Genomic Responses of Human Immune and Non-Immune Cells to Glucocorticoids
Condition: Normal Physiology
Intervention: Methylprednisolone sodium succinate(Solu-Medrol); Topical methylprednisolone (Advantan emulsion 0 /1%)
Intervention description: 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.; 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.
Intervention MeSH terms: Methylprednisolone; Methylprednisolone Acetate; Methylprednisolone Hemisuccinate; Prednisolone; Prednisolone acetate; Methylprednisolone aceponate; Prednisolone hemisuccinate; Prednisolone phosphate
Phase: Phase 1
Study type: Interventional
Primary purpose: Basic Science
Allocation: Non-Randomized
Intervention model: Sequential Assignment
Masking: None (Open Label)
Enrollment: 33.0
Sex: All
Minimum age: 18 Years
Maximum age: 64 Years
Healthy volunteers: No
Keywords: Methylprednisolone; Immunologic; Glucocorticoids; Functional genomics; RNA; Steroids

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.
    

Eligibility 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 malignancy

          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