Investigating the Central and Peripheral Mechanisms by Which Glucocorticoids Affect Hunger

The purpose of this study is to examine if glucocorticoids will change neural activation in regions of the corticolimbic-striatal system that regulate feeding.

Study Overview

• Status: Completed
• Conditions: Obesity
• Intervention / Treatment: Drug: hydrocortisone; Other: saline

Detailed Description

The primary hypothesis tested in this study will be to determine if that in response to food cues, glucocorticoids will change neural activation in regions of the corticolimbic-striatal system that regulate feeding. It is anticipate that these changes will correlate with hunger ratings and food intake. Further, this research will also examine if glucocorticoids will increase the basal metabolic rate and alter multiple systemic appetite-regulating hormones compared to saline. It is expected that these changes will correlate positively with hunger ratings and food intake as well.

• Study Type: Interventional
• Enrollment (Actual): 28
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06511
      • Yale University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• BMI < = 26 kg/m2
• Ability to read and write English

Exclusion Criteria:

• Creatinine > 1.5
• Hgb < 10 mg/dL
• ALT > 2.5 x ULN
• Untreated thyroid disease
• Uncontrolled or severe hypertension
• Known neurological disorders
• Diabetes or impaired glucose tolerance
• Untreated or severe psychiatric disorders
• Malignancy
• Endogenous hypercortisolism
• Addison's disease
• Bleeding disorders
• Smoking
• Current or recent steroid use in the last 3 months
• Illicit drug use
• Eating disorders
• Drug or alcohol addiction
• History of claustrophobia
• Pregnancy
• Breastfeeding
• Contraindications to MRI
• Use of any psychoactive medication within the past 3 months

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intravenous glucocorticoids; Subjects in the glucocorticoids arm will receive an infusion of hydrocortisone overnight in the research unit prior to fMRI testing on either the first or second visit.	Drug: hydrocortisone; Hydrocortisone will be used as the steroid of choice because it is bio-identical to cortisol and is subject to the same metabolism as cortisol.
Placebo Comparator: Intravenous saline; Subjects in the saline arm will receive an infusion of saline overnight in the research unit prior to fMRI testing on either the first or second visit.	Other: saline; Saline will be used as the placebo comparator. It will be administered in the same manner as the active drug.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Brain Response to Food Imagery	Brain response to images of food either during hydrocortisone infusion or saline infusion will be measured through fMRI. Brain response is operationally defined as the change in functional MRI-measured blood oxygen levels in specific regions of the brain between the resting state and intervention state. The fMRI sequences last anywhere from 1-5 min. Total scan time will be approximately 90 minutes. The slices taken with each sequences equal 25-75. The outcome is a comparison between the resting oxygen levels and oxygen levels during the interventions. BioImage Suite software is used to categorize if there is a significance between the two levels at a p < 0.05.	90 minutes
Average Hunger Rating	Average hunger rating will be captured using the Visual Food Cue Task. This standardized method presents a series of images consisting of high calorie food, low calorie food, and non-food pictures presented randomly across four runs during the fMRI session. Each picture will be presented only once in a randomized order for each participant. Participants will be instructed to rate their "hunger", "liking" and "wanting" of the item on a 9-point Likert scale utilizing a 4-key button box. The hunger, wanting, and liking scales are all rated on a scale of 1-9, 1 being the least and 9 being the most. These scores are presented as an average across measurement points during the fMRI. Every time a food image is shown, the rater provides a rating of hunger, wanting and liking of it- people will be shown approximately 40-60 photos.	90 minutes

