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Completed

NCT Number: NCT03490864

Strengthening Circadian Signals

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.

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Key information

Conditions

Improving Cardiometabolic Outcomes in Adults

Age range

35 year–54 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Northwestern University

Chicago, Illinois, 60611, United States

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Adults 35-54 years old.
  • BMI ≥25 to <45
  • 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 ≥30
  • 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
  • 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.

Treatment and study plan

Melatonin 1 mg

Dietary Supplement

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.

Placebos

Dietary Supplement

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.

Meal timing

Other

Subjects are instructed to maintain an extended overnight fasting period of 12-16 hours.

Other names: Extended overnight fasting (EOF)

NON Meal Timing

Other

Subjects are instructed to maintain their habitual meal timing.

Other names: NON Extended overnight fasting (nEOF)

Primary outcomes

  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.

Sponsors and collaborators

Lead sponsor

Northwestern University

Other

Registry information

Official study title

Strengthening Circadian Signals to Enhance Cardiometabolic Functions

Important dates

Study start
2018
Primary completion
2024
Study completion
2024
First posted
Apr 6, 2018
Registry last updated
May 23, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.