Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Strengthening Circadian Signals

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03490864
Recruitment Status : Recruiting
First Posted : April 6, 2018
Last Update Posted : August 22, 2019
Sponsor:
Information provided by (Responsible Party):
Phyllis Zee, Northwestern University

Brief Summary:

There is a growing body of evidence from both laboratory and field studies that disrupted circadian function, particularly decreased amplitude and stability of rhythmic behaviors represent significant risk factors for cardiometabolic disease (CMD) in humans. The exciting evidence of the ubiquity of circadian clocks in all tissues and their critical role in metabolism, not only opens up new avenues for understanding the mechanistic interactions between central and peripheral clocks in cardiometabolic disease pathogenesis, but also to develop therapeutic interventions to re-establish synchrony between central and peripheral clocks with each other and with the external physical and social environments. Feeding has been shown to synchronize clocks in peripheral tissues. Animal studies have demonstrated that restricting feeding to the active period decreases CMD risk, while in humans decreased caloric intake in the evening is associated with a lower body mass index (BMI). The amplitude of melatonin can be considered a marker of robustness of central circadian function, but melatonin also has physiological effects beyond circadian regulation throughout the body. Recent observations have demonstrated that having a low melatonin level is a risk factor for incident diabetes and hypertension independent of sleep duration. Together, the evidence suggests that strategies aimed at synchronizing feeding behavior and enhancing the nocturnal melatonin signal can positively impact cardiometabolic function.

We propose to take an innovative approach that combines the recent data on the role of feed/fast patterns on clock regulated metabolic activity and the reemergence of scientific interest of the central and peripheral effects of melatonin on cardiometabolic function to elucidate the physiological and molecular mechanisms that underlie the relationship between circadian dysregulation and obesity associated CMD risk. This will be accomplished by strengthening the amplitude of circadian metabolic signals via meal timing and enhancement of nocturnal circadian signaling with exogenous melatonin in overweight and obese middle aged and older adults. In addition, this study will provide crucial information regarding the importance of circadian timing for the design of future clinical trials on CMD in overweight and obese adults. This is a critical time in the lifespan when circadian based strategies for prevention and treatment are most likely to have the greatest impact on CMD risk. This project will enroll 100 adults (40-54 years) to participate in a parallel (4 arm intervention) placebo controlled study to determine whether a six- week program of meal timing and/or low dose (1 mg) melatonin administration will enhance circadian amplitude and enhance cardiometabolic function, as well as to evaluate the potential beneficial effects of a regimen that combines both approaches. The results from this study will demonstrate novel mechanistically based approaches for maintaining and improving circadian-metabolic health during a critical time in the lifespan when there is a rapid increase in the prevalence of CMD.


Condition or disease Intervention/treatment Phase
Improving Cardiometabolic Outcomes in Adults Dietary Supplement: Melatonin 1 mg Dietary Supplement: Placebos Other: Meal Timing Other: NON Meal Timing Not Applicable

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: The study is designed as a randomized controlled trial where each participant will receive one of four intervention types. Subjects will be randomized at baseline visit to one of four arms using a randomized block design to achieve balanced groups. Randomization will be stratified by sex. The allocation will be created using an online randomization tool. This study will include a 6 week four arm field intervention to evaluate the independent effect of meal of timing or melatonin as well as their combined effects.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
Official Title: Strengthening Circadian Signals to Enhance Cardiometabolic Functions
Actual Study Start Date : May 16, 2018
Estimated Primary Completion Date : June 30, 2022
Estimated Study Completion Date : November 30, 2022

Resource links provided by the National Library of Medicine

Drug Information available for: Melatonin

Arm Intervention/treatment
Experimental: Meal timing + Melatonin
This arm will consist of imposing a minimum overnight fasting period of 12 hours and a maximum of 14 hours (with exception of water and other non-caloric beverages), beginning 3 hours before their habitual bed time. This arm will also include a 1mg melatonin supplementation given daily during the intervention.
Dietary Supplement: Melatonin 1 mg
Melatonin (1mg) or placebo will be administered daily during the intervention. Melatonin capsules will be obtained from Life Extension (Ft. Lauderdale, FL). The investigational drug pharmacy (IDP) at Northwestern Memorial Hospital will encapsulate the melatonin pills so the placebo (lactose) and melatonin pills appear identical. We have worked with this IDP on other projects. The investigators on this study have experience in administering melatonin for investigational and clinical purposes.

Other: Meal Timing
Subjects are instructed to maintain an extended overnight fasting period of 12-14 hours.
Other Name: Extended overnight fasting (EOF)

Experimental: Meal timing + Placebo
This arm will consist of imposing a minimum overnight fasting period of 12 hours and a maximum of 14 hours (with exception of water and other non-caloric beverages), beginning 3 hours before their habitual bed time. This arm will also include a melatonin placebo (lactose) supplementation given daily during the intervention.
Dietary Supplement: Placebos
Melatonin (1mg) or placebo will be administered daily during the intervention. Melatonin capsules will be obtained from Life Extension (Ft. Lauderdale, FL). The investigational drug pharmacy (IDP) at Northwestern Memorial Hospital will encapsulate the melatonin pills so the placebo (lactose) and melatonin pills appear identical. We have worked with this IDP on other projects. The investigators on this study have experience in administering melatonin for investigational and clinical purposes.

