Pharmacogenomics of the Variability in the In Vivo Response to Glucocorticoids

Vanderbilt University Medical Center25 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

OTHER

Masking

NONE

Enrollment

Conditions

Glucocorticoids Toxicity Glucose Intolerance

Interventions

PrednisoneDRUG

Prednisone 60 mg tablet once

Eligibility

Sex: ALLMin age: 18 YearsMax age: 45 YearsHealthy volunteers:

Medical Language ↔ Plain English

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

Locations (1)

Vanderbilt University Medical Center -CRC

Nashville, Tennessee, United States

Outcomes

Primary Outcomes

White Blood Cell Counts

White Blood Count at baseline (Visit 1) and within 4 to 8 hours after drug administration (Visit 2)

Time frame: 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)

Time frame: 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).

Time frame: 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)

Time frame: baseline and 4-8 hours after drug administration

Data from ClinicalTrials.gov

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