Ignite Creation Date:
2024-05-06 @ 8:40 AM
Last Modification Date:
2024-10-26 @ 12:03 PM
Study NCT ID:
NCT02798523
Status:
COMPLETED
Last Update Posted:
2023-06-22
First Post:
2016-06-10
Brief Title:
Genomic Responses of Human Immune and Non-Immune Cells to Glucocorticoids
Sponsor:
National Institute of Allergy and Infectious Diseases NIAID
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
Genomic Response of Human Immune and Non-Immune Cells to Glucocorticoids
Status:
COMPLETED
Status Verified Date:
2022-11-14
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Background
The immune system defends the body against bacteria and other harmful invaders But it can overact and attack healthy cells by mistake The group of drugs called glucocorticoids GCs can calm down an overactive immune system But they often cause negative side effects Researchers want to learn how human genes respond to GCs Genes live inside each cell of the body They tell our cells how to function Researchers hope the results of this study will show them how to develop better drugs that will have the benefits of GCs without the side effects
Objectives
To study how human genes respond to glucocorticoid drugs
Eligibility
Healthy adult volunteers ages 18-64
Design
Participants will be screened with a medical history and physical exam They will have a heart test and blood tests
The study visit will last about 6 hours
Participants will have medical history physical exam and 3 blood draws
Participants will have a skin biopsy An injection will numb the skin on one arm Then a tool will remove a piece of skin about as big as a pencil eraser
A GC cream will be applied to the other arm
Participants will get the GC study drug for 30 minutes It will be a liquid that will drip through a needle placed in an arm vein
Participants will have a skin biopsy of the arm that had the cream applied
Participants will have follow-up calls 1 and 4 days later They will be asked about reactions or other health problems
The immune system defends the body against bacteria and other harmful invaders But it can overact and attack healthy cells by mistake The group of drugs called glucocorticoids GCs can calm down an overactive immune system But they often cause negative side effects Researchers want to learn how human genes respond to GCs Genes live inside each cell of the body They tell our cells how to function Researchers hope the results of this study will show them how to develop better drugs that will have the benefits of GCs without the side effects
Objectives
To study how human genes respond to glucocorticoid drugs
Eligibility
Healthy adult volunteers ages 18-64
Design
Participants will be screened with a medical history and physical exam They will have a heart test and blood tests
The study visit will last about 6 hours
Participants will have medical history physical exam and 3 blood draws
Participants will have a skin biopsy An injection will numb the skin on one arm Then a tool will remove a piece of skin about as big as a pencil eraser
A GC cream will be applied to the other arm
Participants will get the GC study drug for 30 minutes It will be a liquid that will drip through a needle placed in an arm vein
Participants will have a skin biopsy of the arm that had the cream applied
Participants will have follow-up calls 1 and 4 days later They will be asked about reactions or other health problems
Detailed Description:
Glucocorticoids are among the most frequently prescribed immunosuppressive and anti-inflammatory medications worldwide Long-term use however is complicated by serious non-immunologic side effects Ongoing in vitro experiments with human primary cells in our laboratory suggest that there are indeed fundamental differences in the genomic response of immune and non-immune cells to glucocorticoids These and other aspects of drug action at the genomic level have not been completely characterized This study will attempt to generate a list of human genes and non-coding RNAs that are differentially expressed and regulated in response to glucocorticoids between immune and non-immune cells These data will be used to identify transcripts their corresponding proteins and the molecular pathways that are best candidates for targeted intervention Potential targets could be validated with small interfering RNA siRNA libraries with the long-term goal of developing small-molecule or nanoparticle-facilitated RNA interference RNAi interventions that reproduce the therapeutic action of glucocorticoids in immune cells while avoiding their harmful side effects on other tissues
Healthy volunteers will undergo baseline blood collection prior to receiving a single intravenous dose of 250 milligrams of methylprednisolone sodium succinate Blood will be collected in one of two regimens 1 and 2 hours or 2 and 4 hours after the start of the infusion A skin punch biopsy may be obtained before healthy volunteers receive IV methylprednisolone If so topical methylprednisolone will be applied to a limited area of skin contralateral to the site of the baseline skin biopsy and an additional skin biopsy will be obtained 4 hours after drug administration from the area where topical methylprednisolone was applied Follow-up phone calls 1 day and 1 week after discharge will document any adverse effects related to the drug or skin biopsy Total length of individual study participation is 1-5 weeks
Blood samples will be processed for isolation of hematopoietic cell sub-population neutrophils B cells CD4 T cells CD8 T cells monocytes and natural killer NK cells Laboratory studies will be performed in the purified cells with the goal of understanding the human response to glucocorticoids in vivo at the level of RNA eg RNA sequencing small -RNA-sequencing real-time PCR DNA eg ChIP-seq methylation analysis DNA sequencing genotyping and protein eg flow cytometry mass spectrometry At each time point serum methylprednisolone levels will be measured and flow cytometry for standard lineage markers will be performed Skin biopsies will be subjected to RNA isolation for RNA sequencing and small-RNA sequencing A fragment of each skin biopsy will undergo fibroblast isolation and culture for in vitro exposure to glucocorticoids and for the generation of induced pluripotent stem iPS cells
Healthy volunteers will undergo baseline blood collection prior to receiving a single intravenous dose of 250 milligrams of methylprednisolone sodium succinate Blood will be collected in one of two regimens 1 and 2 hours or 2 and 4 hours after the start of the infusion A skin punch biopsy may be obtained before healthy volunteers receive IV methylprednisolone If so topical methylprednisolone will be applied to a limited area of skin contralateral to the site of the baseline skin biopsy and an additional skin biopsy will be obtained 4 hours after drug administration from the area where topical methylprednisolone was applied Follow-up phone calls 1 day and 1 week after discharge will document any adverse effects related to the drug or skin biopsy Total length of individual study participation is 1-5 weeks
Blood samples will be processed for isolation of hematopoietic cell sub-population neutrophils B cells CD4 T cells CD8 T cells monocytes and natural killer NK cells Laboratory studies will be performed in the purified cells with the goal of understanding the human response to glucocorticoids in vivo at the level of RNA eg RNA sequencing small -RNA-sequencing real-time PCR DNA eg ChIP-seq methylation analysis DNA sequencing genotyping and protein eg flow cytometry mass spectrometry At each time point serum methylprednisolone levels will be measured and flow cytometry for standard lineage markers will be performed Skin biopsies will be subjected to RNA isolation for RNA sequencing and small-RNA sequencing A fragment of each skin biopsy will undergo fibroblast isolation and culture for in vitro exposure to glucocorticoids and for the generation of induced pluripotent stem iPS cells
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 16-I-0126 | None | None | None |