NCT03411356.

Study name	Intermittent fasting versus daily caloric restriction for weight loss
Methods	Randomised controlled trial
Participants	150 participants Ages Eligible for Study: 18 years to 55 years (adult) Sexes Eligible for Study: all Accepts Healthy volunteers: yes Inclusion Criteria Female or Male Age 18‐55 years Body Mass Index 27‐46 kg/m2 Sedentary: defined as <150 minutes per week of voluntary exercise at moderate intensity or greater and < 60 minutes per day of total habitual physical activity (i.e. work‐related, transportation‐related) at moderate intensity or greater, over the past 3 months. No self‐report of acute or chronic disease (CVD, diabetes, gastrointestinal disorders and orthopedic problems in particular) No plans to relocate within the next 12 months No plans for extended travel (> 2 weeks) within the next 12 months No nicotine use Live or work within 30 minutes of the Anschutz Health and Wellness Center (AHWC) (exceptions may be made at the discretion of the Study PI on a case by case basis for highly‐motivated people). Capable and willing to give informed consent, understand exclusion criteria, and accept the randomised group assignment. Have a primary care physician (or are willing to establish care with a primary care physician prior to study enrolment) to address medical issues which may arise during screening or study procedures/interventions. For Females Not currently pregnant or lactating Not pregnant within the past 6 months Not planning to become pregnant in the next 12 months Sexually active women of childbearing potential may be enrolled if they have had a tubal ligation or use a reliable means of contraception
Interventions	Arm Intervention/treatment Active Comparator: Daily Caloric Restriction (DCR) Participants in this group will focus on daily calorie restriction as their dietary weight loss strategy. Behavioural: Daily Caloric Restriction (DCR) Participants in this group will be given a calorie goal designed to produce a 34.3% energy deficit from estimated baseline weight maintenance energy requirements. Participants in this group will also receive a 12‐month comprehensive group‐based behavioural weight loss program and will be instructed in specific strategies to support DCR. Randomized groups will meet separately. Participants in this group will also be asked to increase moderate intensity physical activity to a target of 300 minutes per week. Experimental: Intermittent Fasting (IMF) Participants in this group will focus on modified intermittent fasting as their dietary weight loss strategy. Behavioural: Intermittent Fasting (IMF) Participants in this group will be instructed to limit energy intake to 20% of estimated baseline energy requirements on three non‐consecutive days per week, and to eat ad libitum the other 4 days per week. Participants in this group will also receive a 12‐month comprehensive group based behavioural weight loss program and will be instructed in specific strategies to support IMF. Randomised groups will meet separately. Participants in this group will also be asked to increase moderate intensity physical activity to a target of 300 minutes per week.
Outcomes	Primary outcome measures: Change in Body Weight [ Time Frame: Baseline and weeks 4, 13, 26, 39, and 52. ] Body weight will be measured via clinic scale. Secondary Outcome Measures: Changes in Body Composition [ Time Frame: Baseline and weeks 26, and 52. ] Body composition will be assessed with dual‐energy x‐ray absorptiometry (DXA). Changes in Blood Pressure [ Time Frame: Baseline and weeks 13, 26, and 52. ] Blood pressure will be measured with a sphygmomanometer. Changes in Fasting Lipids [ Time Frame: Baseline and weeks 26 and 52 ] 12 hour fasting blood sample for measurement of lipid profile. Changes in Insulin Sensitivity [ Time Frame: Baseline and weeks 26 and 52 ] 12 hour fasting blood sample for measurement of insulin and glucose. Insulin sensitivity (homeostasis model assessment of insulin resistance [HOMA‐IR]) will be calculated as ([insulin] x [fasting glucose x 0.055]/22.5). Changes in Objectively Measured Energy Intake (EI) [ Time Frame: Baseline, weeks 26 and 52 ] EI will be measured using the doubly‐labelled water (DLW) intake‐balance method. Changes in Self‐Reported Energy Intake (EI) [ Time Frame: Baseline and weeks 13, 26, and 52. ] Dietary energy intake (kcals/day) will