Using Early Time Restricted Feeding and Timed Light Therapy to Improve Glycemic Control in Adults With Type 2 Diabetes

• ClinicalTrials.gov Identifier: NCT04155619
• Recruitment Status: Recruiting
• First Posted: November 7, 2019
• Last Update Posted: May 16, 2023
• Sponsor: University of Alabama at Birmingham
• Information provided by (Responsible Party): Courtney M Peterson, University of Alabama at Birmingham

Tracking Information

• First Submitted Date: November 5, 2019
• First Posted Date: November 7, 2019
• Last Update Posted Date: May 16, 2023
• Actual Study Start Date: April 26, 2021
• Estimated Primary Completion Date: August 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 5, 2019)

• 24-hour glucose levels [ Time Frame: 16 weeks ]
  Time-weighted mean, fasting, peak, standard deviation, and excursion (maximum - minimum) values (mg/dl)
• 24-hour insulin levels [ Time Frame: 16 weeks ]
  Time-weighted mean, fasting, peak, standard deviation, and excursion values (mU/l)
• 24-hour C-peptide levels [ Time Frame: 16 weeks ]
  Time-weighted mean, fasting, peak, standard deviation, and excursion values (pmol/l). This is also a proxy for total 24-hour insulin secretion.
• Hemoglobin A1C [ Time Frame: 16 weeks ]
• Insulin sensitivity [ Time Frame: 16 weeks ]
  Insulin sensitivity (dl/kg/min/μU/ml) during three identical meal tolerance tests, as measured by the Oral Minimal Model. The individual, mean, and excursion values, and time of the peak value will also be calculated.
• Beta-cell responsivity index (a measure of beta-cell function) [ Time Frame: 16 weeks ]
  Beta-cell responsivity during three identical meal tolerance tests, as measured by the Oral Minimal Model. The individual, mean, and excursion values, and time of the peak value will also be calculated.
• Insulin secretion [ Time Frame: 16 weeks ]
  Insulin secretion (mU) across three identical meal tolerance tests, as measured by the Oral Minimal Model. The individual, mean, and excursion values, and time of the peak value will also be calculated.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: December 25, 2019)

• Melatonin Amplitude [ Time Frame: 16 weeks ]
  Peak value (pg/mL)
• Cortisol Amplitude [ Time Frame: 16 weeks ]
  Amplitude (μg/dl)
• Melatonin Phase [ Time Frame: 16 weeks ]
  Clock time of dim light melatonin onset (DLMO)
• Cortisol Phase [ Time Frame: 16 weeks ]
  Clock time of cortisol phase
• Glycemic ("Peripheral") Rhythm Amplitude [ Time Frame: 16 weeks ]
  Amplitude or diurnal variation in glucose levels (mg/dl) during a constant glucose infusion procedure
• Glycemic ("Peripheral") Rhythm Phase [ Time Frame: 16 weeks ]
  Time of day that glucose levels experience a nadir during a constant glucose infusion procedure

Original Secondary Outcome Measures (submitted: November 5, 2019)

• Melatonin Amplitude [ Time Frame: 16 weeks ]
  Peak value (pg/mL)
• Cortisol Amplitude [ Time Frame: 16 weeks ]
  Ampitude (μg/dl)
• Melatonin Phase [ Time Frame: 16 weeks ]
  Clock time of dim light melatonin onset (DLMO)
• Cortisol Phase [ Time Frame: 16 weeks ]
  Clock time of cortisol phase
• Glycemic ("Peripheral") Rhythm Amplitude [ Time Frame: 16 weeks ]
  Amplitude or diurnal variation in glucose levels (mg/dl) during a constant glucose infusion procedure
• Glycemic ("Peripheral") Rhythm Phase [ Time Frame: 16 weeks ]
  Time of day that glucose levels experience a nadir during a constant glucose infusion procedure

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Using Early Time Restricted Feeding and Timed Light Therapy to Improve Glycemic Control in Adults With Type 2 Diabetes
• Official Title: Using Early Time Restricted Feeding and Timed Light Therapy to Improve Glycemic Control in Adults With Type 2 Diabetes
• Brief Summary: The purpose of this study is to test whether eating earlier in the day and/or timed light therapy can improve blood sugar in people with type 2 diabetes. This study will also test whether these treatments improve other aspects of health, including the circadian (biological) clock, sleep, weight, body composition, cardiovascular health, quality of life, and mood.

Detailed Description

The circadian system is strongly linked to type 2 diabetes. Adults with type 2 diabetes have circadian rhythms that are both weakened and mistimed. Weak rhythms may be due to insufficient bright light exposure during the daytime, irregular meal timing, or grazing on food throughout the day. Mistiming may be due to ill-timed food intake or light exposure-such as eating later in the day or light exposure at night-which causes central and peripheral circadian clocks within the body to become out of sync (circadian misalignment). This circadian misalignment impairs glucose metabolism: data now show that eating late in the day and light exposure at night rapidly elevate glucose (blood sugar) and insulin levels in humans within days. Conversely, well-timed food intake and light exposure appear to improve glycemic (blood sugar) control, circadian rhythms, and several other aspects of health.

This study will test the health effects of eating early in the daytime (early time-restricted feeding; early TRF) and timed light therapy in adults with type 2 diabetes. The study will test the following aims:

1. Determine whether early TRF and/or timed light therapy improve glycemic control
2. (a) Determine how early TRF and/or timed light therapy affect the central and peripheral circadian clocks and (b) determine which patients benefit the most from circadian-based therapies
3. Determine whether early TRF and/or timed light therapy improve sleep, body weight, body composition, cardiovascular risk factors, quality of life, and psychological health.

