Gluco-Food: Study of the Effects of Overfeeding on Glucocorticoids in Lean and Obese Subjects

Sponsor

Eleonora Seelig (Other)

Overall Status

Completed

CT.gov ID

NCT04482738

Collaborator

Novartis (Industry)

Enrollment

Location

9.3

Actual Duration (Months)

3.9

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Investigators suggest that in lean subjects cortisol increases in response to overfeeding and that this increase is blunted in obese subjects. A group of 18 male healthy lean subjects and another group of 18 male healthy obese subjects will undergo a high-calorie meal test. Prior to the meal intake, an indirect calorimetry, bioelectrical impedance, heart rate variability, a fasting blood sample and a perceived stress questionnaire will be assessed. After intake of the study meal, blood tests will be performed in order to measure the secretion of cortisol, glucose and lipid metabolism and inflammatory markers. Indirect calorimetry will be assessed again 60 and 180 minutes after the meal intake.

Condition or Disease	Intervention/Treatment	Phase
Overweight and Obesity	Other: High-calorie meal

Detailed Description

Obesity is one of the most serious health problems in the 21st century. High energy food and a sedentary lifestyle are driving the current obesity pandemic. These factors activate the hypothalamic-pituitary-adrenal (HPA) axis, the key regulatory pathway of energy homeostasis. Activation of the HPA-axis leads to secretion of glucocorticoids from the adrenal glands, which control energy homeostasis by mobilizing and redistributing energy substrates.

Animal models of obesity have shown that glucocorticoids play a key role in the development of the metabolic syndrome. However, studies in humans yielded conflicting results. These studies have a major limitation in common. They do not consider glucocorticoid rhythmicity but rather investigate a snapshot of glucocorticoid secretion. Rhythmicity, however, is crucial because already minor glucocorticoid phase disturbances cause disease and could contribute to obesity.

Interestingly, excessive food intake may increase cortisol levels in healthy subjects . The consequence of this food-induced cortisol peak is not understood, but it may be key to restoring energy homeostasis after a meal. Whether the food-induced cortisol peak in obese subjects is disturbed is not known

With this study, investigators aim to better understand the role played by glucocorticoids in the origin of overweight and obesity. Researchers will investigate, in lean and obese subjects, whether the pulsatile release of cortisol increases after intake of a high-calorie meal. 36 subjects will take part in the study: a group of 18 male lean subjects and a second group of 18 male obese patients.

Study Design

Study Type:

Observational

Actual Enrollment :

36 participants

Observational Model:

Case-Control

Time Perspective:

Cross-Sectional

Official Title:

The Acute Response of Glucocorticoids Upon Food Intake

Actual Study Start Date :

May 14, 2020

Actual Primary Completion Date :

Feb 20, 2021

Actual Study Completion Date :

Feb 20, 2021

Arms and Interventions

Arm	Intervention/Treatment
Lean subjects 24 hours before the study visit, participants will be asked to refrain from alcohol and strenuous exercise. Patients will be asked to remain fasted 10 hours before the study visit takes place. On the day of the study visit, patients will be admitted to the hospital and, after intake of the study meal, blood samples will be taken.	Other: High-calorie meal Intake of a high-calorie meal (2500-3000 calories) within 15 minutes.
Obese subjects 24 hours before the study visit, participants will be asked to refrain from alcohol and strenuous exercise. Patients will be asked to remain fasted 10 hours before the study visit takes place. On the day of the study visit, patients will be admitted to the hospital and, after intake of the study meal, blood samples will be taken.	Other: High-calorie meal Intake of a high-calorie meal (2500-3000 calories) within 15 minutes.

Arm

Intervention/Treatment

Lean subjects

24 hours before the study visit, participants will be asked to refrain from alcohol and strenuous exercise. Patients will be asked to remain fasted 10 hours before the study visit takes place. On the day of the study visit, patients will be admitted to the hospital and, after intake of the study meal, blood samples will be taken.

Other: High-calorie meal

Intake of a high-calorie meal (2500-3000 calories) within 15 minutes.

Obese subjects

Other: High-calorie meal

Intake of a high-calorie meal (2500-3000 calories) within 15 minutes.

Outcome Measures

Primary Outcome Measures

Change in pulsatile secretion of cortisol in response to a high-calorie meal (nmol/l) [195 minutes]
Blood test

Secondary Outcome Measures

Thyroid hormones (nmol/l) [195 minutes]
Blood test
Growth Hormone (mIU/l) [195 minutes]
Blood test
Catecholamines (pg/ml) [195 minutes]
Blood test
Adrenocorticotropic Hormone (ACTH) (pg/ml) [195 minutes]
Blood test
Glucagon-like-peptide-1 (GLP-1) (pg/ml) [195 minutes]
Blood test
Gastric inhibitory polypeptide (GIP) (pg/ml) [195 minutes]
Blood test
Peptide YY (PYY) (pg/ml) [195 minutes]
Blood test
Glucose (mmol/l) [195 minutes]
Blood test
Insulin (mIU/l) [195 minutes]
Blood test
C-Peptide (pmol/l) [195 minutes]
Blood test
Total cholesterol (mmol/l) [195 minutes]
Blood test
Low density lipoprotein (LDL)-cholesterol (mmol/l) [195 minutes]
Blood test
High density lipoprotein (HDL)-cholesterol (mmol/l) [195 minutes]
Blood test
Triglycerides (mmol/l) [195 minutes]
Blood test
Growth differentiation factor 15 (GDF15) (ng/l) [195 minutes]
Blood test
High-sensitive c-reactive Protein (hsCRP) (mg/l) [195 minutes]
Blood test
Interleukin-6 (IL-6) (pg/ml) [195 minutes]
Blood test
Interleukin-8 (IL-8) (pg/ml) [195 minutes]
Blood test
Interleukin-1 receptor Antagonist (IL-1Ra) (pg/ml) [195 minutes]
Blood test
Heart rate (bpm) [5 minutes]
Heart rate variability analysis
Blood pressure: diastolic and systolic blood pressure (mmHg) [1 minute]
Standard blood pressure monitor
Weight: kilogram body weight (kg) [1 minute]
Standard scale
Energy expenditure: basal metabolic rate [200 minutes]
Indirect calorimetry
Substrate utilisation: respiratory quotient [200 minutes]
Indirect calorimetry
Fat and lean mass (kg) [20 minutes]
Body impedance analysis
Total body water (l) [20 minutes]
Body impedance analysis
Appetite: visual analogue scale rating [3 hours]
Visual analogue scale
Stress: perceived stress Levels (0-56) [5 minutes]
Perceived stress questionnaire

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 40 Years

Sexes Eligible for Study:

Male

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Body mass index (BMI) >18,5 and <25 kg/m2
BMI >30 kg/m2

Exclusion Criteria:

Any clinically significant concomitant diseases in lean subjects
Any clinically significant concomitant diseases in obese subjects apart from features of the metabolic syndrome (dyslipidemia, arterial hypertension and insulin resistance)
Lactose intolerance
Severe food allergy
Regular alcohol consumption (>30 g/d)
Regular fitness training (>4 hours/week)
Previous enrolment in a clinical trial within the last 3 months
Inability or contradictions to undergo the investigated intervention
Inability to follow the procedures of the study