Prolonged Daily Fasting as a Viable Alternative to Caloric Restriction in At-Risk Obese Humans

NCT ID: NCT04259632

Last Updated: 2025-12-30

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: NA
• Total Enrollment: 115 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-10-15
• Study Completion Date: 2026-03-31

Brief Summary

Purpose: Obesity is reaching epidemic proportions, affecting 36% of the adult population in the United States. There is intense interest in dietary management to treat obesity and its associated complications. The first line of obesity treatment is caloric restriction (CR), although recidivism is common. For moderate CR, attrition rates of 20% are often reported, therefore weight loss options beyond CR are urgently needed.

Detailed Description

Aim#1: Evaluate the effect of TRE with ad libitum intake on weight and body composition.

H 1.1: Individuals in the TRE and CR groups will have similar weight loss, which will be greater than weight loss achieved in the non-TRE group (primary outcome).

H 1.2: TRE will result in greater loss of loss of total body fat (quantified by DXA) and greater loss of hepatic/visceral fat/ectopic fat (quantified by MRI) than CR.

Aim#2: Assess the effect of TRE with ad libitum intake on caloric balance. H 2.1: TRE will reduce caloric intake compared with non-TRE [gold-standard interviewer administered 24-hour dietary recall (primary outcome)] with similar reduction as with CR, H.2.2: Compared with non-TRE, TRE will result in selection of more nutrient dense foods during a supervised meal within their eating window; this selection will be similar to CR. H 2.3 TRE will not alter physical activity, but will increase fat oxidation compared with CR and non-TRE.

Aim#3: Assess the effect of TRE with ad libitum intake on metabolic flexibility.

H 3.1: TRE will enhance metabolic flexibility compared with CR and non-TRE as measured by indirect calorimetry [RQ:Respiratory quotient before and during 2 step 6,6-2H2 hyperinsulinemic-euglycemic clamp: primary outcome].

H 3.2: TRE will improve insulin sensitivity compared with non-TRE and similar to CR.

H 3.3: TRE will augment greater fasting lipolysis compared to CR and non-TRE as measured by [U-13C] palmitate and enhance lipolysis suppression during the 2 step 6,6-2H2 hyperinsulinemic-euglycemic clamp.

If these hypotheses are confirmed, this project has significant impact. First, it will advance understanding of the mechanisms underpinning this innovative intervention. Second, TRE can be a practical means of implementing prolonged fasting on a large scale, thereby transforming the treatment of obesity.

Research reported in this publication was supported by the National Center for Advancing Translational Sciences of the National Institutes of Health Award Number UL1-TR002494. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Conditions

Obesity

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Time Restricted Eating (TRE)

For the TRE group, we will restrict the eating window to 8 hours, where they will eat ad libitum. This is the same interval established by Dr. Panda and by our preliminary data. This interval will be entered into the mCC app and participants will be asked to adhere to this eating window during the intervention. All eating occasions will be logged using the mCC app. Only water and medications will be allowed outside of the eating window.

Group Type: EXPERIMENTAL

Time Restricted Eating (TRE)

Intervention Type: BEHAVIORAL

daily eating window restricted to 8 hours

Caloric Restriction (CR)

Participants randomized to CR will meet with the study dietitian prior to the intervention and be counseled on options to reduce their caloric intake by 15%, while maintaining their eating window. The 15% reduction was selected as our preliminary data and recent literature suggest that TRE with ad libitum intake reduces caloric intake by \~270 to 300 cal/day. The 15% CR is similar to the 11.9% CR achieved by the CALERIE-2 study, which is a 2 year study of CR.26 All eating occasions will be logged using the mCC app. The weekly dietitian review of the mCC information will include maintenance of the eating window and examination of dietary intake to determine compliance with the 15% CR.

Group Type: ACTIVE_COMPARATOR

Caloric Restriction (CR)

Intervention Type: BEHAVIORAL

15% daily caloric deficient

Unrestricted Eating (non-TRE)

For the unrestricted eating (non-TRE) group, participants will eat ad libitum per their usual habits. They will receive initial counseling about mCC logging. All eating occasions will be logged using the mCC app.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Time Restricted Eating (TRE)

daily eating window restricted to 8 hours

Intervention Type: BEHAVIORAL

Caloric Restriction (CR)

15% daily caloric deficient

Intervention Type: BEHAVIORAL

Eligibility Criteria

Inclusion Criteria

• BMI ≥30 and ≤ 55 kg/m^2
• Own a smartphone compatible with the myCircadianClock (mCC) phone application
• Self-reported habitual wakening between 5-9 am
• Self reported sleep duration of 6-9 hours
• Weight must be stable [+/- 5 pounds] for at least 3 months prior to the study
• Eating window (time between 1st food intake and last food take) ≥14 hours using mCC
• Insulin resistance based on HOMA-IR≥ 2.5 from screening visit results
• Able to understand English

Exclusion Criteria

• Use of beta-blockers or medications known to affect weight, such as thiazolidinedione (TZD), insulin, glucagon-like peptide (GLP)-1 agonists, phentermine, or sibutamine
• Shift work (i.e. working from 11pm to 7am)
• Clinically significant medical issues (diabetes, cardiovascular disease, uncontrolled pulmonary disease)
• A history of abnormal laboratory results, such as hematologic (platelets < 100), hepatic (LFTs > 2X nl), renal (Cr > 1.5)
• MRI contraindication (metal in body, claustrophobia)
• Eating window < 12 hours per day
• Unable to consistently document food intake using the mCC app (need at least 2 eating occasions> 6 hours apart on a given day for at least 50% of days)
• Pregnancy
• Illiteracy
• Concern for active eating disorder per screening questionnaire
• Self-reported eating disorder or history of eating disorder

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

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

NIH

Sponsor Role: collaborator

University of Minnesota

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

University of Minnesota

Minneapolis, Minnesota, United States

Countries

United States

References

Chen DA, Pena RH, Oldenburg N, Wang Q, Helgeson E, Yentzer B, Taddese A, LaPage N, Manoogian ENC, Panda S, Chow LS. Post-intervention sustainability of time-restricted eating versus caloric restriction: a secondary analysis. Int J Obes (Lond). 2025 Nov 28. doi: 10.1038/s41366-025-01968-2. Online ahead of print.

Reference Type: DERIVED

PMID: 41315749 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

R01DK124484

Identifier Type: NIH

Identifier Source: secondary_id

View Link

MED-2019-28331

Identifier Type: -

Identifier Source: org_study_id