<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT04482738</url>
  </required_header>
  <id_info>
    <org_study_id>202000384</org_study_id>
    <nct_id>NCT04482738</nct_id>
  </id_info>
  <brief_title>Study of the Effects of Overfeeding on Glucocorticoids in Lean and Obese Subjects</brief_title>
  <acronym>Gluco-Food</acronym>
  <official_title>The Acute Response of Glucocorticoids Upon Food Intake</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Eleonora Seelig</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Novartis</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>University Hospital, Basel, Switzerland</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Investigators suggest that in lean subjects cortisol increases in response to overfeeding and&#xD;
      that this increase is blunted in obese subjects. A group of 18 male healthy lean subjects and&#xD;
      another group of 18 male healthy obese subjects will undergo a high-calorie meal test. Prior&#xD;
      to the meal intake, an indirect calorimetry, bioelectrical impedance, heart rate variability,&#xD;
      a fasting blood sample and a perceived stress questionnaire will be assessed. After intake of&#xD;
      the study meal, blood tests will be performed in order to measure the secretion of cortisol,&#xD;
      glucose and lipid metabolism and inflammatory markers. Indirect calorimetry will be assessed&#xD;
      again 60 and 180 minutes after the meal intake.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Obesity is one of the most serious health problems in the 21st century. High energy food and&#xD;
      a sedentary lifestyle are driving the current obesity pandemic. These factors activate the&#xD;
      hypothalamic-pituitary-adrenal (HPA) axis, the key regulatory pathway of energy homeostasis.&#xD;
      Activation of the HPA-axis leads to secretion of glucocorticoids from the adrenal glands,&#xD;
      which control energy homeostasis by mobilizing and redistributing energy substrates.&#xD;
&#xD;
      Animal models of obesity have shown that glucocorticoids play a key role in the development&#xD;
      of the metabolic syndrome. However, studies in humans yielded conflicting results. These&#xD;
      studies have a major limitation in common. They do not consider glucocorticoid rhythmicity&#xD;
      but rather investigate a snapshot of glucocorticoid secretion. Rhythmicity, however, is&#xD;
      crucial because already minor glucocorticoid phase disturbances cause disease and could&#xD;
      contribute to obesity.&#xD;
&#xD;
      Interestingly, excessive food intake may increase cortisol levels in healthy subjects . The&#xD;
      consequence of this food-induced cortisol peak is not understood, but it may be key to&#xD;
      restoring energy homeostasis after a meal. Whether the food-induced cortisol peak in obese&#xD;
      subjects is disturbed is not known&#xD;
&#xD;
      With this study, investigators aim to better understand the role played by glucocorticoids in&#xD;
      the origin of overweight and obesity. Researchers will investigate, in lean and obese&#xD;
      subjects, whether the pulsatile release of cortisol increases after intake of a high-calorie&#xD;
      meal. 36 subjects will take part in the study: a group of 18 male lean subjects and a second&#xD;
      group of 18 male obese patients.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">May 14, 2020</start_date>
  <completion_date type="Actual">February 20, 2021</completion_date>
  <primary_completion_date type="Actual">February 20, 2021</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Control</observational_model>
    <time_perspective>Cross-Sectional</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Change in pulsatile secretion of cortisol in response to a high-calorie meal (nmol/l)</measure>
    <time_frame>195 minutes</time_frame>
    <description>Blood test</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Thyroid hormones (nmol/l)</measure>
    <time_frame>195 minutes</time_frame>
    <description>Blood test</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Growth Hormone (mIU/l)</measure>
    <time_frame>195 minutes</time_frame>
    <description>Blood test</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Catecholamines (pg/ml)</measure>
    <time_frame>195 minutes</time_frame>
