Evaluating Metabolic Health in Individuals With Extreme Obesity

Evaluating Energy Metabolism and Metabolic Health in Individuals With Extreme Obesity

This research will evaluate energy metabolism (expenditure and fat oxidation), metabolic flexibility (response to a high-fat test meal) in 10 individuals with a BMI ≥60 kgm2 using gold-standard assessments of energy metabolism, metabolic flexibility, and body composition. Males and females (18-80 y) with extreme obesity (BMI: ≥60 kg/m2) will be recruited from Baton Rouge, Louisiana. Exclusion criteria include major organ failure, uncontrolled endocrine disease, severe psychiatric illness, pregnancy, and inability to comply with study procedures. The total duration of participation for each individual is estimated at approximately 10 days. If qualified, participants (BMI≥60 kg/m2; n=10) will complete one outpatient visit and one inpatient visit with 36hr metabolic chamber testing.

Study Overview

• Status: Not yet recruiting
• Conditions: BMI>40
• Intervention / Treatment: Other: High-fat test meal

Detailed Description

For visit 1, Subjects will arrive at the outpatient clinic following an overnight fast (nothing to eat or drink, except water, for 10 hours) and the following tests will be performed: anthropometry, blood pressure, pulse rate, temperature, pregnancy test for women, collection of fasting and timed urine samples, fasting and timed blood draws, isotope dilution for sodium bromide, dual-energy X-ray absorptiometry, bioelectrical impedance analysis, ultrasound, accelerometer distribution, and completion of multiple questionnaires. Then, participants will wear the accelerometer and complete an ASA24 questionnaire from Visit 1 to Visit 2-D1, in which participants will return for the first metabolic chamber stay. For D3-Creatine assessment, participants will be instructed to collect an additional urine sample within 5-6 days of Visit 1 that will be dropped off when they arrive for their V2-D1 visit at Pennington Biomedical.

For Visit 2-D1, seven days after being dosed with DLW, subjects will arrive at the inpatient clinic following an overnight fast (nothing to eat or drink, except water, for at least 10 hours). The purpose of this visit is to collect urine samples for D3, DLW, remove the accelerometer, and complete the first overnight metabolic chamber visit, employing a high-fat test meal to assess metabolic flexibility. During this visit, the following tests will be performed: anthropometry, blood pressure, pulse rate, temperature, fasting urine sample, fasting blood draw, accelerometer removal, standardized breakfast and lunch, 13-h overnight stay in the metabolic chamber with a high-fat dinner, urine collection throughout the chamber stay, and VAS before and after lunch and dinner.

Lastly, for Visit 2-D2, upon completing the first overnight inpatient stay in the metabolic chamber (previous 13 hours), participants will exit the chamber at 0700 for one hour to allow for re-calibration of the chambers. Participants will be fasted since their high-fat dinner meal the previous night (approximately 11.5 hours) and will have their metabolic weight taken along with a fasting blood draw. They will then re-enter the metabolic chamber at 0800 and begin a 23-h chamber stay consisting of controlled meals throughout the stay. The purpose of this visit is to collect 23-h chamber data pertaining to various metrics of energy expenditure (e.g., BMR, RMR, TEF, SMR, etc.) and substrate oxidation (i.e., respiratory quotient). During this visit, the following tests will be performed: anthropometry, blood pressure, pulse rate, temperature, fasting blood draw, 23-h stay in the metabolic chamber with controlled meals, urine collection throughout the chamber stay, and VAS before and after lunch and dinner.

After completing of the second overnight chamber stay (Visit 2-D2), participants will exit the metabolic chamber and have their metabolic weight taken.

• Study Type: Observational
• Enrollment (Estimated): 10

Contacts and Locations

• Study Contact: Name: Eric Ravussin, PhD; Phone Number: 2257633186; Email: Eric.Ravussin@pbrc.edu
• Study Contact Backup: Name: Christian Rodriguez, PhD; Phone Number: 8062249114; Email: christian.rodriguez@pbrc.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

The population for this study is individuals aged 18 to 80 years old who have a BMI greater than or equal to 60 kg/m2 who are willing to consume pre-prepared meals and are willing to have biospecimens and images stored for future use. The reason for seeking to evaluate this specific population is because individuals with extreme obesity possess high surgical and comorbidity risks, but there is a very small amount of research conducted in these individuals.

Description

Inclusion Criteria:

• Healthy male or female
• Between 18 - 80 years of age
• BMI ≥60 kg/m2
• Willing to consume pre-prepared meals
• Willing to comply with the study procedures.
• Willing to have biospecimens and images stored for future use.

