Aging Program Project Grant 6 (PPG6)

Enhancing Circadian Signal to Improve Cardiometabolic Function in Aging

This study aims to enhance circadian signals to improve cardiometabolic functions in older adults though meal timing interventions and melatonin supplements. Cardiometabolic disease (CMD) is prevalent among older adults, but despite vigorous research to prevent it, it remains on of the greatest public health challenges. Previous research has shown that extended overnight fasting and melatonin supplements may enhance circadian signals which in turn would enhance cardiometabolic function in older adults.

This study will place subjects in one of four intervention groups, 1) Meal timing + Melatonin, 2) Meal timing + Placebo, 3) Melatonin, or 4) Placebo in order test out the effects of meal timing and melatonin both separately and together and cardio metabolic functions. The study will explore the effects of these interventions in acute-based setting and extended-based settings. This will allow us to test out the hypotheses of the study that meal timing can improve amplitude of circadian signals and improve cardiometabolic functions and sleep quality as well as melatonin improving cardiometabolic function and sleep quality. Finally, we will determine if the the addition of melatonin will further enhance the effects of the meal timing intervention for improving cardiometabolic function and sleep.

Study Overview

• Status: Recruiting
• Conditions: Improving Cardiometabolic Outcomes in Older Adults
• Intervention / Treatment: Dietary supplement: Melatonin 1 mg; Other: Meal timing; Dietary supplement: Placebos; Other: Non-Meal timing

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Phyllis Zee, MD, PhD; Phone Number: 312-503-4409; Email: p-zee@northwestern.edu
• Study Contact Backup: Name: Kathyrn Reid, PhD; Phone Number: 312-503-1528; Email: k-reid@northwestern.edu

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Recruiting
      • Northwestern University
      • Contact: Kathyrn Reid, PhD; Phone Number: 312-503-1528; Email: k-reid@northwestern.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 55 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Older adults 55-75 years old.
• Females must be post-menopausal.
• BMI 25-45
• Regular eating schedule (consuming at least 2 meals/day) and sleeping schedules (deviation of ≤ 2 hours in daily mid-sleep time).
• Self-report sleep duration of ≥ 6.5 hours.
• Habitual mid-sleep time of 1-5 am.
• Habitual time in bed less than 9 hours
• HbA1c <6.5
• Habitual overnight fast of ≤ 13 hour (Determined by a mean overnight fast ≤ 13 hours over 3 days of self-monitoring of food intake)

Exclusion Criteria:

• History or current diagnosis of a primary sleep disorder (Chronic insomnia, restless leg syndrome, parasomnias, sleep apnea).
• AHI ≥30
• History of 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.
• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / 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 16 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) 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 12-16 hours.; Other Names: 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 16 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/Starch) supplementation given daily during the intervention.	Other: Meal timing; Subjects are instructed to maintain an extended overnight fasting period of 12-16 hours.; Other Names: Extended overnight fasting (EOF); Dietary supplement: Placebos; Placebo will be administered daily during the intervention. The investigational drug pharmacy (IDP) at Northwestern Memorial Hospital will encapsulate the pills so the placebo (lactose/starch) 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.
Experimental: Melatonin; This arm will continue to eat at their habitual meal times, and maintain their average habitual caloric and macronutrient intake. No EOF will be imposed. This arm will include a 1mg melatonin supplementation given daily during the intervention.	Dietary supplement: Melatonin 1 mg; Melatonin (1mg) 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 Names: 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 EOF will be imposed. This arm will also include a melatonin placebo (Lactose/Starch) supplementation given daily during the intervention.	Dietary supplement: Placebos; Placebo will be administered daily during the intervention. The investigational drug pharmacy (IDP) at Northwestern Memorial Hospital will encapsulate the pills so the placebo (lactose/starch) 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 Names: Non-extended overnight fasting (nEOF)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Matsuda Index	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.	8 weeks
Nocturnal Blood Pressure Dipping	Defined as a ratio of sleep blood pressure to wake blood pressure less than 0.90.	8 weeks
Melatonin Amplitude	The melatonin amplitude will be calculated to determine the effects of the interventions on sleep and CMD outcomes.	8 weeks

Collaborators and Investigators

• Sponsor: Northwestern University
• Investigators: Principal Investigator: Phyllis Zee, MD, PhD, Northwestern University

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2018
• Primary Completion (Estimated): May 31, 2024
• Study Completion (Estimated): May 31, 2024

Study Registration Dates

• First Submitted: March 30, 2018
• First Submitted That Met QC Criteria: March 30, 2018
• First Posted (Actual): April 6, 2018

Study Record Updates

• Last Update Posted (Actual): March 18, 2024
• Last Update Submitted That Met QC Criteria: March 14, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Protective Agents; Antioxidants; Melatonin
• Other Study ID Numbers: STU00206014

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• 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