The Influence of Time-Restricted Eating in Patients With Metabolic Syndrome (TIMET)

• ClinicalTrials.gov Identifier: NCT04057339
• Recruitment Status: Recruiting
• First Posted: August 15, 2019
• Last Update Posted: January 3, 2022
• Sponsor: University of California, San Diego
• Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); Salk Institute for Biological Studies
• Information provided by (Responsible Party): Pam Taub, MD, University of California, San Diego

Study Description

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).

Condition or disease	Intervention/treatment	Phase
Metabolic Syndrome; Pre-Diabetes	Behavioral: Time Restricted Eating + Standard of Care; Behavioral: Standard of Care	Not Applicable

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 118 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Investigator)
• Primary Purpose: Treatment
• Official Title: Influence of Time-restricted Eating (TRE) on Circadian Regulation of Glucose Homeostasis and Mitochondrial Function - The TIMET Study
• Actual Study Start Date: April 8, 2019
• Estimated Primary Completion Date: June 2023
• Estimated Study Completion Date: June 2023

Arms and Interventions

Arm	Intervention/treatment
Placebo Comparator: SOC (Standard of Care); Everyone in this arm will receive standard of care nutritional behavioral counseling and will be required to log their caloric intake through the use of a smartphone app.	Behavioral: Standard of Care; Participants in this arm will receive nutritional counseling from the study dietician, but will not be required to adopt a 8-10-hr eating window.
Experimental: TRE + SOC; Everyone in this arm will receive standard of care nutritional behavioral counseling and will implement a daily 8-10-hour window within which they must consume their calories. They will also be required to log their caloric intake through the use of a smartphone app.	Behavioral: Time Restricted Eating + Standard of Care; Participants in this arm will adhere to a daily, consistent 8-10-hr eating window for the course of the study as well as receive nutritional counseling from the study dietitian.; Other Name: Time Restricted Eating

Outcome Measures

Primary Outcome Measures :

1. Change in glucose levels assessed via HbA1c [ Time Frame: Baseline and 14 weeks ]
   HbA1c (%)
2. Change in glycemic parameters [ Time Frame: Baseline and 14 weeks ]
   Glycemic parameters assessed via fasting glucose, HOMA-IR, Insulin, and continuous glucose monitors (CGM).

Secondary Outcome Measures :

1. Change in LDL particle number [ Time Frame: Baseline and 14 weeks ]
   LDL particle number (nmol/L) via NMR lipoprofile
2. Change in LDL cholesterol [ Time Frame: Baseline and 14 weeks ]
   LDL cholesterol (mg/dl)
3. Change in HDL cholesterol [ Time Frame: Baseline and 14 weeks ]
   HDL cholesterol (mg/dl)
4. Change in Triglycerides [ Time Frame: Baseline and 14 weeks ]
   Triglycerides (mg/dl)
5. Change in body composition by DXA [ Time Frame: Baseline and 14 weeks ]
   Lower abdominal fat mass as assessed by dual-energy X-ray absorptiometry (DXA).
6. Change in hs-CRP [ Time Frame: Baseline and 14 weeks ]
   High sensitivity C-reactive protein (mg/L)

Other Outcome Measures:

1. Change in mitochondrial structure and gene expression in skeletal muscle [ Time Frame: Baseline and 14 weeks ]
   Mitochondrial structure and gene expression in skeletal muscle as assessed by skeletal muscle biopsies.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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).

Contacts and Locations

Contacts

Contact: David Van, BS; 858-246-2342; ucsdresearchcoordinator@gmail.com

Contact: Victoria Green, BS; 858-246-2046

Locations

United States, California

Altman Clinical and Translational Research Institute; Recruiting

La Jolla, California, United States, 92093

Contact: Aryana Pazargadi, BS 858-246-2406

Principal Investigator: Pam Taub, MD

Sponsors and Collaborators

University of California, San Diego

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Salk Institute for Biological Studies

Investigators

• Principal Investigator: Pam Taub, MD; Associate Professor of Medicine

More Information

• Responsible Party: Pam Taub, MD, Associate Professor of Medicine, University of California, San Diego
• ClinicalTrials.gov Identifier: NCT04057339
• Other Study ID Numbers: 181088; 1R01DK118278-01 ( U.S. NIH Grant/Contract )
• First Posted: August 15, 2019
• Last Update Posted: January 3, 2022
• Last Verified: December 2021

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

Keywords provided by Pam Taub, MD, University of California, San Diego:

Time Restricted Eating; Circadian Rhythm; Glucose Homeostasis; Mitochondrial Function; Fasting

Additional relevant MeSH terms:

Metabolic Syndrome; Prediabetic State; Syndrome; Disease; Pathologic Processes; Insulin Resistance; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Diabetes Mellitus; Endocrine System Diseases