Pharmacogenomics of the Variability in the In Vivo Response to Glucocorticoids

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.

Study Overview

• Status: Completed
• Conditions: Glucose Intolerance; Glucocorticoids Toxicity
• Intervention / Treatment: Drug: Prednisone

Detailed Description

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
• Enrollment (Actual): 25
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Vanderbilt University Medical Center -CRC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Prednisone; 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; Prednisone 60 mg tablet once; Other Names: generic, not applicable

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Vanderbilt University Medical Center
• Collaborators: National Institute of General Medical Sciences (NIGMS)
• Investigators: Principal Investigator: Vivian K Kawai, Vanderbilt University Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): February 15, 2017
• Primary Completion (Actual): January 10, 2019
• Study Completion (Actual): December 31, 2019

Study Registration Dates

• First Submitted: January 12, 2017
• First Submitted That Met QC Criteria: January 13, 2017
• First Posted (Estimate): January 18, 2017

Study Record Updates

• Last Update Posted (Actual): June 4, 2020
• Last Update Submitted That Met QC Criteria: May 25, 2020
• Last Verified: May 1, 2020

More Information

Terms related to this study

• Keywords: efficacy; glucocorticoids; metabolic toxicity
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Hyperglycemia; Glucose Intolerance; Physiological Effects of Drugs; Anti-Inflammatory Agents; Antineoplastic Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Prednisone
• Other Study ID Numbers: 161942 (Other Identifier: IND); 5K23GM117395-03 (U.S. NIH Grant/Contract)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No