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

• Status: Recruiting
• Trial end date: 2022-10-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Treatments: Glucocorticoids; Methylprednisolone; Methylprednisolone aceponate; Methylprednisolone Acetate; Methylprednisolone Hemisuccinate; Prednisolone; Prednisolone acetate; Prednisolone hemisuccinate; Prednisolone phosphate

Criteria

• INCLUSION CRITERIA:

1. Age 18 to 64 years

2. Willingness to have samples stored for future research

3. Willingness to undergo genetic testing

EXCLUSION CRITERIA:

1. Body Mass Index less than 18 or greater than 35

2. Difficult peripheral venous access (as determined by study staff at screening)

3. History of severe allergic reaction to glucocorticoids

4. History of autoimmune or autoinflammatory disease

5. Active solid or hematologic malgnancy

6. 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

7. Diabetes mellitus

8. Cancer chemotherapy within the past 5 years

9. Surgery within the past 8 weeks

10. History of recent (within the past 30 days) infection

11. 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).

12. A positive or indeterminate test for latent tuberculosis (interferon gamma release assay)

13. History of parasitic, amebic, fungal or mycobacterial infections, or other possible latent infections

14. Coagulation test (PT and PTT) results outside of normal range

15. History of a bleeding disorder

16. Use of a glucocorticoid (including topical or inhaled), a nonsteroidal anti-inflammatory drug (including aspirin), an anti-epileptic drug, an anticoagulant, a statin, fluoxetine, diltiazem, amiodarone, clarithromycin, ketoconazole, or St. John s wort, within the past 30 days

17. Vaccination within the past 30 days

18. Receipt of an immunosuppressant or immunomodulatory drug within the past 30 days

19. Pregnancy, current or within the past 90 days, or trying to become pregnant during the study

20. Current breastfeeding

21. Complete blood count (CBC) and/or acute care panel values are both outside of the NIH Department of Laboratory Medicine normal reference range and deemed clinically significant by the principal investigator

22. Any Electrocardiogram (ECG) abnormality that is clinically significant

23. Any condition that, in the investigator s opinion, may put the participant at undue risk or compromise the study s scientific objectives

24. Participation in a clinical protocol which includes an intervention that, in the opinion of the investigator, may affect the results of the current study