Time-Restricted Feeding (TRIO)

The Impact of Time-Restricted Feeding on Metabolism and Inflammation in Obesity (TRIO Study)

We propose to conduct a randomized 6-day isocaloric crossover feeding study in humans with prediabetes and obesity. We will study the effect of restricting the timing of caloric intake to earlier in the day (TRF) versus later in the day (usual feeding pattern, UFP) on glycemia and inflammation in an inpatient setting.

Study Overview

• Status: Completed
• Conditions: Obesity; Ketosis; Time Restricted Feeding; Inflammatory Markers; Glycemic Variation
• Intervention / Treatment: Other: Time restricted feeding arm; Other: usual feeding pattern arm

Detailed Description

Time Restricted Feeding (TRF) is a variant of intermittent fasting that confines caloric intake to active daytime hours and involves fasting for 12 to 14 hours. Circadian misalignment caused by changes in sleeping and eating behaviors has emerged as having a detrimental impact on weight, glucose homeostasis and other cardiovascular disease-related outcomes. Feeding during active periods appears to be advantageous for weight, glucose metabolism and lipid profiles whereas feeding during the inactive period confers deleterious effects on these outcomes. Therefore, TRF shows great promise as a novel intervention for addressing obesity and related cardiovascular outcomes.

Animal studies suggest that timing of feeding, including intermittent fasting or TRF, decreases inflammation and causes ketosis. Human studies that examined time restricted feeding for improvement in glycemia in as little as 4 days did not observe changes in clinical markers of inflammarion such as hsCRP. Moreover, systemic and adipose tissue inflammation as it occurs in obesity shows dynamic changes in the context of weight loss that would not be clearly apparent in a weight stable state. A potential mechanistic link between glycemic improvement and systemic inflammation would be the Receptor for Advanced Glycation End-Products (RAGE) and its soluble form (sRAGE).This form of inflammation has not been measured in reported eTRF studies and its relationship with eTRFwould bea significant contribution from the proposed study.

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10065
      • The Rockefeller University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. BMI >25 kg/m2
2. If taking probiotics during screening, must agree to continue taking them at the same dosage and frequency
3. HbA1C 5.7-6.4%
4. Willing to eat only the food provided
5. Willing to follow the feeding schedule, including fasting for 14 hours/day for 7 days
6. Willing to remain on the RU inpatient 24/7 unit except for weekend passes
7. Normally sleep between the hours of 10 pm and 8 am
8. Weight stable over the last 3 months defined as no more than a 5% change

Exclusion Criteria:

1. Diabetes
2. Any intermittent feeding diet within the last 2 weeks
3. HIV positive
4. Hepatitis
5. Self-reported autoimmune diseases (rheumatoid arthritis, SLE (lupus), Crohn's
6. Disease, psoriasis, etc.)
7. Current use of metformin
8. Smoked tobacco within the last 8 weeks
9. Taking any weight loss medication
10. Current use of systemic steroids
11. Allergic to adhesive tape
12. Taking clinically useful medications that contribute to significant weight loss or weight gain ie tricyclic antidepressants, some SSRIs, lithium, antipsychotics, some anticonvulsants, steroids, beta blockers, some antihistamines.
13. Currently pregnant
14. Any medical, psychological or social condition that, in the opinion of the Investigator, would jeopardize the health or well-being of the participant during any study procedures or the integrity of the data

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Timed restricted feeding; Time restricted feeding then usual feeding pattern Day 1, testing Day 2-7 all meals will be consumed as follows: 80% of calories consumed before 2 PM with remaining 20% consumed by 4PM. Fasting except for water, non caloric drinks for 14-16 hours Same number of calories consumed as in usual feeding pattern arm. Day 8 testing. Day 9-14 crossover to usual feeding pattern arm (meals consumed ad lib with 50% of calories consumed after 4 PM) for 6 days.	Other: Time restricted feeding arm; 80% of calories consumed before 2PM, remaining 20% consumed by 4PM. Fasting for 14-16 hours; Other: usual feeding pattern arm; All meals consumed ad lib with 50% of calories consumed after 4PM
Experimental: Usual feeding pattern; Usual feeding pattern, then time restricted feeding Day 1 testing Day 2-7 all meals will be consumed as follows: Meals consumed ad lib with 50% of calories consumed after 4 PM. Day 8 testing. Day 9-14 crossover to time restricted feeding arm with all meals consumed as follows: 80% of calories consumed before 2 PM with remaining 20% consumed by 4PM. Fasting except for water, non caloric drinks for 14-16 hours Same number of calories consumed as in usual feeding pattern arm for 6 days.	Other: Time restricted feeding arm; 80% of calories consumed before 2PM, remaining 20% consumed by 4PM. Fasting for 14-16 hours; Other: usual feeding pattern arm; All meals consumed ad lib with 50% of calories consumed after 4PM

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change in glycemic variation by mean amplitude of glycemic excursion (MAGE)	Day 2-Day14
Change in inflammatory marker concentrations (sRAGE and hsCRP) relative to the UFP arm	Day 2-Day 14

Secondary Outcome Measures

Outcome Measure	Time Frame
Shift from glucogenic to ketogenic metabolism in the TRF arm relative to the UFP arm by plasma metabolomics	Day 2- Day 14
Change in biological indices of appetite (incretins) in TRF arm relative to UFP arm.	Day 2 - Day 14
Changes in WBC transcriptomic profiles versus UFP arm between1, 7 and 14 days.	Day 2 - Day 14
changes in gut mirobiome profiles in the TRFarm	Day 2 - Day 14

Collaborators and Investigators

• Sponsor: Rockefeller University

Study record dates

Study Major Dates

• Study Start (Actual): June 10, 2021
• Primary Completion (Actual): August 15, 2022
• Study Completion (Actual): August 15, 2022

Study Registration Dates

• First Submitted: May 7, 2021
• First Submitted That Met QC Criteria: May 7, 2021
• First Posted (Actual): May 13, 2021

Study Record Updates

• Last Update Posted (Actual): August 24, 2022
• Last Update Submitted That Met QC Criteria: August 23, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Overnutrition; Nutrition Disorders; Overweight; Body Weight; Obesity
• Other Study ID Numbers: JAL-1007

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No