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Average Wanting Rating	Average wanting rating will be captured using the Visual Food Cue Task. This standardized method presents a series of images consisting of high calorie food, low calorie food, and non-food pictures presented randomly across four runs during the fMRI session. Each picture will be presented only once in a randomized order for each participant. Participants will be instructed to rate their "hunger", "liking" and "wanting" of the item on a 9-point Likert scale utilizing a 4-key button box. The hunger, wanting, and liking scales are all rated on a scale of 1-9, 1 being the least and 9 being the most. These scores are presented as an average across measurement points during the fMRI.	90 minutes
Average Liking Rating	Average wanting rating will be captured using the Visual Food Cue Task. This standardized method presents a series of images consisting of high calorie food, low calorie food, and non-food pictures presented randomly across four runs during the fMRI session. Each picture will be presented only once in a randomized order for each participant. Participants will be instructed to rate their "hunger", "liking" and "wanting" of the item on a 9-point Likert scale utilizing a 4-key button box. The hunger, wanting, and liking scales are all rated on a scale of 1-9, 1 being the least and 9 being the most. These scores are presented as an average across measurement points during the fMRI.	90 minutes
Total Cortisol	Total cortisol will be collected from serum at the beginning and end of the procedure.	Baseline
Total Cortisol	Total cortisol will be collected from serum at the beginning and end of the procedure.	90 minutes
Free Cortisol	Free cortisol will be collected from serum at the beginning and end of the procedure.	Baseline
Free Cortisol	Free cortisol will be collected from serum at the beginning and end of the procedure.	90 minutes
Cortisone	Cortisone will be collected from serum at the beginning and end of the procedure.	Baseline
Cortisone	Cortisone will be collected from serum at the beginning and end of the procedure.	90 minutes
Adrenocorticotropic Hormone	Adrenocorticotropic Hormone (ACTH) will be collected from serum at the beginning and end of the procedure.	Baseline
Adrenocorticotropic Hormone	Adrenocorticotropic Hormone (ACTH) will be collected from serum at the beginning and end of the procedure.	90 minutes
Glucose	Glucose will be collected from serum at the beginning and end of the procedure.	Baseline
Glucose	Glucose will be collected from serum at the beginning and end of the procedure.	90 minutes
Glucagon	Glucagon will be collected from serum at the beginning and end of the procedure.	Baseline
Glucagon	Glucagon will be collected from serum at the beginning and end of the procedure.	90 minutes
Insulin	Insulin will be collected from serum at the beginning and end of the procedure.	Baseline
Insulin	Insulin will be collected from serum at the beginning and end of the procedure.	90 minutes
Leptin	Leptin will be collected from serum at the beginning and end of the procedure.	Baseline
Leptin	Leptin will be collected from serum at the beginning and end of the procedure.	90 minutes
Ghrelin	Ghrelin will be collected from serum at the beginning and end of the procedure.	Baseline
Ghrelin	Ghrelin will be collected from serum at the beginning and end of the procedure.	90 minutes
Neuropeptide Y	Neuropeptide Y (NPY) will be collected from serum at the beginning and end of the procedure.	Baseline
Neuropeptide Y	Neuropeptide Y (NPY) will be collected from serum at the beginning and end of the procedure.	90 minutes
Glucagon-like peptide-1	Glucagon-like peptide-1 (GLP-1) will be collected from serum at the beginning and end of the procedure.	Baseline
Glucagon-like peptide-1	Glucagon-like peptide-1 (GLP-1) will be collected from serum at the beginning and end of the procedure.	90 minutes

Collaborators and Investigators

• Sponsor: Yale University
• Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Investigators: Principal Investigator: Robert M Sherwin, MD, Yale University

Study record dates

Study Major Dates

• Study Start: May 1, 2016
• Primary Completion (Actual): July 19, 2017
• Study Completion (Actual): July 19, 2017

Study Registration Dates

• First Submitted: March 22, 2016
• First Submitted That Met QC Criteria: March 22, 2016
• First Posted (Estimate): March 29, 2016

Study Record Updates

• Last Update Posted (Actual): May 25, 2022
• Last Update Submitted That Met QC Criteria: May 18, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Keywords: fMRI obesity
• Additional Relevant MeSH Terms: Overnutrition; Nutrition Disorders; Overweight; Body Weight; Obesity; Anti-Inflammatory Agents; Hydrocortisone
• Other Study ID Numbers: 1510016716; 2R01DK020495-42 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED