Genomic Responses of Human Immune and Non-Immune Cells to Glucocorticoids

NCT02798523 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: 16012616-I-0126
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 1

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.

Conditions

Normal Physiology

Keywords

Methylprednisolone; Immunologic; Glucocorticoids; Functional genomics; RNA; Steroids

Outcome Measures

Primary Outcomes (1)

• Number of Participants Sampled for RNA-seq Differential Expression Analysis (Biological Replicates)

  Number of participants (biological replicates) that were successfully sampled for RNA-seq differential gene expression analysis in glucocorticoid-treated immune cells. The analysis employed a cutoff value of \< 5% false-discovery rate (FDR) to select the transcripts that were considered differentially expressed at each time point. The resulting gene lists were contrasted to determine which genes were uniquely differentially expressed in different cell types.

  Up to 2 or 4 hours post infusion depending on group

Study Arms (2)

Up to 2 hours post infusion

EXPERIMENTAL

Healthy volunteers received a single intravenous dose of 250 mg of methylprednisolone and blood was collected between one to two hours after the start of the infusion.

Drug: Methylprednisolone sodium succinate(Solu-Medrol)

Up to 4 hours post infusion

EXPERIMENTAL

Healthy volunteers received a single intravenous dose of 250 mg of methylprednisolone and blood was collected between two hours to four hours after the start of the infusion.

Drug: Methylprednisolone sodium succinate(Solu-Medrol); Drug: Topical methylprednisolone (Advantan emulsion 0 /1%)

Interventions

Methylprednisolone sodium succinate(Solu-Medrol) DRUG

Methylprednisolone sodium succinate for injection, USP (SOLU-MEDROL sterile powder, Pfizer, Inc.) is an anti-inflammatory glucocorticoid which occurs as a white, or nearly white, odorless hygroscopic, amorphous solid. It is very soluble in water and in alcohol; it is insoluble in chloroform and is very slightly soluble in acetone. 125-milligram Act-O-Vial (AOV) System: Each 2 mL AOV (when mixed) contains methylprednisolone sodium succinate equivalent to 125 milligrams methylprednisolone; also 1.6 mg monobasic sodium phosphate anhydrous; and 17.4 mg dibasic sodium phosphate dried.

Up to 2 hours post infusion; Up to 4 hours post infusion

Topical methylprednisolone (Advantan emulsion 0 /1%) DRUG

1 g Advantan emulsion 0.1% (Bayer) contains methylprednisolone aceponate (21-acetoxy-11beta-hydroxy-6alpha-methyl-17-propionyloxy-1,4-pregnadiene-3,20-dione) 1 mg, as the active ingredient. It is an oil-in-water emulsion containing medium chain triglycerides, caprylic-capric-stearic triglyceride, polyoxyethylene alcohol 2-stearyl ether, polyoxyethylene alcohol-21-stearyl ether, benzyl alcohol, disodium edetate, glycerol, and purified water.

Up to 4 hours post infusion

Eligibility Criteria

• Age: 18 Years - 64 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Age 18 to 64 years
• Willingness to have samples stored for future research
• Willingness to undergo genetic testing

You may not qualify if:

• Body Mass Index less than 18 or greater than 35
• Difficult peripheral venous access (as determined by study staff at screening)
• History of severe allergic reaction to glucocorticoids
• History of autoimmune or autoinflammatory disease
• Active solid or hematologic malignancy
• History of a skin condition (such as psoriasis, pemphigus, or atopic dermatitis) that could affect the results of the transcriptional analysis of the skin biopsy samples
• Diabetes mellitus
• Cancer chemotherapy within the past 5 years
• Surgery within the past 8 weeks
• History of recent (within the past 30 days) infection
• A positive test for human immunodeficiency virus, or hepatitis A, B or C virus infection (viral markers hepatitis screen, which includes HBsAg, anti-HCV IgG, anti-HAV IgM).
• A positive or indeterminate test for latent tuberculosis (interferon gamma release assay)
• History of parasitic, amebic, fungal or mycobacterial infections, or other possible latent infections
• Coagulation test (PT and PTT) results outside of normal range
• History of a bleeding disorder

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Publications (4)

• Khoury P, Stokes K, Gadkari M, Makiya MA, Legrand F, Hu Z, Klion A, Franco LM. Glucocorticoid-induced eosinopenia in humans can be linked to early transcriptional events. Allergy. 2018 Oct;73(10):2076-2079. doi: 10.1111/all.13497. Epub 2018 Jul 17. No abstract available.

  PMID: 29885264 BACKGROUND

• Franco LM, Gadkari M, Howe KN, Sun J, Kardava L, Kumar P, Kumari S, Hu Z, Fraser IDC, Moir S, Tsang JS, Germain RN. Immune regulation by glucocorticoids can be linked to cell type-dependent transcriptional responses. J Exp Med. 2019 Feb 4;216(2):384-406. doi: 10.1084/jem.20180595. Epub 2019 Jan 23.

  PMID: 30674564 BACKGROUND

• Gadkari M, Makiya MA, Legrand F, Stokes K, Brown T, Howe K, Khoury P, Hu Z, Klion A, Franco LM. Transcript- and protein-level analyses of the response of human eosinophils to glucocorticoids. Sci Data. 2018 Dec 4;5:180275. doi: 10.1038/sdata.2018.275.

  PMID: 30512017 BACKGROUND

• Hong SG, Sato N, Legrand F, Gadkari M, Makiya M, Stokes K, Howe KN, Yu SJ, Linde NS, Clevenger RR, Hunt T, Hu Z, Choyke PL, Dunbar CE, Klion AD, Franco LM. Glucocorticoid-induced eosinopenia results from CXCR4-dependent bone marrow migration. Blood. 2020 Dec 3;136(23):2667-2678. doi: 10.1182/blood.2020005161.

  PMID: 32659786 DERIVED

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Interventions

Methylprednisolone

Intervention Hierarchy (Ancestors)

Prednisolone; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Results Point of Contact

• Title: Dr. Luis Franco
• Organization: National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

luis.franco@nih.gov

+1 240 220 4366

Study Officials

• Luis M Franco, M.D.

  National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SEQUENTIAL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 10, 2016
• First Posted: June 14, 2016
• Study Start: January 24, 2017
• Primary Completion: May 31, 2022
• Study Completion: November 14, 2022
• Last Updated: June 22, 2023
• Results First Posted: June 22, 2023

Record last verified: 2022-11-14

Locations

US (1)