    <description>Blood test</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adrenocorticotropic Hormone (ACTH) (pg/ml)</measure>
    <time_frame>195 minutes</time_frame>
    <description>Blood test</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Glucagon-like-peptide-1 (GLP-1) (pg/ml)</measure>
    <time_frame>195 minutes</time_frame>
    <description>Blood test</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Gastric inhibitory polypeptide (GIP) (pg/ml)</measure>
    <time_frame>195 minutes</time_frame>
    <description>Blood test</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Peptide YY (PYY) (pg/ml)</measure>
    <time_frame>195 minutes</time_frame>
    <description>Blood test</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Glucose (mmol/l)</measure>
    <time_frame>195 minutes</time_frame>
    <description>Blood test</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Insulin (mIU/l)</measure>
    <time_frame>195 minutes</time_frame>
    <description>Blood test</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>C-Peptide (pmol/l)</measure>
    <time_frame>195 minutes</time_frame>
    <description>Blood test</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Total cholesterol (mmol/l)</measure>
    <time_frame>195 minutes</time_frame>
    <description>Blood test</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Low density lipoprotein (LDL)-cholesterol (mmol/l)</measure>
    <time_frame>195 minutes</time_frame>
    <description>Blood test</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>High density lipoprotein (HDL)-cholesterol (mmol/l)</measure>
    <time_frame>195 minutes</time_frame>
    <description>Blood test</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Triglycerides (mmol/l)</measure>
    <time_frame>195 minutes</time_frame>
    <description>Blood test</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Growth differentiation factor 15 (GDF15) (ng/l)</measure>
    <time_frame>195 minutes</time_frame>
    <description>Blood test</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>High-sensitive c-reactive Protein (hsCRP) (mg/l)</measure>
    <time_frame>195 minutes</time_frame>
    <description>Blood test</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Interleukin-6 (IL-6) (pg/ml)</measure>
    <time_frame>195 minutes</time_frame>
    <description>Blood test</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Interleukin-8 (IL-8) (pg/ml)</measure>
    <time_frame>195 minutes</time_frame>
    <description>Blood test</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Interleukin-1 receptor Antagonist (IL-1Ra) (pg/ml)</measure>
    <time_frame>195 minutes</time_frame>
    <description>Blood test</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Heart rate (bpm)</measure>
    <time_frame>5 minutes</time_frame>
    <description>Heart rate variability analysis</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Blood pressure: diastolic and systolic blood pressure (mmHg)</measure>
    <time_frame>1 minute</time_frame>
    <description>Standard blood pressure monitor</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Weight: kilogram body weight (kg)</measure>
    <time_frame>1 minute</time_frame>
    <description>Standard scale</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Energy expenditure: basal metabolic rate</measure>
    <time_frame>200 minutes</time_frame>
    <description>Indirect calorimetry</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Substrate utilisation: respiratory quotient</measure>
    <time_frame>200 minutes</time_frame>
    <description>Indirect calorimetry</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Fat and lean mass (kg)</measure>
    <time_frame>20 minutes</time_frame>
    <description>Body impedance analysis</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Total body water (l)</measure>
    <time_frame>20 minutes</time_frame>
    <description>Body impedance analysis</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Appetite: visual analogue scale rating</measure>
    <time_frame>3 hours</time_frame>
    <description>Visual analogue scale</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Stress: perceived stress Levels (0-56)</measure>
    <time_frame>5 minutes</time_frame>
    <description>Perceived stress questionnaire</description>
  </secondary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Actual">36</enrollment>
  <condition>Overweight and Obesity</condition>
