Investigating the Central and Peripheral Mechanisms by Which Glucocorticoids Affect Hunger

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

Detailed Description
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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.

Official Title
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Investigating the Central and Peripheral Mechanisms by Which Glucocorticoids Affect Hunger

Conditions
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Obesity

Intervention / Treatment
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* Drug: hydrocortisone
* Other: saline


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intravenous glucocorticoids<br>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<br>* 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.<br>|
| Placebo Comparator: Intravenous saline<br>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<br>* Saline will be used as the placebo comparator. It will be administered in the same manner as the active drug.<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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fMRI obesity