Other: Meal Timing
Subjects are instructed to maintain an extended overnight fasting period of 12-14 hours.
Other Name: Extended overnight fasting (EOF)

Experimental: Melatonin
This arm will continue to eat at their habitual meal times, and maintain their average habitual caloric and macronutrient intake. No extended overnight fasting will be imposed. This arm will include a 1mg melatonin supplementation given daily during the intervention.
Dietary Supplement: Melatonin 1 mg
Melatonin (1mg) or placebo will be administered daily during the intervention. Melatonin capsules will be obtained from Life Extension (Ft. Lauderdale, FL). The investigational drug pharmacy (IDP) at Northwestern Memorial Hospital will encapsulate the melatonin pills so the placebo (lactose) and melatonin pills appear identical. We have worked with this IDP on other projects. The investigators on this study have experience in administering melatonin for investigational and clinical purposes.

Other: NON Meal Timing
Subjects are instructed to maintain their habitual meal timing.
Other Name: NON Extended overnight fasting (nEOF)

Placebo Comparator: Placebo
This arm will continue to eat at their habitual meal times, and maintain their average habitual caloric and macronutrient intake. No extended overnight fasting will be imposed. This arm will also include a melatonin placebo (lactose) supplementation given daily during the intervention
Dietary Supplement: Placebos
Melatonin (1mg) or placebo will be administered daily during the intervention. Melatonin capsules will be obtained from Life Extension (Ft. Lauderdale, FL). The investigational drug pharmacy (IDP) at Northwestern Memorial Hospital will encapsulate the melatonin pills so the placebo (lactose) and melatonin pills appear identical. We have worked with this IDP on other projects. The investigators on this study have experience in administering melatonin for investigational and clinical purposes.

Other: NON Meal Timing
Subjects are instructed to maintain their habitual meal timing.
Other Name: NON Extended overnight fasting (nEOF)




Primary Outcome Measures :
  1. Matsuda Index [ Time Frame: 8 Weeks ]
    The matsuda index of whole body index sensitivity will be calculated to explore the effect of sleep and circadian rhythms on the relationship between EOF, Melatonin, and CMD.

  2. Nocturnal Blood Pressure Dipping [ Time Frame: 8 Weeks ]
    Defined as a ratio of sleep Blood Pressure to wake Blood Pressure <0.90.

  3. Melatonin Amplitude [ Time Frame: 8 Weeks. ]
    The melatonin amplitude will be calculated to determine the effects of interventions on sleep and CMD outcomes.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   35 Years to 54 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Adults 35-54 years old.
  • BMI ≥25 to <40
  • Regular eating schedule

    • consuming at least 2 meals/day
  • Regular sleep schedules (deviation ≤2 hours in daily mid-sleep time)

    • self-reported average sleep duration of ≥6.5 hours,
    • habitual mid-sleep time 2-5am,
    • habitual time in bed of ≤ 9 hours,
  • Habitual overnight fast of ≤ 13 hour

    • Determined by a mean overnight fast ≤ 13 hours over 3 days of self-monitoring of food intake at screening
  • HbA1C<6.5

Exclusion Criteria:

  • History or current diagnosis of a primary sleep disorder (Chronic insomnia, restless leg syndrome, parasomnias, sleep apnea)
  • AHI ≥15
  • Current anemia
  • Diagnosis of diabetes or currently on any medications for diabetes.
  • Endocrine dysfunction including PCOS
  • History of cognitive or other neurological disorders
  • History of DSM-V criteria for any major psychiatric disorder
  • Night Eating Syndrome (NES)
  • Beck depression Index (BDI) of ≥16 indicating moderate depression
  • Mini mental status Exam <26 indicating cognitive impairment.
  • Unstable or serious medical conditions
  • Individuals with pacemakers, defibrillators, mediation pumps, or any other implanted device.
  • Any GI disease that requires dietary adjustment
  • Current or use within last month of melatonin
  • Current use of psychoactive, hypnotic, stimulants, or pain medications.
  • Current use of hormone replacement therapy
  • Current use of beta-blockers
  • Shift work or other self-imposed irregular sleep schedules.
  • History of habitual smoking (≥6 cigarettes/week)
  • Caffeine consumption >400 mg/day
  • Medically managed or self-reported weight loss program within past 6 months
  • Bariatric weight loss surgery.
  • Blindness or visual impairment other than glasses
  • Allergic to heparin.
  • Adults unable to consent will be excluded.
  • Pregnant women will be excluded.
  • Prisoners will be excluded.
  • Individuals who are not yet adults (infants, children, teenagers) will be excluded.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03490864


Contacts
Layout table for location contacts
Contact: Phyllis Zee, MD, PhD 3125034409 p-zee@northwestern.edu
Contact: Kathryn Reid, PhD 3125031528 k-reid@northwestern.edu

Locations
Layout table for location information
United States, Illinois
Northwestern University Recruiting
Chicago, Illinois, United States, 60611
Contact: Kathy Reid, PhD    312-503-1528    k-reid@northwestern.edu   
Sponsors and Collaborators
Northwestern University
Investigators
Layout table for investigator information
Principal Investigator: Phyllis Zee, MD, PhD Northwestern University

Layout table for additonal information
Responsible Party: Phyllis Zee, Professor of Neurology, Northwestern University
ClinicalTrials.gov Identifier: NCT03490864    
Other Study ID Numbers: STU00206038
First Posted: April 6, 2018    Key Record Dates
Last Update Posted: August 22, 2019
Last Verified: August 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Benzocaine
Melatonin
Anesthetics, Local
Anesthetics
Central Nervous System Depressants
Physiological Effects of Drugs
Sensory System Agents
Peripheral Nervous System Agents
Antioxidants
Molecular Mechanisms of Pharmacological Action
Protective Agents