  <arm_group>
    <arm_group_label>Lean subjects</arm_group_label>
    <description>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.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Obese subjects</arm_group_label>
    <description>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.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>High-calorie meal</intervention_name>
    <description>Intake of a high-calorie meal (2500-3000 calories) within 15 minutes.</description>
    <arm_group_label>Lean subjects</arm_group_label>
    <arm_group_label>Obese subjects</arm_group_label>
  </intervention>
  <biospec_retention>Samples Without DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Blood samples&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Community sample. The obese group will be both a community and a clinical sample.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Body mass index (BMI) &gt;18,5 and &lt;25 kg/m2&#xD;
&#xD;
          -  BMI &gt;30 kg/m2&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Any clinically significant concomitant diseases in lean subjects&#xD;
&#xD;
          -  Any clinically significant concomitant diseases in obese subjects apart from features&#xD;
             of the metabolic syndrome (dyslipidemia, arterial hypertension and insulin resistance)&#xD;
&#xD;
          -  Lactose intolerance&#xD;
&#xD;
          -  Severe food allergy&#xD;
&#xD;
          -  Regular alcohol consumption (&gt;30 g/d)&#xD;
&#xD;
          -  Regular fitness training (&gt;4 hours/week)&#xD;
&#xD;
          -  Previous enrolment in a clinical trial within the last 3 months&#xD;
&#xD;
          -  Inability or contradictions to undergo the investigated intervention&#xD;
&#xD;
          -  Inability to follow the procedures of the study&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>40 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Eleonora Seelig, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University Hospital, Basel, Switzerland</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University Hospital Basel</name>
      <address>
        <city>Basel</city>
        <state>Basel-Stadt</state>
        <zip>4031</zip>
        <country>Switzerland</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Switzerland</country>
  </location_countries>
  <reference>
    <citation>Prospective Studies Collaboration; Whitlock G, Lewington S, Sherliker P, Clarke R, Emberson J, Halsey J, Qizilbash N, Collins R, Peto R. Body-mass index and cause-specific mortality in 900 000 adults: collaborative analyses of 57 prospective studies. Lancet. 2009 Mar 28;373(9669):1083-96. doi: 10.1016/S0140-6736(09)60318-4. Epub 2009 Mar 18.</citation>
    <PMID>19299006</PMID>
  </reference>
  <reference>
    <citation>van der Klaauw AA, Farooqi IS. The hunger genes: pathways to obesity. Cell. 2015 Mar 26;161(1):119-132. doi: 10.1016/j.cell.2015.03.008.</citation>
    <PMID>25815990</PMID>
  </reference>
  <reference>
    <citation>Vgontzas AN, Lin HM, Papaliaga M, Calhoun S, Vela-Bueno A, Chrousos GP, Bixler EO. Short sleep duration and obesity: the role of emotional stress and sleep disturbances. Int J Obes (Lond). 2008 May;32(5):801-9. doi: 10.1038/ijo.2008.4. Epub 2008 Feb 5.</citation>
    <PMID>18253159</PMID>
  </reference>
  <reference>
    <citation>de Guia RM, Rose AJ, Herzig S. Glucocorticoid hormones and energy homeostasis. Horm Mol Biol Clin Investig. 2014 Aug;19(2):117-28. doi: 10.1515/hmbci-2014-0021.</citation>
    <PMID>25390020</PMID>
  </reference>
  <reference>
    <citation>Russell G, Lightman S. The human stress response. Nat Rev Endocrinol. 2019 Sep;15(9):525-534. doi: 10.1038/s41574-019-0228-0. Epub 2019 Jun 27.</citation>
    <PMID>31249398</PMID>
  </reference>
  <reference>
    <citation>Ferrau F, Korbonits M. Metabolic Syndrome in Cushing's Syndrome Patients. Front Horm Res. 2018;49:85-103. doi: 10.1159/000486002. Epub 2018 Apr 5.</citation>
    <PMID>29894989</PMID>
  </reference>
  <reference>
    <citation>Livingstone DE, Grassick SL, Currie GL, Walker BR, Andrew R. Dysregulation of glucocorticoid metabolism in murine obesity: comparable effects of leptin resistance and deficiency. J Endocrinol. 2009 May;201(2):211-8. doi: 10.1677/JOE-09-0003. Epub 2009 Feb 17.</citation>
    <PMID>19223399</PMID>
  </reference>
  <reference>