Exclusion Criteria:

• Diabetic individuals with complications such as:

  • Diabetic eye disease requiring laser treatment
  • Diabetic nerve disease associated with foot ulcers or amputations
  • Diabetic vascular disease associated with gangrene or amputation
  • Diabetic kidney disease accompanied by a creatinine greater than 2.0 mg/dL
  • Individuals with prior gastrointestinal surgery except appendectomy or cholecystectomy
• Individuals with untreated thyroid disease
• Individuals with untreated or poorly controlled binge eating disorder, bulimia, substance abuse or dependence, mania, and psychosis.
• Women who are pregnant, trying to become pregnant, or currently breastfeeding.
• Individuals with major organ system failure like cirrhosis, hepatic insufficiency, portal hypertension, severe renal insufficiency or on dialysis, severe arterial insufficiency, dementia or the inability to give an informed consent.
• Being unwilling to comply with the study procedures.
• Not willing to have biospecimens and/or images stored for future research use.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Metabolic Flexibility; Ten Males and females (18-80 y) with extreme obesity (BMI: ≥60 kg/m2) will complete one outpatient visit and one inpatient visit with 36 hours of metabolic chamber testing evaluate energy metabolism (expenditure and fat oxidation), metabolic flexibility (response to a high-fat test meal) using gold-standard assessments of energy metabolism, metabolic flexibility, and body composition.

Other: High-fat test meal; At Visit 2-D1, subjects will enter the chamber at approximately 17:30 and exit the following morning at 07:00. Energy expenditure, respiratory exchange ratio (RER), and 12-h oxidation of CHO, fat, and protein will be calculated per standard PBRC protocols. While in the chamber, participants will collect all their urine for measurement of urinary nitrogen. Subjects will be served one high-fat meal while they are in the chamber (40% of the daily energy requirements).; Other Names: metabolic flexibility

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
24-hour Energy Expenditure	24-hour energy expenditure will be assessed from participants spending 23 hours in a metabolic chamber.	Day 9
24-hour Fat Oxidation	This will be collected from the 23-hour chamber stay during Visit 2, Day 2. Specifically, this represents the total grams of fat oxidized over the 23-hour stay, calculated from indirect calorimetry stoichiometry.	Day 9
Basal Energy Expenditure	This represents the amount of energy expended under strict basal conditions: post-absorptive (typically 10-12h fasted), thermoneutral, fully awake but supine and motionless, no recent physical activity. This will be collected from the 23-hour metabolic chamber stay.	Day 9
Resting Energy Expenditure	This is the energy expended at rest but under less stringent conditions than basal: seated or supine, awake, post-absorptive but with less rigor about prior activity, temperature, and emotional state. This will be collected from the 23-hour metabolic chamber stay.	Day 9
Sleeping Metabolic Rate	This is the energy expenditure during sleep, typically computed from the lowest stable ~3-hour window between roughly 02:00 and 05:00 when arousal and movement are minimal. Per our Standard Operating Procedures, this will be computed between 01:00 and 05:00.	Day 9
Thermic Effect of Food	This represents the postprandial rise in energy expenditure above the pre-meal baseline, integrated over the period until energy expenditure returns to baseline (typically 4-6 hours for a mixed meal). This reflects the energy cost of digestion, absorption, and substrate processing, plus a sympathetic activation component.	Day 9
Spontaneous Physical Activity	This is the energy expended on non-volitional movement: fidgeting, postural adjustments, small spontaneous movements during otherwise sedentary periods in the chamber. It is commonly measured by radar/Doppler motion sensors and quantified either as a fraction of chamber time active (% activity) or as the energy cost of activity above sleeping metabolic rate.	Day 9
Free-living Total Daily Energy Expenditure	This is the gold-standard free-living EE measurement: participants drink a dose of ²H₂¹⁸O, and the differential elimination rates of the two isotopes over ~7-14 days yield CO₂ production and therefore EE under habitual living conditions. It captures everything the chamber misses: occupational and recreational activity, environmental temperature variation, real meal patterns.	Day 1 to Day 8

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Food Quotient	This is the amount of minutes from meal ingestion until RER first reaches (or crosses) the meal's FQ. This represents the speed of the switch of fuel oxidation rather than its endpoint. A flexible system gets there quickly; an inflexible one takes hours or never arrives.	Day 8
Respiratory Exchange Ratio: Food Quotient Ratio	This is the measured respiratory exchange ratio divided by the meal's food quotient (the theoretical RER if the meal were fully oxidized as ingested). A ratio of 1.0 means whole-body substrate oxidation has fully matched the macronutrient composition of what was just eaten; <1.0 means oxidation is lagging behind intake (fat-dominant fuel selection persisting after a mixed or high-carb meal); >1.0 means net lipogenesis or carryover carb oxidation. The FQ of the high-fat test meal will be used.	Day 8
ΔRespiratory Exchange Ratio Nadir	This represents the drop from a reference RER (typically pre-meal fasting baseline, sometimes overnight minimum) to the lowest RER value observed. In a high-fat meal challenge this captures the magnitude of the fat-oxidation excursion: how far down the RER pushes when the meal is fat-dominant.	Day 8
Post-meal Respiratory Exchange Ratio Slope	This represents the rate of RER change in the early postprandial window, usually fit as a linear slope over the first 30-90 minutes after ingestion. A steep slope would mean a rapid switch (metabolically flexible) and a shallow slope would indicate impaired metabolic flexibility.	Day 8
Time to Respiratory Exchange Ratio Nadir	This represents the amount of minutes from high-fat meal meal ingestion until RER reaches its lowest value. Pairing this will the change in RER nadir helps describe the fat oxidation excursion. That is, nadir magnitude expresses how much fat oxidation increased, whereas time-to-nadir exhibits how long it took to get there.	Day 8

