E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Insomnia because of disturbed sleep-work-rhythm |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nutritional and Metabolic Diseases [C18] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10032168 |
E.1.2 | Term | Other insomnia |
E.1.2 | System Organ Class | 10037175 - Psychiatric disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10022443 |
E.1.2 | Term | Insomnia related to another mental condition |
E.1.2 | System Organ Class | 10037175 - Psychiatric disorders |
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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 |
To investigate in night shift workers the efficacy of melatonin over 12 weeks to a) improve metabolic control and b) regulate expression patterns of genes involved in the regulation of metabolism and circadian rhythm |
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E.2.2 | Secondary objectives of the trial |
To provide data on the interaction between genes, epigenetics, metabolism, cardiovascular function and the internal clock in order to identify novel biomarkers and genes of interest for future therapeutic approaches in targeting circadian rhythms of metabolic control. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1.Ability to understand and personally sign and date the in-formed consent to participate in the study before completing any study related procedures.
2.White male and female above the age of 18 years inclusive at the time of consent.
3.Night shift workers on regular night shifts with at least 4 night shifts per month during the study period. Subjects must have been on regular night shifts for at least 6 months before inclusion into the study.
4.The subject is co-operative and available for the entire study.
5. Signed and written informed consent.
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E.4 | Principal exclusion criteria |
1.Pregnancy or breast feeding.
2.Current or relevant history of physical or psychiatric illness that makes the subject unlikely to fully complete the study, or any condition that presents undue risk from the study procedures.
3.Known autoimmune disease.
4.Evidence of relevant renal insufficiency as indicated by an estimated glomerular filtration rate below 60 ml/min.
5.Clinical evidence of liver disease or liver injury as indicated by abnormal liver function tests such as ALT, AST, GGT, alkaline phosphatase, or serum bilirubin.
6.Known or suspected intolerance or hypersensitivity to the study medication, closely related compounds, or any of the stated ingredients.
7.Current or history of hereditary galactose-intolerance, lapp-lactose-deficiency or glucose-galactose-malabsorption.
8.Use of melatonin, fluvoxamine, cimetidine, quinolones, car-bamazepine, rifampicine, 5-methoxypsoralene or 8-methoxypsoralene within 4 weeks prior to the inclusion into the study.
9.Long distance travel over more than 3 time zones within 4 weeks prior to study inclusion.
10.Subjects who consume more than 750 mg per day caffeine.
11.Donation of blood or blood products (e.g., 450 mL or more of plasma or platelets) within 60 days prior to inclusion into the study.
12.Inability or difficulties to swallow all investigational medicinal products.
13.Participation in a clinical investigation within the past 4 weeks before first administration of IMP.
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E.5 End points |
E.5.1 | Primary end point(s) |
The change in the area under the curve (AUC) of blood glucose during an oral glucose tolerance test between baseline and 12 weeks of intervention within groups. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
•The change in the area under the curve (AUC) of blood glu-cose during an oral glucose tolerance test between week 12 and week 24 (= after 12 weeks without intervention).
•The change in the area under the curve (AUC) of blood insu-lin during an oral glucose tolerance test between baseline and 12 weeks of intervention.
•The change in the area under the curve (AUC) of blood insu-lin during an oral glucose tolerance test between week 12 and week 24 (= after 12 weeks without intervention).
•The change in indices of glucose homeostasis (HOMA, QUICKI index, Stumvoll-ISI index, HbA1c) between baseline and 12 weeks of intervention.
•The difference in the above-mentioned parameters of metabolic control between intervention and control at 12 weeks of intervention and at 24 weeks.
•The change in body weight, BMI, abdominal circumference, biomarkers and vascular function between baseline and 12 weeks of intervention and between week 12 and 24.
•The change in the gene expression patterns of Clock genes in peripheral blood monocytic cells (PBMC) between base-line and 12 weeks of intervention and between week 12 and 24.
•The differences in epigenetic profiles of genes involved in circadian rhythm between the study groups after 12 weeks of intervention and between week 12 and 24.
•The differences in plasma and serum biomarkers between baseline and 12 weeks of intervention and between week 12 and 24.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | No |
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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 4 |
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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 6 |