Evaluating Metabolic Health in Individuals With Extreme Obesity

Official title

Evaluating Energy Metabolism and Metabolic Health in Individuals With Extreme Obesity

Overview

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.

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.

Interventions

• 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).

Primary outcome measures

• 24-hour Energy Expenditure [Time frame: Day 9]
• 24-hour Fat Oxidation [Time frame: Day 9]
• Basal Energy Expenditure [Time frame: Day 9]
• Resting Energy Expenditure [Time frame: Day 9]
• Sleeping Metabolic Rate [Time frame: Day 9]
• Thermic Effect of Food [Time frame: Day 9]
• Spontaneous Physical Activity [Time frame: Day 9]
• Free-living Total Daily Energy Expenditure [Time frame: Day 1 to Day 8]

Secondary outcome measures (5)

• Time to Food Quotient [Time frame: Day 8]
• Respiratory Exchange Ratio: Food Quotient Ratio [Time frame: Day 8]
• ΔRespiratory Exchange Ratio Nadir [Time frame: Day 8]
• Post-meal Respiratory Exchange Ratio Slope [Time frame: Day 8]
• Time to Respiratory Exchange Ratio Nadir [Time frame: Day 8]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Observational model

Cohort

Study locations

Center list to be confirmed — check the primary protocol.

Publications

• 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. PMID 7943308
• 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. PMID 3142975
• 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. PMID 40051190
• 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. PMID 32985108
• 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. PMID 32815226
• 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. PMID 40288378

Identifiers

NCT: NCT07613255 · PBRC 2026-011

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