Experimental Approach to Test Predictions of Body Weight Regulation Models

Obesity Clinical Trial

— DIP  

Official title:

Experimental Approach to Test Predictions of Body Weight Regulation Models

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06309576
• Other study ID #: PBRC 2023-069
• Status: Not yet recruiting
• Phase: N/A
• Start date: July 2024
• Est. completion date: June 2025

Study information

• Verified date: May 2024
• Source: Pennington Biomedical Research Center
• Contact: Rodrigo Fernandez-Verdejo, PhD
• Phone: 2257632594
• Email: Rodrigo.Fernandez[@]pbrc.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The regulation of human body weight and fatness is not fully understood. Although some models of regulation have been proposed (set point, dual-intervention point, others), no studies have been designed to test their predictions. In this pilot and feasibility study, the investigators will implement an experimental approach to test the predictions of models of body weight regulation in humans. Men and women with either underweight or obesity will be exposed to a 2-day fasting followed by a 2-day ad-libitum refeeding. During the entire fasting-refeeding period, energy intake and expenditure will be accurately measured within metabolic chambers. The investigators will therefore determine the compensatory responses to fasting elicited to prevent weight loss. The results will serve to design and power future studies to better understand body weight regulation.

Description:

Background:

Although body weight regulation models have been proposed, experimental approaches for testing their predictions are lacking. The set point (SP) model proposes that a biologically determined fatness is defended by activating compensatory responses to prevent its change. The dual-intervention point (DIP) model proposes that there are two levels of fatness (lower and upper intervention points) within which fatness is weakly regulated. Compensatory responses would only be activated once the lower or upper intervention points are reached. In response to prolonged fasting, the SP model predicts the compensatory responses to be independent of the initial body weight. In contrast, the DIP model predicts higher responses in individuals who are closer to the lower intervention point (underweight) compared to those who are farther away (obesity). None of these models predicts a different response in men vs. women. Our pilot and feasibility study will implement an experimental approach to test these predictions in humans by thoroughly measuring compensatory responses in energy expenditure and energy intake.

Design:

Twelve individuals (3 men with underweight and 3 with obesity; 3 women with underweight and 3 with obesity) will be kept inpatient in metabolic chambers for 5 consecutive days and exposed to a 1-day energy balance, 2-day fasting, and 2-day ad-libitum refeeding. The primary outcome will be the extent of compensatory response, calculated as the cumulative energy balance during the 5-day inpatient period.

Objectives:

1. To determine the extent of compensatory response induced by a 2-day fasting followed by a 2-day ad-libitum refeeding in humans overall and among different subgroups (underweight, obesity, men, women).

2. To explore the timing of the compensatory responses during a 2-day fasting followed by a 2-day ad-libitum refeeding in humans.

3. To explore potential physiological determinants of the inter-individual variability in the compensatory response induced by a 2-day fasting followed by a 2-day ad-libitum refeeding in humans.

Relevance:

Understanding how body weight is regulated in humans can help to prevent or treat obesity. In this pilot and feasibility study, the investigators propose an experimental approach to test the predictions of two body weight regulation models in response to fasting and explore potential sex differences. These preliminary data will be used to design and power future studies for testing models of body weight regulation in humans.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 12
• Est. completion date: June 2025
• Est. primary completion date: February 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 20 Years to 40 Years

Eligibility

Inclusion Criteria:

• Body mass index lower than 18.5 kg/m2 for the underweight group, or 30 kg/m2 or greater for the obesity group

• 20-40 years old

• Nulliparous and regular menstrual cycle (25-35 days) during the last six months (in women)

• Normal thyroid function, blood count, and chemistry 15 panel (normal plasma glucose will be considered at <100 mg/dL; normal serum HDL cholesterol at =50 mg/dL for women and =40 mg/dL for men; and normal serum triglycerides at <150 mg/dL).

• Self-reported weight stability during the last six months (±3 kg)

• Rate the liking of at least one of the flavored liquid meals (Ensure Plus, Abbot Nutrition) between 5 and 8 on a 9-point Likert scale

• Willing to only drink up to two assigned flavors of Ensure Plus for two consecutive days

Exclusion Criteria:

• Eating disorders as indicated by a global score =2.80 in the Eating Disorder Examination Questionnaire, or a previous diagnosis of an eating disorder

• For the underweight group, having food insecurity (with or without hunger) as assessed by the USDA

• Recreational moderate-intensity physical activity =150 min/week, recreational vigorous-intensity physical activity =75 min/week, or a combination of recreational moderate-intensity and vigorous-intensity physical activity (moderate time + [2 × vigorous time]) =150 min/week as assessed by the Global Physical Activity Questionnaire, or being a professional athlete

• Cigarette or vape smoking

• Intake of more than 14 alcoholic drinks per week

• Use of medications that may affect energy intake and/or expenditure, for example, semaglutide, liraglutide, exenatide, other GLP-1 receptor agonists, phentermine-topiramate, naltrexone-bupropion, orlistat, metformin, SGLT2 inhibitors, pramlintide, levocarnitine, amphetamines, and amphetamine-like drugs

• Human immunodeficiency virus, galactosemia, and lactose intolerance.

