E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Depression Anxiety Sleep disturbances Circadian disturbances |
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E.1.1.1 | Medical condition in easily understood language |
Acute Coronary Syndrome - ST elevation myocardial infarction, non ST elevation myocardial infarction, or unstable angina . |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cardiovascular Diseases [C14] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10009190 |
E.1.2 | Term | Circadian dysrhythmia |
E.1.2 | System Organ Class | 100000004852 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10002865 |
E.1.2 | Term | Anxiety reaction |
E.1.2 | System Organ Class | 100000004873 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10040999 |
E.1.2 | Term | Sleep disturbed |
E.1.2 | System Organ Class | 100000004873 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10012402 |
E.1.2 | Term | Depressive episode |
E.1.2 | System Organ Class | 100000004873 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The objective of the study is to investigate whether prophylactic treatment with melatonin has an effect on depressive symptoms. |
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E.2.2 | Secondary objectives of the trial |
Secondary objective of the study is to investigate melatonin’s effect on anxiety, sleep and circadian disturbances.
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Title: The effect of Melatonin on Endothelial Function in patients after acute coronary syndrome - MEFACS - trial Date: 29.09.16 Version: Main protokol version 4 (MTM-04) - Single center sub-study.
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.
Effect parameter: Primary: Endothelial function measured by EndoPAT with an outcome measure of reactive hyperemia index (RHI). Secondary: Blood work, oxidative-stress markers ADMA and Arginine.
Additional exclusion criteria: 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).
Outcome Assesment: EndoPAT - day 0, 14 and 84. Bloodwoork - day 0 and 84
Sample size: 2 x 15 patients.
The MEFACS trial will be conducted at the Department of Cardiology, University of Copenhagen, Zealand University Hospital, Køge, Denmark.
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E.3 | Principal 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. Furthermore, reproductive females should use a secure birth control (intrauterine devices, hormonal contraceptives including – oral pills, patches, vaginal rings and injections) during the entire period of the trial. |
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E.4 | Principal 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 (appendix 2) 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 (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). |
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary effect parameter • MDI (Major Depression Inventory)
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Primary Outcome Measure: Major Depression Inventory (MDI) Time Frame: Depression at one point in the study (not including baseline) out of 6 measurements at app. day 14, 28, 42, 56, 70 and 84. MDI is a self-rating depression scale with 12 questions. 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 |
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E.5.2 | Secondary end point(s) |
Secondary effect parameter • Anxiety measured by Hospital anxiety and depression scale (HADS-A) • Depression measured by Hospital anxiety and depression scale (HADS-D) • Sleep and circadian outcomes measured by actigraphy. • Subjective sleep quality measured by Pittsburgh sleep quality index (PSQI) • Safety, Side-effect and compliance to study medication (UKU sideeffect scale). • Sleep diary • Sleep, pain, anxiety, fatigue, and general well-being measured by VAS. • Blood work – Samples will be collected and stored in a bio-bank for later analysis.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
HADS-A: Day 0, 14 and 84 HADS-D: Day 0, 14 and 84 Sleep and circadian outcomes measured by actigraphy: Day 0-14. Subjective sleep quality measured by Pittsburgh sleep quality index (PSQI): Day 0, 14 and 84. Safety and Side-effect (UKU sideeffect scale): Day 14, 28, 42, 56, 70 and 84. Compliance to study medication: Day 14 and 84. Sleep diary: Day 0-14, 28, 42, 56, 70 and 84. Sleep, pain, anxiety, fatigue, and general well-being measured by VAS: : Day 0-14, 28, 42, 56, 70 and 84. Blood samples: Day 0 and 84. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | Yes |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The end of the trial is the follow-up/final visit, 12 weeks after inclusion, for the last patient included in the trial. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |