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

Obesity Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04259632
• Other study ID #: MED-2019-28331
• Secondary ID: R01DK124484
• Status: Completed
• Phase: N/A
• Start date: October 15, 2020
• Est. completion date: October 31, 2023

Study information

• Verified date: June 2024
• Source: University of Minnesota
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 115
• Est. completion date: October 31, 2023
• Est. primary completion date: October 31, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Obesity

Intervention

Behavioral:
• Time Restricted Eating (TRE)
daily eating window restricted to 8 hours
• Caloric Restriction (CR)
15% daily caloric deficient

Locations

Country	Name	City	State
United States	University of Minnesota	Minneapolis	Minnesota

Sponsors (2)

Lead Sponsor	Collaborator
University of Minnesota	National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Weight	Weight will be measured by standard scale and reported in kilograms.	Baseline, 12 weeks
Secondary	Change in Whole Body Percent Fat	Body composition will be measured by dual energy x-ray absorptometry (DXA). Parameters of body composition will be calculated by integrated DXA software. Whole body percent fat will be reported as a percentage.	Baseline, 12 weeks
Secondary	Change in Visceral Fat	Body composition will be measured by dual energy x-ray absorptometry (DXA). Parameters of body composition will be calculated by integrated DXA software. Visceral fat will be reported in grams.	Baseline, 12 weeks
Secondary	Change in Lean Mass	Body composition will be measured by dual energy x-ray absorptometry (DXA). Parameters of body composition will be calculated by integrated DXA software. Lean mass will be reported in kilograms.	Baseline, 12 weeks
Secondary	Change in Fat Mass	Body composition will be measured by dual energy x-ray absorptometry (DXA). Parameters of body composition will be calculated by integrated DXA software. Fat mass will be reported in kilograms.	Baseline, 12 weeks
Secondary	Change in Caloric Intake	Two interviewer-administered 24-hour dietary recalls will be collected from each participant at baseline and 12 weeks. The recalls will be conducted over the telephone and will be unannounced to minimize measurement reactivity. Diet data will be collected using the Nutrition Data System for Research (NDSR) to calculate Calories. Calories will be averaged across the 2 recalls at each time point. Outcome will be reported as difference between average caloric intake at baseline and 12 weeks. Outcome will be reported in kilocalories (Calories).	Baseline, 12 weeks
Secondary	Change in metabolic flexibility	indirect calorimetry to measure glucose and fat oxidation for ~ 30 minutes before and at the end of the 2 step 4-hour hyperinsulinemic-euglycemic clamp [low-dose (10 mU/m2/min) insulin infusion for 2 hours, high-dose (40 mU/m2/min) insulin infusion for 2 hours] Fluctuations in VO2 and VCO2 in the first 5-10 minutes of data acquisition were removed and the mean VO2 and VCO2 at steady state was used for data analysis. The respiratory exchange ratio (RER) was calculated by VCO2 / VO2. . Metabolic flexibility was calculated by the RERclamp-RERrest	baseline, 12 weeks