Clinical trial NCT04057339: The Influence of Time-Restricted Eating in Patients With Metabolic Syndrome
Official title: Influence of Time-restricted Eating (TRE) on Circadian Regulation of Glucose Homeostasis and Mitochondrial Function - The TIMET Study
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Metabolic Syndrome
Pre-Diabetes
Keywords: Time Restricted Eating
Circadian Rhythm
Glucose Homeostasis
Mitochondrial Function
Fasting
Lead sponsor: University of California, San Diego
Sponsor class: OTHER
Collaborators: name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
name: Salk Institute for Biological Studies
First posted: 2019-08-15
Enrollment: 122
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: In a randomized controlled trial, the investigators intend to measure the health impact of TRE in patients with metabolic syndrome (with three or more of the following criteria: increased waist circumference, abnormal cholesterol levels, elevated blood pressure, or elevated blood sugar), who habitually eat for more than 14 hours every day. Patients will be randomly assigned to a control group of behavioral nutrition counseling (standard of care) or the intervention group of behavioral nutrition counseling with the addition of adopting a 8-10 hour eating window for 12 weeks (TRE).

Detailed description: Circadian rhythms optimize nutrient homeostasis by orchestrating catabolic and anabolic metabolism to appropriate times of the 24 hour day. Chronic circadian rhythm disruption predisposes individuals to metabolic diseases including obesity and type 2 diabetes. Conversely, maintaining a daily rhythm of feeding and fasting cycles sustains a robust circadian rhythm which improves cellular bioenergetics and results in improved metabolism. Time-restricted eating (TRE) is a specific feeding-fasting pattern in which feeding is restricted to 8-12 hours a day.

At the beginning and end of the study (which will be three months in duration), the following parameters will be measured: height, weight, body mass index, percent body fat, waist/hip circumference and blood pressure. Blood sugar levels will be monitored continuously for 2 weeks at a time at the beginning and end of the study using a continuous glucose monitor. Additionally, a dual energy X-ray absorptiometry (DXA) scan will be used to collect information about body composition. Information will be collected about the mitochondria with a muscle biopsy. Participants will use a smartphone application (called myCircadianClock (mCC), developed by the Salk Institute) to keep track of food/beverage intake and will wear a wrist-worn actigraphy device to monitor physical activity levels and sleep.

Eligibility criteria: Inclusion Criteria:

1. Age 18-75 years
2. 41 ≥ BMI ≥ 25 AND
3. Metabolic syndrome, as defined as presence of 3 or more of the following criteria:

   Elevated fasting plasma glucose ≥ 100 mg/dL and/or HbA1c ≥ 5.7% \< 7.1% Elevated waist circumference: In Asians: ≥ 90 cm in men, ≥ 80 cm in women, all other races: ≥ 102 cm in men, ≥ 88 cm in women Fasting plasma triglycerides ≥ 150 mg/dL, or on drug treatment for elevated triglycerides Reduced High-density lipoprotein (HDL)-cholesterol \< 40 mg/dL in males or \< 50 mg/dL in females, or drug treatment for reduced HDL-cholesterol Elevated blood pressure, Systolic blood pressure ≥ 135 mm Hg and/or diastolic blood pressure ≥ 85 mm Hg or drug treatment for hypertension
4. Own a smartphone (Apple iOS or Android OS)
5. Baseline eating period ≥ 12 hour window
6. If patients are on cardiovascular medications (HMG CoA reductase inhibitors (statins), other lipid modifying drugs (including over the counter drugs such as red yeast rice and fish oil), anti-hypertensive, anti-diabetes drugs), no dose adjustments will be allowed during the study period.

Exclusion Criteria:

1. Taking insulin within the last 6 months.
2. Manifest diabetes, defined as HbA1c \> 7.0% given a 0.3% margin of error in lab readings, or diagnosis of diabetes.
3. Known inflammatory and/or rheumatologic disease.
4. Active tobacco abuse or illicit drug use or history of treatment for alcohol abuse.
5. Pregnant or breast-feeding women.
6. Shift workers with variable (e.g. nocturnal) hours.
7. Caregivers for dependent requiring frequent nocturnal care/sleep interruptions.
8. Planned travel to a time zone with greater than a 3-hour difference during study period.
9. History of major adverse cardiovascular event within the past 1 year (acute coronary syndrome (ACS), percutaneous coronary intervention, coronary artery bypass graft surgery, hospitalization for congestive heart failure, stroke/transient ischemic attack (TIA)).
10. Uncontrolled arrhythmia (i.e. rate-controlled atrial fibrillation/atrial flutter are not exclusion criteria).
11. History of thyroid disease requiring dose titration of thyroid replacement medication(s) within the past 3 months (i.e. hypothyroidism on a stable dose of thyroid replacement therapy is not an exclusion).
12. History of adrenal disease.
13. History of malignancy undergoing active treatment, except non-melanoma skin cancer.
14. Known history of type I diabetes.
15. History of eating disorder(s).
16. History of cirrhosis.
17. History of stage 4 or 5 chronic kidney disease or requiring dialysis.
18. History of HIV/AIDS.
19. Currently enrolled in a weight-loss or weight-management program.
20. On a special or prescribed diet for other reasons (e.g. Celiac disease).
21. Currently taking any medication that is meant for, or has known effect on, appetite.
22. Any history of surgical intervention for weight management.
23. Uncontrolled psychiatric disorder (including history of hospitalization for psychiatric illness).
24. A score of \>16 on the Epworth Sleepiness Scale (ESS).
25. Depression determined by the Beck Depression Inventory (BDI) (unless previously diagnosed and well-controlled).
26. Failure to use the smartphone app for documentation (defined as \<2 meals/day for ≥3 days during baseline).

Primary outcomes:
measure: Change in glucose levels assessed via HbA1c
timeFrame: Baseline and 14 weeks
measure: Change in glycemic parameters
timeFrame: Baseline and 14 weeks
Secondary outcomes:
measure: Change in LDL particle number
timeFrame: Baseline and 14 weeks
measure: Change in LDL cholesterol
timeFrame: Baseline and 14 weeks
measure: Change in HDL cholesterol
timeFrame: Baseline and 14 weeks
measure: Change in Triglycerides
timeFrame: Baseline and 14 weeks
measure: Change in body composition by DXA
timeFrame: Baseline and 14 weeks
measure: Change in hs-CRP
timeFrame: Baseline and 14 weeks
Other outcomes:
measure: Change in mitochondrial structure and gene expression in skeletal muscle
timeFrame: Baseline and 14 weeks
Locations:
city: La Jolla
country: United States
facility: Altman Clinical and Translational Research Institute
state: California
Study officials:
affiliation: Associate Professor of Medicine
name: Pam Taub, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Taub PR, Panda S. Time for better time-restricted eating trials to lessen the burden of metabolic diseases. Cell Rep Med. 2022 Jun 21;3(6):100665. doi: 10.1016/j.xcrm.2022.100665.