Circadian Phase Adjustment and Improvement of Metabolic Control in Night Shift Workers
Primary Purpose
Sleep Disorders, Circadian Rhythm
Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Melatonin 2mg
Placebo
Sponsored by
About this trial
This is an interventional prevention trial for Sleep Disorders, Circadian Rhythm focused on measuring Type 2 Diabetes, metabolic control, Metabolomics, Circadian Rhythm, Melatonin, Biomarker, Clock Gene, PBMC, Cardiovascular function, Epigenetic modification, Lifestyle Intervention
Eligibility Criteria
Inclusion Criteria:
- Male and female above the age of 18
- Night shift workers on regular night shifts (at least 6 months before inclusion into the study and at least 4 night shifts per month during the study period
Exclusion Criteria:
- pregnancy or breast feeding
- Known autoimmune disease
- Current or relevant history of physical or psychiatric illness
- Evidence of renal insufficiency or liver disease
- Known or suspected intolerance or hypersensitivity to the study medication
- Use of certain drugs within 4 weeks prior to the inclusion to the study
Sites / Locations
- University Medical Center Aachen
- CTC North GmbH & Co. KG
- Department of Systems Medicine
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Placebo Comparator
Arm Label
Melatonin 2mg
Placebo
Arm Description
The study medication will be compared to placebo control.
The study medication will be compared to placebo control.
Outcomes
Primary Outcome Measures
Efficacy (AUC)
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.
Secondary Outcome Measures
Efficacy BMI
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.
Efficacy expression pattern of clock genes
The change in the gene expression patterns of Clock genes in peripheral blood monocytic cells (PBMC) between baseline and 12 weeks of intervention and between week 12 and 24.
Efficacy glucose homeostasis (HOMA-index)
The change in the HOMA-index (Homeostasis Model Assessment) between baseline and 12 weeks of intervention and between week 12 and 24.
Efficacy glucose homeostasis (QUICKI-index)
The change in the QUICKI-index (quantitative insulin sensitivity check index) between baseline and 12 weeks of intervention and between week 12 and 24.
Efficacy glucose homeostasis (Stumvoll ISI-index)
The change in HbA1c between baseline and 12 weeks of intervention and between week 12 and 24.
Efficacy glucose homeostasis (HbA1c)
The change in the Stumvoll ISI (Stumvoll insulin sensitivity index) between baseline and 12 weeks of intervention and between week 12 and 24.
Efficacy epigenetic profiles
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.
Efficacy biomarkers
The differences in plasma and serum biomarkers between baseline and 12 weeks of intervention and between week 12 and 24.
Efficacy AUC Insulin 24 weeks
The change in the area under the curve (AUC) of blood insulin during an oral glucose tolerance test between week 12 and week 24 (= after 12 weeks without intervention).
Efficacy AUC glucose 24 weeks
The change in the area under the curve (AUC) of blood glucose during an oral glucose tolerance test between week 12 and week 24 (= after 12 weeks without intervention).
Efficacy AUC insulin 12 weeks
The change in the area under the curve (AUC) of blood insulin during an oral glucose tolerance test between baseline and 12 weeks of intervention.
Full Information
NCT ID
NCT02108353
First Posted
November 4, 2013
Last Updated
May 24, 2017
Sponsor
Universitätsklinikum Hamburg-Eppendorf
1. Study Identification
Unique Protocol Identification Number
NCT02108353
Brief Title
Circadian Phase Adjustment and Improvement of Metabolic Control in Night Shift Workers
Official Title
Multicenter, Randomized, Double-blind, Placebo Controlled Trial of 2 mg Melatonin for Circadian Phase Adjustment and Improvement of Metabolic Control in Night Shift Workers
Study Type
Interventional
2. Study Status
Record Verification Date
May 2017
Overall Recruitment Status
Completed
Study Start Date
January 2015 (undefined)
Primary Completion Date
March 29, 2017 (Actual)
Study Completion Date
March 29, 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Universitätsklinikum Hamburg-Eppendorf
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
EuRhythDia II is a multicenter, randomized, double-blind controlled study. The rationale of EuRhythdia is to explore the effects of 12 weeks of timed melatonin treatment on circadian rhythm, metabolic control and cardiovascular function in night shift workers. The 12 weeks of intervention will be followed by 12 weeks of washing out.
Detailed Description
Modern lifestyle has dramatically changed the daily rhythms of life. Physical activity, diet and light exposure are no longer restricted to daytime hours due to increased shift work. Recent scientific reports have shown that shift work leads to disruption of circadian rhythms and promotes diabetes, obesity and cardiovascular disease. Until now only few studies investigating circadian rhythm disturbances in the context of type 2 diabetes and obesity have been conducted in man. Thus, knowledge of the molecular pathways and the responsibles genes in man are missing and have been identified only in animal studies.