    <citation>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. doi: 10.1210/endo.141.2.7297.</citation>
    <PMID>10650936</PMID>
  </reference>
  <reference>
    <citation>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. doi: 10.2337/diabetes.52.6.1409.</citation>
    <PMID>12765951</PMID>
  </reference>
  <reference>
    <citation>Chalew S, Nagel H, Shore S. The hypothalamic-pituitary-adrenal axis in obesity. Obes Res. 1995 Jul;3(4):371-82. doi: 10.1002/j.1550-8528.1995.tb00163.x.</citation>
    <PMID>8521154</PMID>
  </reference>
  <reference>
    <citation>Marin P, Darin N, Amemiya T, Andersson B, Jern S, Bjorntorp P. Cortisol secretion in relation to body fat distribution in obese premenopausal women. Metabolism. 1992 Aug;41(8):882-6. doi: 10.1016/0026-0495(92)90171-6.</citation>
    <PMID>1640867</PMID>
  </reference>
  <reference>
    <citation>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. doi: 10.1007/BF03343591.</citation>
    <PMID>10435857</PMID>
  </reference>
  <reference>
    <citation>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. doi: 10.1210/jcem.77.2.8393881.</citation>
    <PMID>8393881</PMID>
  </reference>
  <reference>
    <citation>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. doi: 10.1016/s0022-3476(05)80302-6. No abstract available.</citation>
    <PMID>1941386</PMID>
  </reference>
  <reference>
    <citation>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. doi: 10.1515/JPEM.1997.10.3.287.</citation>
    <PMID>9388820</PMID>
  </reference>
  <reference>
    <citation>Jessop DS, Dallman MF, Fleming D, Lightman SL. Resistance to glucocorticoid feedback in obesity. J Clin Endocrinol Metab. 2001 Sep;86(9):4109-14. doi: 10.1210/jcem.86.9.7826.</citation>
    <PMID>11549634</PMID>
  </reference>
  <reference>
    <citation>Strain GW, Zumoff B, Strain JJ, Levin J, Fukushima DK. Cortisol production in obesity. Metabolism. 1980 Oct;29(10):980-5. doi: 10.1016/0026-0495(80)90043-8.</citation>
    <PMID>6999293</PMID>
  </reference>
  <reference>
    <citation>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. doi: 10.1016/s0026-0495(96)90290-5.</citation>
    <PMID>8606643</PMID>
  </reference>
  <reference>
    <citation>Rosmond R, Dallman MF, Bjorntorp 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. doi: 10.1210/jcem.83.6.4843.</citation>
    <PMID>9626108</PMID>
  </reference>
  <reference>
    <citation>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. doi: 10.1515/jpem.2003.16.9.1277.</citation>
    <PMID>14714751</PMID>
  </reference>
  <reference>
    <citation>Ljung T, Andersson B, Bengtsson BA, Bjorntorp P, Marin P. Inhibition of cortisol secretion by dexamethasone in relation to body fat distribution: a dose-response study. Obes Res. 1996 May;4(3):277-82. doi: 10.1002/j.1550-8528.1996.tb00546.x.</citation>
    <PMID>8732962</PMID>
  </reference>
  <reference>
    <citation>Woods C, Tomlinson JW. The Dehydrogenase Hypothesis. Adv Exp Med Biol. 2015;872:353-80. doi: 10.1007/978-1-4939-2895-8_16.</citation>
    <PMID>26216003</PMID>
  </reference>
  <reference>
    <citation>van Rossum EF. Obesity and cortisol: New perspectives on an old theme. Obesity (Silver Spring). 2017 Mar;25(3):500-501. doi: 10.1002/oby.21774. No abstract available.</citation>
    <PMID>28229549</PMID>
  </reference>
  <reference>
    <citation>Al-Damluji S, Iveson T, Thomas JM, Pendlebury DJ, Rees LH, Besser GM. Food-induced cortisol secretion is mediated by central alpha-1 adrenoceptor modulation of pituitary ACTH secretion. Clin Endocrinol (Oxf). 1987 May;26(5):629-36. doi: 10.1111/j.1365-2265.1987.tb00819.x.</citation>
    <PMID>2822298</PMID>
  </reference>
  <reference>
    <citation>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. doi: 10.1210/jc.2004-1792. Epub 2004 Dec 7.</citation>
    <PMID>15585568</PMID>
  </reference>
  <reference>
    <citation>Follenius M, Brandenberger G, Hietter B. Diurnal cortisol peaks and their relationships to meals. J Clin Endocrinol Metab. 1982 Oct;55(4):757-61. doi: 10.1210/jcem-55-4-757.</citation>
    <PMID>7202017</PMID>
  </reference>
  <reference>
    <citation>Ibrahim M, Bonfiglio S, Schlogl M, Vinales KL, Piaggi P, Venti C, Walter M, Krakoff J, Thearle MS. Energy Expenditure and Hormone Responses in Humans After Overeating High-Fructose Corn Syrup Versus Whole-Wheat Foods. Obesity (Silver Spring). 2018 Jan;26(1):141-149. doi: 10.1002/oby.22068. Epub 2017 Nov 28.</citation>
