Clinical Trial Results:
Multicenter, randomized, double-blind, placebo controlled trial of 2 mg melatonin for circadian phase adjustment and improvement of metabolic control in night shift workers
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Summary
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EudraCT number |
2012-005254-30 |
Trial protocol |
DE |
Global end of trial date |
07 Mar 2017
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Results information
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Results version number |
v1(current) |
This version publication date |
07 Sep 2022
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First version publication date |
07 Sep 2022
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
EuRhythDiaII
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT02108353 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
University Medical Center Hamburg-Eppendorf (UKE)
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Sponsor organisation address |
Martinistrasse 52, Hamburg, Germany,
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Public contact |
Prof. Dr. Rainer Boeger
, Department of Clinical Pharmacology and Toxicoloy
University Medical Center Hamburg-Eppendorf, +49 40741059759, boeger@uke.de
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Scientific contact |
Prof. Dr. Rainer Boeger
, Department of Clinical Pharmacology and Toxicoloy
University Medical Center Hamburg-Eppendorf, +49 40741059759, boeger@uke.de
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
31 May 2018
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
18 Sep 2014
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Global end of trial reached? |
Yes
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Global end of trial date |
07 Mar 2017
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Was the trial ended prematurely? |
No
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General information about the trial
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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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Protection of trial subjects |
Measures were taken to minimize invasive sampling for all subjects. Patient visits were coordinate study requirements with the working schedules to reduce conflicts with daily working life.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
01 Jan 2014
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Germany: 36
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Worldwide total number of subjects |
36
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EEA total number of subjects |
36
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
36
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
Individuals were eligible if they were night shift workers on regular night shifts with at least four night shifts per month; if they had been on regular night shifts for at least six months before inclusion into the study; if they were above the age of 18 inclusive. | |||||||||||||||
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Pre-assignment
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Screening details |
Individuals were excluded if they were pregnant or breast-fedding, had a history of physical or psychiatric illness , known autoimmune disease, evidence of relevant renal insufficiency (GFR < 60 mL/min), liver injury (AST, ALT, GGT, Ap, or bilirubin elevated), intolerance to study products, galactose intolerance, or used melatonin before. | |||||||||||||||
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Period 1
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Period 1 title |
intervention phase
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Is this the baseline period? |
Yes | |||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | |||||||||||||||
Roles blinded |
Subject, Investigator, Monitor, Data analyst, Assessor | |||||||||||||||
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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melatonin | |||||||||||||||
Arm description |
Melatonin sustained release 2 mg tablets (Circadin) once daily 0.5-1 hour before going to bed | |||||||||||||||
Arm type |
Experimental | |||||||||||||||
Investigational medicinal product name |
Circadin 2 mg tablets
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
One table once daily 0.5-1 hour before going to bed.
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Arm title
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Placebo | |||||||||||||||
Arm description |
One tablet of placebo per day 0.5-1 hour before going to bed | |||||||||||||||
Arm type |
Placebo | |||||||||||||||
Investigational medicinal product name |
Placebo
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
one tablet once daily 0.5-1 hour before going to bed
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Period 2
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Period 2 title |
Wash-out period
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Is this the baseline period? |
No | |||||||||||||||
Allocation method |
Non-randomised - controlled
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Blinding used |
Double blind | |||||||||||||||
Roles blinded |
Subject, Investigator, Monitor, Data analyst, Assessor | |||||||||||||||
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Arms
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Arm title
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No active treatment | |||||||||||||||
Arm description |
All study poarticipants, both ffrom the melatonin and placebo groups during the inervention phase, were allocated to "No active treatment" in the second half of the study. | |||||||||||||||
Arm type |
No intervention | |||||||||||||||
Investigational medicinal product name |
No investigational medicinal product assigned in this arm
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Baseline characteristics reporting groups
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Reporting group title |
melatonin
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Reporting group description |
Melatonin sustained release 2 mg tablets (Circadin) once daily 0.5-1 hour before going to bed | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo
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Reporting group description |
One tablet of placebo per day 0.5-1 hour before going to bed | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
melatonin
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Reporting group description |
Melatonin sustained release 2 mg tablets (Circadin) once daily 0.5-1 hour before going to bed | ||
Reporting group title |
Placebo
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Reporting group description |
One tablet of placebo per day 0.5-1 hour before going to bed | ||
Reporting group title |
No active treatment
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Reporting group description |
All study poarticipants, both ffrom the melatonin and placebo groups during the inervention phase, were allocated to "No active treatment" in the second half of the study. | ||
Subject analysis set title |
primary endpoint
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Subject analysis set type |
Per protocol | ||
Subject analysis set description |
All subjects that completed at least visits 1 (baseline) and 2 (after 12 weeks of intervention).
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End point title |
serum glucose during OGTT | ||||||||||||||||||||
End point description |
AUC of the serum glucose over time during OGTT (0-120 min)
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End point type |
Primary
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End point timeframe |
baseline, 12 weeks, 24 weeks
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Attachments |
AUC of serum glucose |
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Statistical analysis title |
One-way ANOVA | ||||||||||||||||||||
Comparison groups |
melatonin v Placebo v No active treatment v primary endpoint
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Number of subjects included in analysis |
71
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||||||||||
P-value |
< 0.05 | ||||||||||||||||||||
Method |
ANOVA | ||||||||||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||||||||||
Confidence interval |
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Variability estimate |
Standard deviation
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Adverse events information
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Timeframe for reporting adverse events |
24 weeks (12 weeks of double-blind intervention, followed by 12 weeks of wash-out)
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Assessment type |
Systematic | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
15.0
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Reporting groups
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Reporting group title |
melatonin
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Reporting group description |
Melatonin sustained release 2 mg tablets (Circadin) once daily 0.5-1 hour before going to bed | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo
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Reporting group description |
One tablet of placebo per day 0.5-1 hour before going to bed | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 1% | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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14 Nov 2013 |
Inclusion Criteria.: Number of required night shifts was changed to 4 and “Signed and written in-formed consent” was added. “Pregnancy and breast feeding” was changed in “Pregnancy or breast feeding” as Exclusion Criteria.
72 h blood glucose monitoring” was deleted from the protocol.
Total blood amount was adapted.
Urine pregnancy test for female subjects was added to the Screening as well as to every ambulato-ry visit.
Intrauterine devices were specified without hormonal component and and oral contraceptives were deleted as Concomitant Therapy.
The study visit schedule was changed in 3-7 days after the end of the night shift and the in-patient-period was set at 26 hours.
24 h Actigraphy Measurement was prolonged to 72 h.
Screening and follow-up were deleted from vital signs.
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22 Jul 2014 |
Inclusion Criteria: “Evidence of impaired fasting glucose or impaired glucose tolerance at screening (applicable for 50% of the participants).” was deleted.
The treatment administration for consecutive night shifts was defined.
The determination of FSH levels in female subjects >50 years was deleted, thus an urine pregnancy test to exclude pregnancy is performed in all female subjects.
New clinically significant abnormal findings, which occur after the first dosing are captured as AE.
An acceptable form of contraception as requirement for all sexually-active females of child-bearing and non-child bearing potential was added. |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| The anticipated number of study subjects was not reached. | |||
