Clinical Trial Results:
Chronotherapeutic lifestyle intervention for diabetes and obesity to reset the circadian rhythm and improve cardiometabolic risk in the European population
Summary
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EudraCT number |
2012-005255-17 |
Trial protocol |
GB |
Global end of trial date |
01 Nov 2017
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Results information
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Results version number |
v1(current) |
This version publication date |
03 Jan 2020
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First version publication date |
03 Jan 2020
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Other versions |
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Summary report(s) |
Eurythdia Final Report |
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 |
ED14/11124
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
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WHO universal trial number (UTN) |
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Sponsors
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Sponsor organisation name |
University of Leeds
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Sponsor organisation address |
Worsley Building, Leeds, United Kingdom, LS2 9LN
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Public contact |
Clare Skinner, University of Leeds, 0113 3434897, c.e.skinner@leeds.ac.uk
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Scientific contact |
Clare Skinner, University of Leeds, 0113 3434897, c.e.skinner@leeds.ac.uk
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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 |
23 Nov 2016
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
23 Nov 2016
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Global end of trial reached? |
Yes
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Global end of trial date |
01 Nov 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 the effectiveness of 6 months of randomization to melatonin therapy or placebo as a chronotherapeutic intervention for individuals at high risk of development of T2DM.
This will be carried out by analysing the influence of these interventions on glucose regulation, insulin resistance, cardiometabolic function and markers of central and peripheral circadian rhythms, in particular CLOCK mRNA, in healthy first degree relatives of patients with T2DM
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Protection of trial subjects |
All information collected during the course of the trial will be kept strictly confidential.
Information will be held securely on paper and electronically at the LIGHT Laboratories, University of Leeds for the duration of the study. Data collection will be performed on paper at each individual participants visit and transcribed to electronic CRFs. The paper copies containing visit data will act as source data.
The investigators will comply with all aspects of the Data Protection Act 1998.
All data obtained in this study should be entered within 7 days of patient contact in the appropriate case report form (eCRF). The investigator should ensure the accuracy, completeness, legibility and timeliness of the data reported in the CRFs and in all required reports. Data reported on the CRF should be consistent with the source documents or the discrepancies should be explained. Paper documentation will be completed in black ink ballpoint pen. Errors must be corrected by drawing a single line through the incorrect entry and writing in the new value/ data positioned as close to the original as possible. Any change or correction to should not obscure or eliminate the original entry (“correction fluid” should not be used) and should be dated, initialled and explained (if necessary) by the person making the correction. The investigator has to date and sign off the completed paper documentation including copies of blood results and any other reports. Corrections made after the investigators review and signature of the completed CRF have to be signed and dated by the investigator. If an investigation was not performed, this needs to be indicated with “n.d.” (not done).
Prior to start and during the study, when applicable, the investigator will list on the form “Delegation of Tasks” all person to whom he/ she delegated significant trial-related duties.
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Background therapy |
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Evidence for comparator |
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Actual start date of recruitment |
01 Jul 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 |
United Kingdom: 71
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Worldwide total number of subjects |
71
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EEA total number of subjects |
71
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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) |
63
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From 65 to 84 years |
8
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85 years and over |
0
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Recruitment
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Recruitment details |
A total of 4000 patients were screened and 340 relatives of patients could be contacted. A total of 75 patients willing to participate were subsequently randomized in a 1:1 random allocation held by the Leeds Teaching Hospitals Trust pharmacy to either 6 months melatonin therapy or placebo | |||||||||||||||
Pre-assignment
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Screening details |
Inclusion Criteria: Age 18-75,Males, females of non-child bearing potential (post-menopausal or 6 weeks post-sterilisation), females of child-bearing potential,)One or more first degree relative with an established diagnosis of T2DM,Absence of clinical symptoms and signs of infection,Absence of systemic disease. | |||||||||||||||
Period 1
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Period 1 title |
Overall Trial (overall period)
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Is this the baseline period? |
Yes | |||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | |||||||||||||||
Roles blinded |
Investigator, Subject | |||||||||||||||
Blinding implementation details |
Subjects were assigned to a specified treatment according to a random list, which was generated before the beginning of the study. Labelling for the study and blinding according to randomization list will be performed at the UMC-Hamburg Hospital pharmacy; study medication will be shipped from Hamburg to the hospital pharmacy in Leeds for dispensing to study participants.
