Clinical trial NCT04155619: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Diabetes Mellitus, Type 2
Time Restricted Feeding
Light; Therapy, Complications
Lead sponsor: University of Alabama at Birmingham
Sponsor class: OTHER
First posted: 2019-11-07
Enrollment: 344
Sex: ALL
Minimum age (years): 30
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

* Aged 30-80 years old
* Have type 2 diabetes
* HbA1c between 5.7 - 12.0%
* On a stable dose of metformin, DPP-IV inhibitors, SGLT2 inhibitors, sulfonylureas, and/or GLP-1 receptor agonists for at least 6 weeks, or taking no diabetes medications
* Wake up at a regular time between 5-9 am

Exclusion Criteria:

* On insulin or diabetes medication other than metformin, DPP-IV inhibitors, SGLT2 inhibitors, sulfonylureas, 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 month (need to wait at least 1 month prior to baseline visit)
* Have a clinically significant laboratory abnormality (e.g., abnormal hemoglobin levels)
* Severe gastrointestinal disease, major gastrointestinal surgery, or active gallstone disease
* 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 (sleep apnea is allowed). Those with narcolepsy will not be included.
* Major changes in health or medical history in the last 3 months that could affect data validity per judgement of the study physician
* 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 6:30 pm
* Lost or gained more than 8 lbs within the last 2 months and weight needs to be stable for a minimum of 4 weeks before baseline testing
* 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

Primary outcomes:
measure: 24-hour glucose levels
timeFrame: 16 weeks
measure: 24-hour insulin levels
timeFrame: 16 weeks
measure: 24-hour C-peptide levels
timeFrame: 16 weeks
measure: Hemoglobin A1C
timeFrame: 16 weeks
measure: Insulin sensitivity
timeFrame: 16 weeks
measure: Beta-cell responsivity index (a measure of beta-cell function)
timeFrame: 16 weeks
measure: Insulin secretion
timeFrame: 16 weeks
Secondary outcomes:
measure: Melatonin Amplitude
timeFrame: 16 weeks
measure: Cortisol Amplitude
timeFrame: 16 weeks
measure: Melatonin Phase
timeFrame: 16 weeks
measure: Cortisol Phase
timeFrame: 16 weeks
measure: Glycemic ("Peripheral") Rhythm Amplitude
timeFrame: 16 weeks
measure: Glycemic ("Peripheral") Rhythm Phase
timeFrame: 16 weeks
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham; Birmingham Veterans Affairs Medical Center
state: Alabama
Study officials:
affiliation: University of Alabama at Birmingham
name: Courtney Peterson, Ph.D.
role: PRINCIPAL_INVESTIGATOR
References: