M.D. Professor

  Department of surgery. Koege and Roskilde Hospital

  STUDY CHAIR

• Erik Simonsen, M.D. Professor

  Psychiatric Research Unit, Region Zealand

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 12, 2015
• First Posted: May 21, 2015
• Study Start: January 18, 2016
• Primary Completion: August 18, 2017
• Study Completion: July 20, 2018
• Last Updated: January 15, 2019

Record last verified: 2019-01

Locations

DK (6)