• Diseases that affect energy homeostasis including endocrine such as hypo/hyperthyroidism, or type 1 or 2 diabetes; cancer; chronic pulmonary diseases; cardiovascular disease; and renal disease

• History of inflammatory bowel disease (ulcerative colitis, Crohn's), malabsorption syndromes (intestinal, pancreatic), and sprue or gluten intolerance

• Having moderate to severe sleep apnea defined as an oxygen desaturation index >10 times/hour assessed by overnight oximetry to be conducted on the night following the screening visit

• Use of oral hormonal contraceptives or less than 6 months using a hormonal intrauterine device (in women)

• Adults who are unable to consent

• Prisoners

• Currently pregnant or breastfeeding (in women)

Related Conditions & MeSH terms

• Body Weight
• Obesity
• Thinness
• Underweight

Intervention

Behavioral:
• Fasting-refeeding cycle
Participants will be maintained in metabolic chambers and exposed to 1 day of energy balance with a standard diet, 2 days of fasting (only water), and 2 days of ad-libitum refeeding using a liquid diet provided in hydration bladders to avoid portion control.

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Pennington Biomedical Research Center	Tulane University

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Compensatory response	Cumulative energy balance during the fasting-refeeding cycle	The cumulative energy balance is calculated one time using the data of 5 inpatient days
Secondary	Timing of the compensatory response	Cumulative energy balance during different time periods of the 5-day fasting-refeeding cycle	The cumulative energy balance calculated for the following time periods along the 5-day fasting-refeeding cycle: day 1 to 2, day 1 to 3, day 1 to 4, during fasting (day 2 to 3), and during refeeding (day 4 to 5)
Secondary	Protein balance	Protein balance (intake minus oxidation) during the fasting-refeeding cycle	Protein balance is calculated one time using the data of 5 inpatient days
Secondary	Carbohydrate balance	Carbohydrate balance (intake minus oxidation) during the fasting-refeeding cycle	Carbohydrate balance is calculated one time using the data of 5 inpatient days
Secondary	Lipid balance	Lipid balance (intake minus oxidation) during the fasting-refeeding cycle	Lipid balance is calculated one time using the data of 5 inpatient days
Secondary	Overall appetite	Calculated from the results of visual analog scales that record hunger, satiety, fullness, and prospective food consumption	Overall appetite is measured 8 times per day (every 2 hours from approximately 8:00 AM) during the 5 inpatient days
Secondary	Food preference	Measured using the Food Preference Questionnaire	Measured once a day, in the fasting state (at approximately 8:00 AM), during the 5 inpatient days
Secondary	Physical activity	Measured with wrist-worn accelerometers	Measured continuously (i.e. for 24 hours) every day during the 5 inpatient days
Secondary	Sleeping metabolic rate	Measured within the metabolic chamber, between 2:00 and 5:00 AM, and extrapolated to 24 hours	Measured every day during the 5 inpatient days
Secondary	Leptin	Circulating concentrations of leptin	Measured once a day, in the fasting state (at approximately 8:00 AM), during the 5 inpatient days
Secondary	Appetite-regulating hormones	Circulating concentrations of ghrelin, peptide YY, glucagon-like peptide-1, cholecystokinin, insulin	Measured once a day, in the fasting state (at approximately 8:00 AM), during the 5 inpatient days
Secondary	Metabolites	Circulating concentrations of glucose, fatty acids, ketone bodies	Measured once a day, in the fasting state (at approximately 8:00 AM), during the 5 inpatient days
Secondary	Gonadotrophic axis	Circulating concentrations of FSH, LH, estradiol, progesterone, testosterone	Measured once a day, in the fasting state (at approximately 8:00 AM), during the 5 inpatient days
Secondary	Thyroid axis	Circulating concentrations of TSH, T3, free T3, reverse T3, T4, free T4	Measured once a day, in the fasting state (at approximately 8:00 AM), during the 5 inpatient days
Secondary	Hypothalamic-pituitary-adrenal axis	Circulating concentrations of ACTH, cortisol, catecholamines	Measured once a day, in the fasting state (at approximately 8:00 AM), during the 5 inpatient days