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

• ClinicalTrials.gov Identifier: NCT04482738
• Recruitment Status: Completed
• First Posted: July 22, 2020
• Last Update Posted: March 23, 2022
• Sponsor: Eleonora Seelig
• Collaborator: Novartis
• Information provided by (Responsible Party): Eleonora Seelig, University Hospital, Basel, Switzerland

Tracking Information

• First Submitted Date: March 30, 2020
• First Posted Date: July 22, 2020
• Last Update Posted Date: March 23, 2022
• Actual Study Start Date: May 14, 2020
• Actual Primary Completion Date: February 20, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 17, 2020)

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

Blood test

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: July 17, 2020)

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

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study of the Effects of Overfeeding on Glucocorticoids in Lean and Obese Subjects
• Official Title: The Acute Response of Glucocorticoids Upon Food Intake
• 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.

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 Type: Observational
• Study Design: Observational Model: Case-Control; Time Perspective: Cross-Sectional
• Target Follow-Up Duration: Not Provided

Biospecimen

Retention:   Samples Without DNA

Description:

Blood samples

• Sampling Method: Non-Probability Sample
• Study Population: Community sample. The obese group will be both a community and a clinical sample.
• Condition: Overweight and Obesity

Intervention

Other: High-calorie meal

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

Study Groups/Cohorts

• 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.
  Intervention: Other: High-calorie meal
• 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.
  Intervention: Other: High-calorie meal

