Ketogenic Diets for Weight Loss Maintenance: Impact on Energy Expenditure and Appetite in Individuals With Obesity (KETOWEI)

The goal of this clinical trial is to investigate whether a Ketogenic Diet (KD) can increase Total Energy Expenditure (TEE), while benefiting appetite, during weight loss maintenance in reduced-obese individuals.

Study Overview

• Status: Recruiting
• Conditions: Obesity
• Intervention / Treatment: Behavioral: Calorie Restriction; Behavioral: Behavioral Support; Behavioral: Diet Therapy; Behavioral: Diet Therapy

Detailed Description

The total duration of the intervention will be 10 weeks. Participants will first undergo 4 weeks of a low-energy diet (LED), aiming to induce a minimum of 5% weight loss (weight loss phase). Those who achieve at least a 5% weight loss will then be randomized (1:1) to a 6-week weight loss maintenance (WLM) diet, either a KD or an isocaloric low-fat diet, with the first 2 weeks being a gradual refeeding.

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Catia Martins, PhD; Phone Number: 205-934-7922; Email: catia197@uab.edu

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • Recruiting
      • University of Alabama at Birmingham
      • Contact: Catia Martins, PhD; Phone Number: 2059347922; Email: catia197@uab.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• BMI 30-45 kg/m2
• Both men and women
• Age between 18-65 years
• Sedentary to moderately active (<2 h/wk of moderate, structured, intentional, exercise)

Exclusion Criteria:

• Pregnancy or lactation
• Daily use of tobacco (>1 pk/wk)
• Change in weight greater than 5 lb in the previous 3 months
• Cognitive impairment
• Previous bariatric surgery
• History of eating disorder
• Presence of any condition (e.g. DM2, PCOS, inflammatory disease, untreated thyroid disease, fluid overload states such as chronic kidney disease, congestive heart failure, or cirrhosis)
• Use of any medication (e.g., glucocorticoid, GLP-1 analogues, hormone replacement therapy) deemed to interfere with study outcomes.
• Pre-menopausal women will need to have a regular menstrual cycle (28+/-2 days) or be on hormonal contraceptives
• Fasting glucose plasma concentration >125 mg/dl and/or HbA1c > 6.4%

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ketogenic Diet; Participants randomized to the ketogenic diet will follow a diet with 5% energy from carbohydrates, 70% from fat, and 25% from protein for 6 weeks. The first 2 of the 6 weeks weeks will be a gradual refeeding, with participants slowly withdrawing from the meal replacements used during the 4-week weight loss phase, while introducing more food.	Behavioral: Calorie Restriction; Participants will follow a commercial low-energy diet and be provided with meal replacements for 4 weeks aiming to achieve a minimum of 5% weight loss.; Behavioral: Behavioral Support; Participants will meet weekly with a registered dietitian, for a 20-minute consultation throughout the entire study period (10 weeks) to increase engagement and improve adherence and retention.; Behavioral: Diet Therapy; Participants will be provided food to meet the ketogenic diet prescription for the 6-week weight maintenance phase.; Behavioral: Diet Therapy; Participants will have food provided to meet the standard low-fat diet prescription for the 6-week weight maintenance phase.
Active Comparator: Low-Fat Diet; Participants randomized to the low-fat diet will follow a diet with 50% energy from carbohydrates, 25% energy from fat, and 25% energy from protein for 6 weeks. The first 2 of the 6 weeks weeks will be a gradual refeeding, with participants slowly withdrawing from the meal replacements used during the 4-week weight loss phase, while introducing more food.	Behavioral: Calorie Restriction; Participants will follow a commercial low-energy diet and be provided with meal replacements for 4 weeks aiming to achieve a minimum of 5% weight loss.; Behavioral: Behavioral Support; Participants will meet weekly with a registered dietitian, for a 20-minute consultation throughout the entire study period (10 weeks) to increase engagement and improve adherence and retention.; Behavioral: Diet Therapy; Participants will be provided food to meet the ketogenic diet prescription for the 6-week weight maintenance phase.; Behavioral: Diet Therapy; Participants will have food provided to meet the standard low-fat diet prescription for the 6-week weight maintenance phase.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline total energy expenditure	Total Energy Expenditure (TEE) refers to the total amount of energy (calories) your body uses in a day. Twenty-four-hour EE and RQ will be measured inside the whole room indirect calorimeter (chamber) following standard procedures	Baseline, week 6, week 10