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Skeletal Muscle Mass	Skeletal muscle mass will be measured using D3-creatine dilution. Participants will be administered a 60 mg capsule with D3-creatine during Visit 1. Spot urine specimens will be collected between 120 hours (5 days) and 144 hours (6 days) after administration of the D3-creatine dose.	Day 1 to Day 5
Fat-free Mass	Fat-free mass will be quantified by dual-energy X-ray absorptiometry and two bioelectrical impedance analysis devices (InBody S10 and ImpediMed SFB7) during visit 1.	Day 1
Fat Mass	Fat mass will be estimated by dual-energy X-ray absorptiometry and two bioelectrical impedance analysis devices (InBody S10 and ImpediMed SFB7) during visit 1.	Day 1
Body Fat Percentage	Body fat percentage will be estimated by dual-energy X-ray absorptiometry and two bioelectrical impedance analysis devices (InBody S10 and ImpediMed SFB7) during visit 1.	Day 1
Extracellular Water	At Visit 1, a blood sample of 3 ml will be collected before ingesting an appropriate amount of sodium bromide based on body weight diluted in deionized water. A blood sample of 3 ml will be collected 4 hours after ingestion. During the 4-hour period participants must refrain from eating anything, but they can drink water if needed.	Day 1
Total Body Water	Total body water will be determined via two bioelectrical impedance devices (InBody S10 and ImpediMed SFB7) and deuterium dilution.	Day 1

Collaborators and Investigators

• Sponsor: Pennington Biomedical Research Center
• Investigators: Principal Investigator: Christian Rodriguez, PhD, Pennington Biomedical Research Center

Publications and helpful links

General Publications

• Schoeller DA. Measurement of energy expenditure in free-living humans by using doubly labeled water. J Nutr. 1988 Nov;118(11):1278-89. doi: 10.1093/jn/118.11.1278.
• Racette SB, Schoeller DA, Luke AH, Shay K, Hnilicka J, Kushner RF. Relative dilution spaces of 2H- and 18O-labeled water in humans. Am J Physiol. 1994 Oct;267(4 Pt 1):E585-90. doi: 10.1152/ajpendo.1994.267.4.E585.
• McDougal DH, Sanchez-Delgado G, Flanagan EW, Marlatt KL, Sparks JR, Yang S, Redman LM, Ravussin E. Validation of a novel approach to assess metabolic flexibility to a high-fat meal in a whole-body room calorimeter. Obesity (Silver Spring). 2025 Apr;33(4):743-753. doi: 10.1002/oby.24245. Epub 2025 Mar 6.
• McDougal DH, Marlatt KL, Beyl RA, Redman LM, Ravussin E. A Novel Approach to Assess Metabolic Flexibility Overnight in a Whole-Body Room Calorimeter. Obesity (Silver Spring). 2020 Nov;28(11):2073-2077. doi: 10.1002/oby.22982. Epub 2020 Sep 27.
• Galgani JE, Fernandez-Verdejo R. Pathophysiological role of metabolic flexibility on metabolic health. Obes Rev. 2021 Feb;22(2):e13131. doi: 10.1111/obr.13131. Epub 2020 Aug 19.
• Kachmar M, Albaugh VL, Yang S, Corpodean F, Heymsfield SB, Katzmarzyk PT, Freedman DS, Schauer PR. Disproportionate increase in BMI of >/=60 kg/m2 in the USA. Lancet Diabetes Endocrinol. 2025 Jun;13(6):463-465. doi: 10.1016/S2213-8587(25)00069-5. Epub 2025 Apr 24. No abstract available.

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): August 1, 2026

Study Registration Dates

• First Submitted: May 13, 2026
• First Submitted That Met QC Criteria: May 26, 2026
• First Posted (Actual): May 29, 2026

Study Record Updates

• Last Update Posted (Actual): May 29, 2026
• Last Update Submitted That Met QC Criteria: May 26, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: body composition; metabolism; metabolic flexibility; extreme obesity
• Additional Relevant MeSH Terms: Nutrition Disorders; Overnutrition; Body Weight; Overweight; Obesity; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Signs and Symptoms; Obesity, Morbid
• Other Study ID Numbers: PBRC 2026-011

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No