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

Not Applicable

Active, not recruiting

Conditions: Obesity

Registration Number: NCT04259632

Lead Sponsor: University of Minnesota

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.

Recruitment & Eligibility

Status: ACTIVE_NOT_RECRUITING

Sex: All

Target Recruitment: 88

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
Change in Weight	12 weeks	Weight will be measured by standard scale and reported in kilograms. This between 2 time points - baseline and 12 weeks

Secondary Outcome Measures

Name	Time	Method
Change in Whole Body Percent Fat	Baseline, 12 weeks	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.
Change in Visceral Fat	Baseline, 12 weeks	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.
Change in Lean Mass	Baseline, 12 weeks	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.
Change in Fat Mass	Baseline, 12 weeks	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.
Change in Caloric Intake	Baseline, 12 weeks	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).
Change in Metabolic Flexibility	baseline, 12 weeks	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