    <PMID>29193741</PMID>
  </reference>
  <reference>
    <citation>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, Arnlov 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, Furst 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, Tabares-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.</citation>
    <PMID>28604169</PMID>
  </reference>
  <verification_date>March 2022</verification_date>
  <study_first_submitted>March 30, 2020</study_first_submitted>
  <study_first_submitted_qc>July 17, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 22, 2020</study_first_posted>
  <last_update_submitted>March 22, 2022</last_update_submitted>
  <last_update_submitted_qc>March 22, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">March 23, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>University Hospital, Basel, Switzerland</investigator_affiliation>
    <investigator_full_name>Eleonora Seelig</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>obesity</keyword>
  <keyword>overweight</keyword>
  <keyword>cortisol</keyword>
  <keyword>overfeeding</keyword>
  <keyword>glucocorticoids</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Overweight</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04482738
org study id: 202000384
nct id: NCT04482738
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
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.
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.
observational model: Case-Control
time perspective: Cross-Sectional
measure: Change in pulsatile secretion of cortisol in response to a high-calorie meal (nmol/l)
time frame: 195 minutes
description: Blood test
measure: Thyroid hormones (nmol/l)
time frame: 195 minutes
description: Blood test
measure: Growth Hormone (mIU/l)
time frame: 195 minutes
description: Blood test
measure: Catecholamines (pg/ml)
time frame: 195 minutes
description: Blood test
measure: Adrenocorticotropic Hormone (ACTH) (pg/ml)
time frame: 195 minutes
description: Blood test
measure: Glucagon-like-peptide-1 (GLP-1) (pg/ml)
time frame: 195 minutes
description: Blood test
measure: Gastric inhibitory polypeptide (GIP) (pg/ml)
time frame: 195 minutes
description: Blood test
measure: Peptide YY (PYY) (pg/ml)
time frame: 195 minutes
description: Blood test
measure: Glucose (mmol/l)
time frame: 195 minutes
description: Blood test
measure: Insulin (mIU/l)
time frame: 195 minutes
description: Blood test
measure: C-Peptide (pmol/l)
time frame: 195 minutes
description: Blood test
measure: Total cholesterol (mmol/l)
time frame: 195 minutes
description: Blood test
measure: Low density lipoprotein (LDL)-cholesterol (mmol/l)
time frame: 195 minutes
description: Blood test
measure: High density lipoprotein (HDL)-cholesterol (mmol/l)
time frame: 195 minutes
description: Blood test
measure: Triglycerides (mmol/l)
time frame: 195 minutes
description: Blood test
measure: Growth differentiation factor 15 (GDF15) (ng/l)
time frame: 195 minutes
description: Blood test
measure: High-sensitive c-reactive Protein (hsCRP) (mg/l)
time frame: 195 minutes
description: Blood test
measure: Interleukin-6 (IL-6) (pg/ml)
time frame: 195 minutes
description: Blood test
measure: Interleukin-8 (IL-8) (pg/ml)
time frame: 195 minutes
description: Blood test
measure: Interleukin-1 receptor Antagonist (IL-1Ra) (pg/ml)
time frame: 195 minutes
description: Blood test
measure: Heart rate (bpm)
time frame: 5 minutes
description: Heart rate variability analysis
measure: Blood pressure: diastolic and systolic blood pressure (mmHg)
time frame: 1 minute
description: Standard blood pressure monitor
measure: Weight: kilogram body weight (kg)
time frame: 1 minute
description: Standard scale
measure: Energy expenditure: basal metabolic rate
time frame: 200 minutes
description: Indirect calorimetry
measure: Substrate utilisation: respiratory quotient
time frame: 200 minutes
description: Indirect calorimetry
measure: Fat and lean mass (kg)
time frame: 20 minutes
description: Body impedance analysis
measure: Total body water (l)
time frame: 20 minutes
description: Body impedance analysis
measure: Appetite: visual analogue scale rating
time frame: 3 hours
description: Visual analogue scale
measure: Stress: perceived stress Levels (0-56)
time frame: 5 minutes
description: Perceived stress questionnaire
arm group label: Lean subjects
description: 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.