be measured with diet diaries. Changes in Self‐reported Diet Composition [ Time Frame: Baseline and weeks 13, 26, and 52. ] Dietary macronutrient intake will be measured with diet diaries. Changes in Self‐Reported Dietary Adherence [ Time Frame: Weeks 4, 8, 13, 18, 22, 26, 30, 34, 39, 44, 48, 52 ] Adherence to prescribed diet will be assessed with a monthly questionnaire. Changes in Resting Energy Expenditure (REE) [ Time Frame: Baseline and weeks 26, and 52. ] REE will be measured using indirect calorimetry. Changes in Total Daily Energy Expenditure (TDEE) [ Time Frame: Baseline and weeks 26, and 52. ] TDEE will be measured using the doubly‐labelled water (DLW) method. Changes in Physical Activity [ Time Frame: Baseline and weeks 13, 26, and 52. ] Physical activity will be measured with activity monitors. Changes in Sedentary Behaviour [ Time Frame: Baseline and weeks 13, 26, and 52 ] Sedentary behaviour will be measured with activity monitors. Other Outcome Measures: Changes in Waist Circumference [ Time Frame: Baseline and weeks 13, 26, and 52 ] Waist circumference will be measured with a tape measure just over the iliac crest Changes in Highly Sensitive C Reactive Protein (hs CRP) [ Time Frame: Baseline and weeks 26 and 52 ] 12 hour fasting blood sample fro measurement of hs CRP Changes in Leptin [ Time Frame: Baseline and weeks 26 and 52 ] 12 hour fasting blood sample for measurement of Leptin Changes in Ghrelin [ Time Frame: Baseline and weeks 26, and 52 ] 12 hour fasting blood sample for measurement of Ghrelin Changes in Brain‐Derived Neurotrophic Factor (BDNF) [ Time Frame: Baseline and weeks 26 and 52 ] 12 hour fasting blood sample for measurement of BDNF Predictors of Weight Loss [ Time Frame: Baseline and weeks 13, 26, 52, and 78 ] Predictors of weight loss will be assessed in both groups with questionnaires periodically over the 52 week intervention Difficulty of Test Fast [ Time Frame: Baseline ] Participants will be asked to perform a test fast i.e. to limit intake to 25% of estimated baseline energy requirements for 1 day at baseline (prior to randomisation and beginning the interventions). Difficulty of the test fast will be assessed using a 1‐10 Likert scale with 1 representing no difficulty and 10 representing extreme difficulty. Intervention Preference [ Time Frame: Baseline ] Intervention preference will be assessed by asking participants which intervention group (IMF or DCR) they would prefer at baseline (prior to randomisation) 6 Month Post‐Intervention Follow‐Up Body Weight [ Time Frame: 26 weeks after completion of the 52‐week intervention (i.e. at week 78) ] Body weight will be measured via clinic scale. 6 Month Post‐Intervention Follow‐Up Body Composition [ Time Frame: 26 weeks after completion of the 52‐week intervention (i.e. at week 78) ] Body composition will be assessed with dual‐energy x‐ray absorptiometry (DXA). Evaluation of Genotype as Predictor of Weight Loss [ Time Frame: Baseline ] DNA will be isolated from a whole blood sample. DNA genotyping will be performed using a commercial array which covers > 2 million single nucleotide polymorphisms across the human genome. Changes in DNA Methylation [ Time Frame: Baseline and weeks 13, 26 and 52 ] DNA will be isolated from whole blood samples. DNA genotyping will be performed using a commercial array which covers > 2 million single nucleotide polymorphisms across the human genome. DNA methylation will be assessed using commercial arrays which covers >850,000 methylation sites across the human genome. Changes in Stool Microbiome [ Time Frame: Baseline and weeks 13, 26, and 52 ] Stool samples will be collected to evaluate types and relative quantities of bacteria in fecal specimens Changes in Reproductive Hormones [ Time Frame: Over one menstrual cycle at baseline, over the first 3 menstrual cycles after starting the 52 week intervention and over one menstrual cycle after completing the 52 week intervention. ] Daily urine collection over a menstrual cycle in subset of pre‐menopausal women Changes in Peptide YY [ Time Frame: Baseline and weeks 26 and 52 ] 12 hour fasting blood sample for measurement of Peptide YY Changes in Hemoglobin A1C [ Time Frame: Baseline and weeks 26 and 52 ] 12 hour fasting blood sample for measurement of Hemoglobin A1C
Starting date	December 22, 2017
Contact information	Victoria Catenacci, MD
Notes	NCT03411356