Glucocorticoids Toxicity, Glucose Intolerance
Conditions
Keywords
glucocorticoids, efficacy, metabolic toxicity
Brief summary
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
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.
Interventions
DRUGPrednisone
Prednisone 60 mg tablet once
Sponsors
National Institute of General Medical Sciences (NIGMS)
Vanderbilt University Medical Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| White Blood Cell Counts | baseline and within 4 and 8 hours after drug administration | White Blood Count at baseline (Visit 1) and within 4 to 8 hours after drug administration (Visit 2) |
| Glucose Tolerance Test: Area Under the Curve (AUC) for Plasma Glucose | baseline and 4-8 hours after drug administration | 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) |
| Glucose Tolerance Test: Area Under the Curve (AUC) for Insulin Levels | baseline and 4-8 hours after drug administration | 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). |
| Glucose Tolerance Test: Area Under the Curve (AUC) for C-peptide Levels | baseline and 4-8 hours after drug administration | 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) |
Countries
United States
Participant flow
Pre-assignment details
25 participants signed consent, 5 did not show up for screening and 2 failed screening. 18 participants started the study.
Participants by arm
| Arm | Count |
|---|---|
| Prednisone Each participant will received a single dose of oral 60 mg of prednisone
Prednisone: Prednisone 60 mg tablet once | 18 |
| Total | 18 |
Baseline characteristics
| Characteristic | Prednisone |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 18 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 17 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants |
| Race (NIH/OMB) More than one race | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 14 Participants |
| Region of Enrollment United States | 18 participants |
| Sex: Female, Male Female | 9 Participants |
| Sex: Female, Male Male | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 18 |
| other Total, other adverse events | 4 / 18 |
| serious Total, serious adverse events | 0 / 18 |
Outcome results
Primary
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
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Prednisone | Glucose Tolerance Test: Area Under the Curve (AUC) for C-peptide Levels | Visit 1: baseline | 493.89 ng*min/mL | Standard Deviation 135.77 |
| Prednisone | Glucose Tolerance Test: Area Under the Curve (AUC) for C-peptide Levels | Visit 2: 4-8 hours post prednisone | 449.41 ng*min/mL | Standard Deviation 101.27 |
Primary
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
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Prednisone | Glucose Tolerance Test: Area Under the Curve (AUC) for Insulin Levels | Visit 1: baseline | 5415.87 μU*min/mL | Standard Deviation 2344.63 |
| Prednisone | Glucose Tolerance Test: Area Under the Curve (AUC) for Insulin Levels | Visit 2: 4-8 hours post prednisone | 5466.55 μU*min/mL | Standard Deviation 2382.49 |
Primary
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
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Prednisone | Glucose Tolerance Test: Area Under the Curve (AUC) for Plasma Glucose | Visit 1: baseline | 13530.56 mg*min/dL | Standard Deviation 2002.23 |
| Prednisone | Glucose Tolerance Test: Area Under the Curve (AUC) for Plasma Glucose | Visit 2: 4-8 hours post prednisone | 20273.75 mg*min/dL | Standard Deviation 3973.26 |
Primary
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
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Prednisone | White Blood Cell Counts | Visit 1: baseline | 5.26 x10^3 cells/mL | Standard Deviation 0.92 |
| Prednisone | White Blood Cell Counts | Visit 2: 4 to 8 hours post prednisone | 6.99 x10^3 cells/mL | Standard Deviation 1.39 |