arm group label: Obese subjects
description: 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 type: Other
intervention name: High-calorie meal
description: Intake of a high-calorie meal (2500-3000 calories) within 15 minutes.
arm group label: Lean subjects
arm group label: Obese subjects
Blood samples
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: Male
minimum age: 18 Years
maximum age: 40 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Eleonora Seelig, MD
role: Principal Investigator
affiliation: University Hospital, Basel, Switzerland
facility: 
country: Switzerland
citation: Prospective Studies Collaboration; Whitlock G, Lewington S, Sherliker P, Clarke R, Emberson J, Halsey J, Qizilbash N, Collins R, Peto R. Body-mass index and cause-specific mortality in 900 000 adults: collaborative analyses of 57 prospective studies. Lancet. 2009 Mar 28;373(9669):1083-96. doi: 10.1016/S0140-6736(09)60318-4. Epub 2009 Mar 18.
PMID: 19299006
citation: van der Klaauw AA, Farooqi IS. The hunger genes: pathways to obesity. Cell. 2015 Mar 26;161(1):119-132. doi: 10.1016/j.cell.2015.03.008.
PMID: 25815990
citation: Vgontzas AN, Lin HM, Papaliaga M, Calhoun S, Vela-Bueno A, Chrousos GP, Bixler EO. Short sleep duration and obesity: the role of emotional stress and sleep disturbances. Int J Obes (Lond). 2008 May;32(5):801-9. doi: 10.1038/ijo.2008.4. Epub 2008 Feb 5.
PMID: 18253159
citation: de Guia RM, Rose AJ, Herzig S. Glucocorticoid hormones and energy homeostasis. Horm Mol Biol Clin Investig. 2014 Aug;19(2):117-28. doi: 10.1515/hmbci-2014-0021.
PMID: 25390020
citation: Russell G, Lightman S. The human stress response. Nat Rev Endocrinol. 2019 Sep;15(9):525-534. doi: 10.1038/s41574-019-0228-0. Epub 2019 Jun 27.
PMID: 31249398
citation: Ferrau F, Korbonits M. Metabolic Syndrome in Cushing's Syndrome Patients. Front Horm Res. 2018;49:85-103. doi: 10.1159/000486002. Epub 2018 Apr 5.
PMID: 29894989
citation: Livingstone DE, Grassick SL, Currie GL, Walker BR, Andrew R. Dysregulation of glucocorticoid metabolism in murine obesity: comparable effects of leptin resistance and deficiency. J Endocrinol. 2009 May;201(2):211-8. doi: 10.1677/JOE-09-0003. Epub 2009 Feb 17.
PMID: 19223399
citation: 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. doi: 10.1210/endo.141.2.7297.
PMID: 10650936
citation: 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. doi: 10.2337/diabetes.52.6.1409.
PMID: 12765951
citation: Chalew S, Nagel H, Shore S. The hypothalamic-pituitary-adrenal axis in obesity. Obes Res. 1995 Jul;3(4):371-82. doi: 10.1002/j.1550-8528.1995.tb00163.x.