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in appetite ratings	Subjective appetite ratings are personal feelings or perceptions about hunger, fullness, desire to eat (DTE), and prospective food consumption (PFC) usually measured using self-reported scales ranging from "not at all" to "extremely". Subjective appetite ratings (hunger, fullness, DTE and PFC) will be measured using a validated 10cm visual analog scale which will be given to the participants inside the chamber before meals.	Baseline, week 6, week 10
Change in total body composition	Bioimpedance analysis (BIA) will be used to measure fat mass, fat-free mass, total, extra, and intra-cellular water.	Baseline, week 4, week 6, week 10
Change in total body composition	FM, bone mass, and lean body mass will be determined by dual-energy X-ray absorptiometry (iDXA instrument, GE Healthcare Lunar, Madison, WI) with the use of software version 1.5g (Lunar Corp).	Baseline, week 4, week 6, week10
Change in total body weight	Body weight is the total amount a person weighs when measured on a scale.	Baseline, week 4, week 6, week 10
Change in resting energy expenditure	Resting Energy Expenditure (REE) is the amount of energy (calories) your body needs to keep working while you're at rest. Participants will enter the chamber in the morning in the fasting state. REE will be measured while the participant is in the metabolic chamber.	Baseline, week 6, week 10
Change in mechanical efficiency	Walking economy will be assessed using a submaximal treadmill test, performed 90 minutes after breakfast. Following a familiarization period, participant will walk on the treadmill at 2 miles/hour for 15 minutes, followed by another 15 minutes at 2.5 miles/hour.	Baseline, week 6, week 10
Change in fasting insulin	Circulating (serum) fasting insulin will be measured using validated methods	Baseline, week 6, week 10
Change in fasting cholecystokinin	Circulating (plasma) fasting cholecystokinin will be measured by RIA.	Baseline, week 6, week 10
Change in fasting ghrelin	Circulating (plasma) fasting ghrelin concentrations will be measured by ELISA	Baseline, week 6, week 10
Change in fasting glucagon-like peptide-1	Circulating (plasma) fasting total GLP-1 will be measured by ELISA	Baseline, week 6, week 10
Change in fasting peptide YY (PYY)	Circulating (plasma) fasting PYY3-36 concentrations will be measured by ELISA	Baseline, week 6, week 10
Change in postprandial insulin	Circulating (serum) insulin measured before and 30, 60, 90, and 120 minutes after intake of breakfast with validated methods	Baseline, week 6, week 10
Change in postprandial cholecystokinin	Circulating (plasma) cholecystokinin measured before and 30, 60, 90, and 120 minutes after intake of breakfast with RIA.	Baseline, week 6, week 10
Change in postprandial ghrelin	Circulating (plasma) ghrelin measured before and 30, 60, 90, and 120 minutes after intake of breakfast with ELISA	Baseline, week 6, week 10
Change in postprandial glucagon-like peptide-1	Circulating (plasma) total GLP-1 measured before and 30, 60, 90, and 120 minutes after intake of breakfast by ELISA	Baseline, week 6, week 10
Change in postprandial peptide yy	Circulating (plasma) PYY3-36 concentrations measured before and 30, 60, 90, and 120 minutes after intake of breakfast with ELISA	Baseline, week 6, week 10

