ED14/11124

University of Leeds

Worsley Building, Leeds, United Kingdom, LS2 9LN

Clare Skinner, University of Leeds, 0113 3434897, c.e.skinner@leeds.ac.uk

Clare Skinner, University of Leeds, 0113 3434897, c.e.skinner@leeds.ac.uk

No

No

No

Final

23 Nov 2016

Yes

23 Nov 2016

Yes

01 Nov 2017

No

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

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.

01 Jul 2014

No

No

United Kingdom: 71

71

71

0

0

0

0

0

0

63

8

0

Overall Trial (overall period)

Randomised - controlled

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.

Yes

Oral Melatonin

Tablet

Oral use

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.

Placebo

Tablet

Oral use

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.

Melatonin Treatment

Placebo

Melatonin Treatment

Placebo

Primary

total study duration will be 26 months, with trial recruitment anticipated to be 12 months. This would leave 14 months for end point analysis.

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

4.0

Melatonin Treatment

Placebo