PMID: 8521154
citation: Marin P, Darin N, Amemiya T, Andersson B, Jern S, Bjorntorp P. Cortisol secretion in relation to body fat distribution in obese premenopausal women. Metabolism. 1992 Aug;41(8):882-6. doi: 10.1016/0026-0495(92)90171-6.
PMID: 1640867
citation: 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. doi: 10.1007/BF03343591.
PMID: 10435857
citation: 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. doi: 10.1210/jcem.77.2.8393881.
PMID: 8393881
citation: 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. doi: 10.1016/s0022-3476(05)80302-6. No abstract available.
PMID: 1941386
citation: 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. doi: 10.1515/JPEM.1997.10.3.287.
PMID: 9388820
citation: Jessop DS, Dallman MF, Fleming D, Lightman SL. Resistance to glucocorticoid feedback in obesity. J Clin Endocrinol Metab. 2001 Sep;86(9):4109-14. doi: 10.1210/jcem.86.9.7826.
PMID: 11549634
citation: Strain GW, Zumoff B, Strain JJ, Levin J, Fukushima DK. Cortisol production in obesity. Metabolism. 1980 Oct;29(10):980-5. doi: 10.1016/0026-0495(80)90043-8.
PMID: 6999293
citation: 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. doi: 10.1016/s0026-0495(96)90290-5.
PMID: 8606643
citation: Rosmond R, Dallman MF, Bjorntorp 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. doi: 10.1210/jcem.83.6.4843.
PMID: 9626108
citation: 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. doi: 10.1515/jpem.2003.16.9.1277.
PMID: 14714751
citation: Ljung T, Andersson B, Bengtsson BA, Bjorntorp P, Marin P. Inhibition of cortisol secretion by dexamethasone in relation to body fat distribution: a dose-response study. Obes Res. 1996 May;4(3):277-82. doi: 10.1002/j.1550-8528.1996.tb00546.x.
PMID: 8732962
citation: Woods C, Tomlinson JW. The Dehydrogenase Hypothesis. Adv Exp Med Biol. 2015;872:353-80. doi: 10.1007/978-1-4939-2895-8_16.
PMID: 26216003
citation: van Rossum EF. Obesity and cortisol: New perspectives on an old theme. Obesity (Silver Spring). 2017 Mar;25(3):500-501. doi: 10.1002/oby.21774. No abstract available.
PMID: 28229549
citation: Al-Damluji S, Iveson T, Thomas JM, Pendlebury DJ, Rees LH, Besser GM. Food-induced cortisol secretion is mediated by central alpha-1 adrenoceptor modulation of pituitary ACTH secretion. Clin Endocrinol (Oxf). 1987 May;26(5):629-36. doi: 10.1111/j.1365-2265.1987.tb00819.x.
PMID: 2822298
citation: 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. doi: 10.1210/jc.2004-1792. Epub 2004 Dec 7.
PMID: 15585568
citation: Follenius M, Brandenberger G, Hietter B. Diurnal cortisol peaks and their relationships to meals. J Clin Endocrinol Metab. 1982 Oct;55(4):757-61. doi: 10.1210/jcem-55-4-757.
PMID: 7202017
citation: Ibrahim M, Bonfiglio S, Schlogl M, Vinales KL, Piaggi P, Venti C, Walter M, Krakoff J, Thearle MS. Energy Expenditure and Hormone Responses in Humans After Overeating High-Fructose Corn Syrup Versus Whole-Wheat Foods. Obesity (Silver Spring). 2018 Jan;26(1):141-149. doi: 10.1002/oby.22068. Epub 2017 Nov 28.
PMID: 29193741
citation: 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, Arnlov 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, Furst 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, Tabares-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.
PMID: 28604169
responsible party type: Sponsor-Investigator
investigator affiliation: University Hospital, Basel, Switzerland
investigator full name: Eleonora Seelig
investigator title: Principal Investigator
mesh term: Overweight
sharing ipd: No