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Blood work: beta hydroxybutyrate	Adherence to the dietary interventions will be assessed using objective biochemical analysis through the measurement of beta hydroxybutyrate in blood using a ketone meter.	Week 1, week 2, week 3, week 4, week 5, week 6, week 7, week 8, week 9, week 10
Urine sample: acetoacetate	Adherence to the dietary interventions will be assessed using objective biochemical analysis through the measurement of acetoacetate in urine using Ketostix reagent strips.	Week 1, week 2, week 3, week 4, week 5, week 6, week 7, week 8, week 9, week 10
Change in glucose	The fasting blood sample collected before the participants enter the chamber will be analyzed for circulating glucose using the SIRRUS analyzer.	Baseline, week 6, week 10
Change in total cholesterol	The fasting blood sample collected before the participants enter the chamber will be analyzed for circulating total cholesterol concentrations using the SIRRUS analyzer.	Baseline, week 6, week 10
Change in high-density lipoprotein cholesterol	The fasting blood sample collected before the participants enter the chamber will be analyzed for circulating HDL-C using the SIRRUS analyzer.	Baseline, week 6, week 10
Change in triglycerides	The fasting blood sample collected before the participants enter the chamber will be analyzed for circulating triglyceride concentrations using the SIRRUS analyzer.	Baseline, week 6, week 10
Change in free fatty acids	The fasting blood sample collected before the participants enter the chamber will be analyzed for circulating free fatty acid concentrations using the SIRRUS analyzer.	Baseline, week 6, week 10
Change in average appetite	Participants will be asked to report their average hunger, fullness, desire to eat and prospective food consumption (e.g. how hungry did you feel this week? how much did you think about food this week?) over the previous week using a 10-cm visual analogue scale ranging from "not at all" to "extremely".	Baseline, week 1, week 2, week 3, week 4, week 5, week 6, week 7, week 8, week 9, week 10

Collaborators and Investigators

• Sponsor: University of Alabama at Birmingham
• Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2025
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): March 30, 2027

Study Registration Dates

• First Submitted: December 10, 2024
• First Submitted That Met QC Criteria: December 13, 2024
• First Posted (Actual): December 16, 2024

Study Record Updates

• Last Update Posted (Actual): April 7, 2026
• Last Update Submitted That Met QC Criteria: April 3, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Energy expenditure; Weight loss; Ketogenic Diet; Appetite; Weight loss maintenance
• Additional Relevant MeSH Terms: Nutrition Disorders; Overnutrition; Body Weight; Body Weight Changes; Overweight; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Signs and Symptoms; Obesity; Weight Loss; Therapeutics; Diet, Food, and Nutrition; Physiological Phenomena; Nutritional Physiological Phenomena; Psychotherapy; Behavioral Disciplines and Activities; Nutrition Therapy; Diet; Energy Intake; Diet Therapy; Behavior Therapy; Caloric Restriction
• Other Study ID Numbers: IRB-300012956; P30DK079626 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: This project will produce demographic information, anthropometric and body composition data, energy expenditure, fat oxidation, plasma concentrations of several gastrointestinal hormones involved in appetite regulation, insulin, glucose, blood lipids, and subjective appetite feelings. Data will be obtained from bioimpedance analysis and dual-energy x-ray absorptiometry (DEXA) for body compsoiiton; ELISA, RIA and other laboratorial methods used for the quantification of hormones and metabolites, and questionnaires and visual analogue scales. Data will be collected from 20 research participants. We estimate to be generating gigabyte (.csv) amounts of data. The methodology, statistical analysis plan, and a data dictionary will also be shared. Based on ethical considerations, scientific data will be de-identified and shared at the participant level. Data will be made available in .csv format and will not require the use of specialized tools to be accessed or manipulated.
• IPD Sharing Time Frame: The data will be shared with others by the time the related study is published and will stay available for at least 10 years.
• IPD Sharing Access Criteria: All datasets that can be shared will be deposited in the NIH-supported Vivli repository which specializes in clinical trial data. Given the sensitive nature of the dataset, de-identified human subjects' data will be made available in Vivli, which restricts access to the data to qualified investigators with an appropriate research question who sign a data use agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No