Approximately 344 veterans and civilians aged 30-80 with insulin-independent type 2 diabetes will be randomized to the following 2 x 2 study design:

1. No change in eating or light exposure habits
2. Early TRF
3. Timed light therapy
4. Early TRF and timed light therapy

Participants will be asked to follow their assigned treatment for 16 weeks and then be followed up for an additional eight months (1 year in total). Baseline and post-intervention testing will be conducted during a 38-hour inpatient (hospital) stay. Testing will involve three 3-hour meal tolerance tests to determine insulin sensitivity and secretion; 24-hour measurement of glucose, insulin, and C-peptide levels; 24-hour measurement of cortisol and melatonin to measure the phase and amplitude of the central clock; and a constant glucose infusion to determine the phase and amplitude of the effective glycemic ("peripheral") circadian clock. Sleep, weight loss, body composition, and cardiovascular risk factors will also be measured, and questionnaires and an interview will be administered to determine improvements in quality of life and psychological health.

Note: Pre-registered primary and secondary outcomes are listed below. Pre-registered tertiary outcomes appear in the study protocol, which will be uploaded to this website.

• Study Type: Interventional
• Study Phase: Not Applicable

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Investigator)
Masking Description:

The study statistician will be blinded. To the degree possible for each task, other study staff will be blinded during outcome assessments and analysis.

Primary Purpose: Treatment

Condition

• Diabetes Mellitus, Type 2
• Time Restricted Feeding
• Light; Therapy, Complications

Intervention

• Behavioral: No change in meal timing
  Participants will eat within an ≥11-hour daily period (no change in meal timing habits).
• Behavioral: No change in light exposure
  Participants will not change their light exposure habits.
• Behavioral: Early Time-Restricted Feeding
  Participants will eat within an 8-hour daily period early in the day, starting within 2 hours of waking up.
  Other Name: eTRF, early TRF
• Behavioral: Timed Light Therapy
  Participants will use bright light therapy for 60 minutes between 6 am - 3 pm, blue light-blocking glasses for one hour before bedtime, and blackout curtains at night.
  Other Name: Bright Light Therapy

Study Arms

• Active Comparator: No change in eating or light exposure habits
  Interventions:

  • Behavioral: No change in meal timing
  • Behavioral: No change in light exposure
• Experimental: Early Time-Restricted Feeding
  Interventions:

  • Behavioral: No change in light exposure
  • Behavioral: Early Time-Restricted Feeding
• Experimental: Timed Light Therapy
  Interventions:

  • Behavioral: No change in meal timing
  • Behavioral: Timed Light Therapy
• Experimental: Early Time-Restricted Feeding and Timed Light Therapy
  Interventions:

  • Behavioral: Early Time-Restricted Feeding
  • Behavioral: Timed Light Therapy

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: November 5, 2019): 344
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: August 2025
• Estimated Primary Completion Date: August 2025 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Aged 30-80 years old
• HbA1c between 7.0 - 10.0%
• On a stable dose of metformin, sulfonylureas, DPP-IV inhibitors, and/or GLP-1 receptor agonists for at least 6 months, or taking no diabetes medications
• Stable values of HbA1c for the past 6 months (within 0.7%)
• Wake up at a regular time between 5-9 am

Exclusion Criteria:

• On insulin or diabetes medication other than metformin, sulfonylureas, DPP-IV inhibitors, and/or GLP-1 receptor agonists
• Have type 1 diabetes or was diagnosed with diabetes before age 18
• Moderate or severe retinopathy or other medical condition that may affect the ability to safely receive bright light therapy
• A history of severe hypoglycemia
• Change in the dosage of a chronic medication within the past 2 months
• Have a clinically significant laboratory abnormality (e.g., abnormal hemoglobin levels)
• Severe gastrointestinal disease, major gastrointestinal surgery, or gallstones
• Cardiovascular, renal, cardiac, liver, lung, adrenal, or nervous system disease that is unstable or may compromise study validity
• Evidence of cancer (other than non-melanoma skin cancer) within the last 5 years
• Pregnant or breastfeeding
• Current diagnosis of a major psychiatric condition that would impair study participation
• Diagnosed sleep disorder or circadian disorder that is not stabilized
• Spend an average of more than 1.5 hours/day outdoors
• Perform overnight shift work more than 1 day/week on average
• Regularly eat within a less than a 10-hour period daily
• Regularly finish eating dinner before 5:30 pm
• Lost or gained more than 3 kg (6.6 lbs) of weight in the past 3 months
• Traveled more than two times zones away in the two months prior to enrolling in the trial or will travel more than two time zones away during the 16-week study

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 30 Years to 80 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Courtney Peterson, Ph.D.; 205-934-0122; cpeterso@uab.edu

Contact: Ralee' Bunt, B.S.; 205-975-3944; erikabunt@uabmc.edu

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04155619
• Other Study ID Numbers: IRB-300003964
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes

• Current Responsible Party: Courtney M Peterson, University of Alabama at Birmingham
• Original Responsible Party: Same as current
• Current Study Sponsor: University of Alabama at Birmingham
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Courtney Peterson, Ph.D.; University of Alabama at Birmingham

• PRS Account: University of Alabama at Birmingham
• Verification Date: May 2023