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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 Treatment | |||||||||||||||
Arm description |
- | |||||||||||||||
Arm type |
Active comparator | |||||||||||||||
Investigational medicinal product name |
Oral Melatonin
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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 |
Neurim Pharmaceuticals (Zug, Switzerland swissinfo@neurim.com) will provide 2 mg prolonged-release melatonin tablet: Circadin® 2 mg tablets. Placebo tablets have been developed to match the Circadin® 2 mg tablets in blind clinical studies. They contain the same excipients than those used in the composition of Circadin® 2 mg tablets (Ammonio Methacrylate Copolymer, Type B [Eudragit RSPO®], Calcium Hydrogen Phosphate Dihydrate, Lactose Monohydrate, Silica, Colloidal Anhydrous [Aerosil®], Talcum, Magnesium Stearate), except the ethanol used to dissolve the drug substance and spray it in the dry excipient blend for a partial wet granulation. The tablets (active/placebo) are then obtained by dry-mixing and direct compression. Since the residual ethanol has to be less than 5000 ppm in the final formulation of Circadin® 2 mg tablets, the placebo formulation without ethanol can be considered as equivalent to the Circadin® tablet formulation, except the absence of the drug substance.
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Arm title
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Placebo | |||||||||||||||
Arm description |
- | |||||||||||||||
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 |
Placebo tablets have been developed to match the Circadin® 2 mg tablets in blind clinical studies. They contain the same excipients than those used in the composition of Circadin® 2 mg tablets (Ammonio Methacrylate Copolymer, Type B [Eudragit RSPO®], Calcium Hydrogen Phosphate Dihydrate, Lactose Monohydrate, Silica, Colloidal Anhydrous [Aerosil®], Talcum, Magnesium Stearate), except the ethanol used to dissolve the drug substance and spray it in the dry excipient blend for a partial wet granulation.
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Baseline characteristics reporting groups
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Reporting group title |
Melatonin Treatment
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Reporting group description |
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Reporting group title |
Placebo
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Melatonin Treatment
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Reporting group description |
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Reporting group title |
Placebo
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Reporting group description |
- |
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End point title |
The differences in indices of glucose regulation (HbA1c, OGTT, insulin AUC) between intervention and control groups. [1] | ||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
total study duration will be 26 months, with trial recruitment anticipated to be 12 months. This would leave 14 months for end point analysis.
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Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Please see results paper which has been uploaded and contains details of the statistical analysis. |
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Attachments |
Primary and Secondary outcome tables |
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No statistical analyses for this end point |
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Adverse events information [1]
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Timeframe for reporting adverse events |
AEs will be collected for all participants and will be evaluated according to the NCRI Common Toxicity Criteria. AEs will be collected for all participants from date of randomisation until 30 days after the last dose of treatment
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Assessment type |
Systematic | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
CTCAE | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
4.0
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Reporting groups
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Reporting group title |
Melatonin Treatment
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Reporting group description |
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Reporting group title |
Placebo
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Reporting group description |
- | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Notes [1] - There are no non-serious adverse events recorded for these results. It is expected that there will be at least one non-serious adverse event reported. Justification: No Non-Serious adverts were reported as this was a healthy volunteers trial. |
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Frequency threshold for reporting non-serious adverse events: 5% | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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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06 Oct 2014 |
Protocol and PIS amended to v3.0 & v2.0 |
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19 Jun 2015 |
Participant Information Sheet V4,
,Informed Consent Form V3
Supplementary Protocol added to study
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22 Jun 2015 |
GP cover letter version 1 dated 22/06/15
Additional info for attaching to letter above, version 1 dated 22nd june 2015
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23 Jun 2015 |
Protocol updated to version 4.0, dated 18th June 2015 |
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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. | |||
None |