Publications *

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• Livingstone DE, Jones GC, Smith K, Jamieson PM, Andrew R, Kenyon CJ, Walker BR. Understanding the role of glucocorticoids in obesity: tissue-specific alterations of corticosterone metabolism in obese Zucker rats. Endocrinology. 2000 Feb;141(2):560-3.
• Liu Y, Nakagawa Y, Wang Y, Li R, Li X, Ohzeki T, Friedman TC. Leptin activation of corticosterone production in hepatocytes may contribute to the reversal of obesity and hyperglycemia in leptin-deficient ob/ob mice. Diabetes. 2003 Jun;52(6):1409-16.
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• Mårin P, Darin N, Amemiya T, Andersson B, Jern S, Björntorp P. Cortisol secretion in relation to body fat distribution in obese premenopausal women. Metabolism. 1992 Aug;41(8):882-6.
• Duclos M, Corcuff JB, Etcheverry N, Rashedi M, Tabarin A, Roger P. Abdominal obesity increases overnight cortisol excretion. J Endocrinol Invest. 1999 Jun;22(6):465-71.
• Pasquali R, Cantobelli S, Casimirri F, Capelli M, Bortoluzzi L, Flamia R, Labate AM, Barbara L. The hypothalamic-pituitary-adrenal axis in obese women with different patterns of body fat distribution. J Clin Endocrinol Metab. 1993 Aug;77(2):341-6.
• Chalew SA, Lozano RA, Armour KM, Zadik Z, Kowarski AA. Reduction of plasma cortisol levels in childhood obesity. J Pediatr. 1991 Nov;119(5):778-80.
• Chalew SA, Nagel H, Burt D, Edwards CR. The integrated concentration of cortisone is reduced in obese children. J Pediatr Endocrinol Metab. 1997 May-Jun;10(3):287-90.
• Jessop DS, Dallman MF, Fleming D, Lightman SL. Resistance to glucocorticoid feedback in obesity. J Clin Endocrinol Metab. 2001 Sep;86(9):4109-14.
• Strain GW, Zumoff B, Strain JJ, Levin J, Fukushima DK. Cortisol production in obesity. Metabolism. 1980 Oct;29(10):980-5.
• Pasquali R, Anconetani B, Chattat R, Biscotti M, Spinucci G, Casimirri F, Vicennati V, Carcello A, Labate AM. Hypothalamic-pituitary-adrenal axis activity and its relationship to the autonomic nervous system in women with visceral and subcutaneous obesity: effects of the corticotropin-releasing factor/arginine-vasopressin test and of stress. Metabolism. 1996 Mar;45(3):351-6.
• Rosmond R, Dallman MF, Björntorp P. Stress-related cortisol secretion in men: relationships with abdominal obesity and endocrine, metabolic and hemodynamic abnormalities. J Clin Endocrinol Metab. 1998 Jun;83(6):1853-9.
• Longui CA, Giusti MM, Calliari LE, Katiki T, Kochi C, Monte O. Partial glucocorticoid resistance in obese children detected by very low dose dexamethasone suppression test. J Pediatr Endocrinol Metab. 2003 Dec;16(9):1277-82.
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• Woods C, Tomlinson JW. The Dehydrogenase Hypothesis. Adv Exp Med Biol. 2015;872:353-80. doi: 10.1007/978-1-4939-2895-8_16. Review.
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• Benedict C, Hallschmid M, Scheibner J, Niemeyer D, Schultes B, Merl V, Fehm HL, Born J, Kern W. Gut protein uptake and mechanisms of meal-induced cortisol release. J Clin Endocrinol Metab. 2005 Mar;90(3):1692-6. Epub 2004 Dec 7.
• Follenius M, Brandenberger G, Hietter B. Diurnal cortisol peaks and their relationships to meals. J Clin Endocrinol Metab. 1982 Oct;55(4):757-61.
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• GBD 2015 Obesity Collaborators, Afshin A, Forouzanfar MH, Reitsma MB, Sur P, Estep K, Lee A, Marczak L, Mokdad AH, Moradi-Lakeh M, Naghavi M, Salama JS, Vos T, Abate KH, Abbafati C, Ahmed MB, Al-Aly Z, Alkerwi A, Al-Raddadi R, Amare AT, Amberbir A, Amegah AK, Amini E, Amrock SM, Anjana RM, Ärnlöv J, Asayesh H, Banerjee A, Barac A, Baye E, Bennett DA, Beyene AS, Biadgilign S, Biryukov S, Bjertness E, Boneya DJ, Campos-Nonato I, Carrero JJ, Cecilio P, Cercy K, Ciobanu LG, Cornaby L, Damtew SA, Dandona L, Dandona R, Dharmaratne SD, Duncan BB, Eshrati B, Esteghamati A, Feigin VL, Fernandes JC, Fürst T, Gebrehiwot TT, Gold A, Gona PN, Goto A, Habtewold TD, Hadush KT, Hafezi-Nejad N, Hay SI, Horino M, Islami F, Kamal R, Kasaeian A, Katikireddi SV, Kengne AP, Kesavachandran CN, Khader YS, Khang YH, Khubchandani J, Kim D, Kim YJ, Kinfu Y, Kosen S, Ku T, Defo BK, Kumar GA, Larson HJ, Leinsalu M, Liang X, Lim SS, Liu P, Lopez AD, Lozano R, Majeed A, Malekzadeh R, Malta DC, Mazidi M, McAlinden C, McGarvey ST, Mengistu DT, Mensah GA, Mensink GBM, Mezgebe HB, Mirrakhimov EM, Mueller UO, Noubiap JJ, Obermeyer CM, Ogbo FA, Owolabi MO, Patton GC, Pourmalek F, Qorbani M, Rafay A, Rai RK, Ranabhat CL, Reinig N, Safiri S, Salomon JA, Sanabria JR, Santos IS, Sartorius B, Sawhney M, Schmidhuber J, Schutte AE, Schmidt MI, Sepanlou SG, Shamsizadeh M, Sheikhbahaei S, Shin MJ, Shiri R, Shiue I, Roba HS, Silva DAS, Silverberg JI, Singh JA, Stranges S, Swaminathan S, Tabarés-Seisdedos R, Tadese F, Tedla BA, Tegegne BS, Terkawi AS, Thakur JS, Tonelli M, Topor-Madry R, Tyrovolas S, Ukwaja KN, Uthman OA, Vaezghasemi M, Vasankari T, Vlassov VV, Vollset SE, Weiderpass E, Werdecker A, Wesana J, Westerman R, Yano Y, Yonemoto N, Yonga G, Zaidi Z, Zenebe ZM, Zipkin B, Murray CJL. Health Effects of Overweight and Obesity in 195 Countries over 25 Years. N Engl J Med. 2017 Jul 6;377(1):13-27. doi: 10.1056/NEJMoa1614362. Epub 2017 Jun 12.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: July 17, 2020): 36
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: February 20, 2021
• Actual Primary Completion Date: February 20, 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: Male

• Ages: 18 Years to 40 Years (Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Switzerland

Administrative Information

• NCT Number: NCT04482738
• Other Study ID Numbers: 202000384
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Eleonora Seelig, University Hospital, Basel, Switzerland
• Original Responsible Party: Same as current
• Current Study Sponsor: Eleonora Seelig
• Original Study Sponsor: Same as current
• Collaborators: Novartis

Investigators

• Principal Investigator: Eleonora Seelig, MD; University Hospital, Basel, Switzerland

• PRS Account: University Hospital, Basel, Switzerland
• Verification Date: March 2022