Pharmacogenomics of the Variability in the In Vivo Response to Glucocorticoids

Study Overview
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Brief Summary
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This study evaluates the effect of acute administration of oral prednisone in white blood cells counts and glucose tolerance and the relationship of these measures with changes in gene expression in healthy volunteers. White blood cells counts, glucose tolerance and gene expression will be study before and after prednisone administration.

Detailed Description
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Prednisone is a potent anti-inflammatory drug that has large variability in its response. The large inter individual variability in the response to prednisone has a genetic component, but the genetic determinants of this variability remain unknown. We propose to use two relevant phenotypes, changes in white blood cell counts and changes in glucose tolerance induced by in vivo administration of prednisone, to characterize gene expression patterns and identify variants that are involved in the in vivo response to prednisone.

Official Title
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Pharmacogenomics of the Variability in the In Vivo Response to Glucocorticoids

Conditions
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Glucocorticoids Toxicity, Glucose Intolerance

Intervention / Treatment
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* Drug: Prednisone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 to 45 years old (to exclude the effect of age on glucose tolerance); BMI between 20 and 25 kg/m2 (to exclude individuals that are likely to have impaired insulin response); Normal fasting glucose; Stable weight for three months before participation Exclusion Criteria: BMI >25kg/m2; Fasting glucose ≥126 mg/dl Shift work or disordered sleep (to exclude individuals with alterations in the hypothalamus-adrenergic axis); Any diseases; Use of any medication regularly (including over-the-counter); Previous exposure to glucocorticoids (within the last year); Pregnancy

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: Other
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Prednisone<br>Each participant will received a single dose of oral 60 mg of prednisone Visit 1: Baseline Oral Glucose Tolerance Test (OGTT) and White Blood Count (WBC) count Visit 2: Prednisone 60mg oral at 7am, OGGT and WBC count at 4 to 8 hours post drug | Drug: Prednisone<br>* Prednisone 60 mg tablet once<br>* Other names: generic, not applicable;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| White Blood Cell Counts | White Blood Count at baseline (Visit 1) and within 4 to 8 hours after drug administration (Visit 2) | baseline and within 4 and 8 hours after drug administration | 
| Glucose Tolerance Test: Area Under the Curve (AUC) for Plasma Glucose | AUC for plasma glucose during glucose tolerance test at baseline and 4-8 hours after drug administration. Plasma glucose levels were measured at 0, 10, 20, 30, 60, 90 and 120 minutes during glucose tolerance test at baseline (Visit 1) and after drug administration (Visit 2) | baseline and 4-8 hours after drug administration | 
| Glucose Tolerance Test: Area Under the Curve (AUC) for Insulin Levels | AUC for insulin levels during glucose tolerance test at baseline and 4-8 hours after prednisone. Insulin levels were measured at 0, 10, 20, 30, 60, 90 and 120 minutes during glucose tolerance test at baseline (Visit 1) and after drug administration administration (Visit 2). | baseline and 4-8 hours after drug administration | 
| Glucose Tolerance Test: Area Under the Curve (AUC) for C-peptide Levels | AUC for C-peptide during glucose tolerance test at baseline and 4-8 hours after prednisone. C-peptide levels were measured at 0, 10, 20, 30, 60, 90, and 120 minutes during glucose tolerance test at baseline (Visit 1) and after drug administration (Visit 2) | baseline and 4-8 hours after drug administration | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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glucocorticoids, efficacy, metabolic toxicity