The objective of the project is to achieve breakthroughs in the understanding of the causality between inner clock rhythm disturbances and the development of type 2 diabetes and obesity. The provided data on the interaction between genes, epigenetics, metabolism, cardiovascular function and the internal clock are intended to contribute to identify novel biomarkers and novel therapeutic approaches focusing on circadian rhythms to reduce the occurence of diabetes and obesity in shift worker.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Sleep Disorders, Circadian Rhythm
Keywords
Type 2 Diabetes, metabolic control, Metabolomics, Circadian Rhythm, Melatonin, Biomarker, Clock Gene, PBMC, Cardiovascular function, Epigenetic modification, Lifestyle Intervention
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
46 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Melatonin 2mg
Arm Type
Active Comparator
Arm Description
The study medication will be compared to placebo control.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
The study medication will be compared to placebo control.
Intervention Type
Drug
Intervention Name(s)
Melatonin 2mg
Other Intervention Name(s)
Circadin®
Intervention Description
once daily, 0.5-1 hours before going to bed and 1-2 hours after the last meal for 12 weeks.
Intervention Type
Drug
Intervention Name(s)
Placebo
Other Intervention Name(s)
None active substances
Intervention Description
once daily, 0.5-1 hours before going to bed and 1-2 hours after the last meal for 12 weeks.
Primary Outcome Measure Information:
Title
Efficacy (AUC)
Description
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.
Time Frame
baseline and 12 weeks
Secondary Outcome Measure Information:
Title
Efficacy BMI
Description
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.
Time Frame
baseline, 12 weeks and 24 weeks
Title
Efficacy expression pattern of clock genes
Description
The change in the gene expression patterns of Clock genes in peripheral blood monocytic cells (PBMC) between baseline and 12 weeks of intervention and between week 12 and 24.
Time Frame
baseline, 12 weeks and 24 weeks
Title
Efficacy glucose homeostasis (HOMA-index)
Description
The change in the HOMA-index (Homeostasis Model Assessment) between baseline and 12 weeks of intervention and between week 12 and 24.
Time Frame
baseline, 12 weeks and 24 weeks
Title
Efficacy glucose homeostasis (QUICKI-index)
Description
The change in the QUICKI-index (quantitative insulin sensitivity check index) between baseline and 12 weeks of intervention and between week 12 and 24.
Time Frame
baseline, 12 weeks and 24 weeks
Title
Efficacy glucose homeostasis (Stumvoll ISI-index)
Description
The change in HbA1c between baseline and 12 weeks of intervention and between week 12 and 24.
Time Frame
baseline, 12 weeks and 24 weeks
Title
Efficacy glucose homeostasis (HbA1c)
Description
The change in the Stumvoll ISI (Stumvoll insulin sensitivity index) between baseline and 12 weeks of intervention and between week 12 and 24.
Time Frame
baseline, 12 weeks and 24 weeks
Title
Efficacy epigenetic profiles
Description
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.
Time Frame
12 weeks and 24 weeks
Title
Efficacy biomarkers
Description
The differences in plasma and serum biomarkers between baseline and 12 weeks of intervention and between week 12 and 24.
Time Frame
baseline, 12 weeks and 24 weeks
Title
Efficacy AUC Insulin 24 weeks
Description
The change in the area under the curve (AUC) of blood insulin during an oral glucose tolerance test between week 12 and week 24 (= after 12 weeks without intervention).
Time Frame
12 weeks and 24 weeks
Title
Efficacy AUC glucose 24 weeks
Description
The change in the area under the curve (AUC) of blood glucose during an oral glucose tolerance test between week 12 and week 24 (= after 12 weeks without intervention).
Time Frame
12 weeks and 24 weeks
Title
Efficacy AUC insulin 12 weeks
Description
The change in the area under the curve (AUC) of blood insulin during an oral glucose tolerance test between baseline and 12 weeks of intervention.
Time Frame
baseline and 12 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Male and female above the age of 18
Night shift workers on regular night shifts (at least 6 months before inclusion into the study and at least 4 night shifts per month during the study period
Exclusion Criteria:
pregnancy or breast feeding
Known autoimmune disease
Current or relevant history of physical or psychiatric illness
Evidence of renal insufficiency or liver disease
Known or suspected intolerance or hypersensitivity to the study medication
Use of certain drugs within 4 weeks prior to the inclusion to the study
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Rainer H Boeger, MD
Organizational Affiliation
Universitätsklinikum Hamburg-Eppendorf
Official's Role
Study Chair
Facility Information:
Facility Name
University Medical Center Aachen
City
Aachen
State/Province
North Rhine-Westphalia
ZIP/Postal Code
52074
Country
Germany
Facility Name
CTC North GmbH & Co. KG
City
Hamburg
ZIP/Postal Code
20246
Country
Germany
Facility Name
Department of Systems Medicine
City
Rome
State/Province
Lazio
ZIP/Postal Code
00133
Country
Italy
12. IPD Sharing Statement
Links:
URL
http://eurhythdia.eu
Description
Trial homepage
Learn more about this trial
Circadian Phase Adjustment and Improvement of Metabolic Control in Night Shift Workers
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