Genomic Effects of Glucocorticoids in Patients With Systemic Lupus Erythematosus

NCT04233164 | Completed Early Phase 1 Results FDA Drug

• 2 other identifiers: 20003220-AR-0032
• Study Type: interventional
• Target: 47
• Locations: 1 country
• Sites: 1

Brief Summary

Background: The immune system is the body's defense against bacteria and other harmful invaders. In people with systemic lupus erythematosus (SLE), the immune system becomes overactive and attacks healthy cells by mistake. Many people use glucocorticoids (GCs) to treat their SLE. GCs can calm down an overactive immune system by changing how the body reads genes. But GCs have side effects that can increase over time. Researchers want to learn more about how GCs work. This may help to develop new and better drugs for treating SLE without the side effects GCs have. Objective: To better understand how GCs affect the immune system in people with SLE. Eligibility: People age 18-80 with SLE. Design: Participants will be screened with a physical exam. They will have a health and medical history. They will have blood and urine tests. They will have an electrocardiogram to measure heart activity. For this, sticky pads are put on their chest, arms, and legs. Participants will have a methylprednisolone infusion for about 30 minutes. It will be given through a needle in a vein. Blood will be collected immediately before, 2 hours after, and 4 hours after the start of the infusion. Blood pressure and heart activity will be monitored. Participants will repeat some of the screening tests. Participants will be contacted twice in the week after the infusion visit. They will discuss any health problems they are having.

Conditions

Systemic Lupus Erythematous (SLE)

Keywords

Immunosuppressive Drugs; Methylprednisolone; PREDNISONE; Steroids; Autoimmunity

Outcome Measures

Primary Outcomes (1)

• Number of SLE Patients That Were Sampled for RNA-seq Differential Expression Analysis (Biological Replicates)

  Number of of SLE patients that were 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.

  2 hours and 4 hours post infusion

Study Arms (2)

Group A: Glucocorticoids 1 mg/kg dose

EXPERIMENTAL

Participants with Systemic Lupus Erythematosus (SLE) received a single intravenous dose of methylprednisolone 1 mg/kg and blood was collected two hours and four hours after the start of the infusion.

Drug: Solu-Medrol 1mg/kg

Group B: Glucocorticoids 250 mg dose

EXPERIMENTAL

Participants with Systemic Lupus Erythematosus (SLE) received a single intravenous dose of 250 mg of methylprednisolone and blood was collected two hours and four hours after the start of the infusion.

Drug: Solu-Medrol 250 mg

Interventions

Solu-Medrol 1mg/kg DRUG

Methylprednisolone sodium succinate for injection, United States Pharmacopeia grade (USP), sold as SOLU-MEDROL sterile powder by Pfizer, Inc, is an anti-inflammatory glucocorticoid that occurs as a white, or nearly white, odorless hygroscopic, amorphous solid. It is very soluble in water and in alcohol, but is insoluble in chloroform and is very slightly soluble in acetone. The study agent solution will be administered as an IV infusion over 30 minutes, for a total single dose of 1 mg/kg of methylprednisolone.

Group A: Glucocorticoids 1 mg/kg dose

Solu-Medrol 250 mg DRUG

Methylprednisolone sodium succinate for injection, United States Pharmacopeia grade (USP), sold as SOLU-MEDROL sterile powder by Pfizer, Inc, is an anti-inflammatory glucocorticoid that occurs as a white, or nearly white, odorless hygroscopic, amorphous solid. It is very soluble in water and in alcohol, but is insoluble in chloroform and is very slightly soluble in acetone. The study agent solution will be administered as an IV infusion over 30 minutes, for a total single dose of 250 mg of methylprednisolone.

Group B: Glucocorticoids 250 mg dose

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Aged 18-80 years.
• Has a diagnosis of SLE based on the 1997 Update of the 1982 American College of Rheumatology Revised Criteria for Classification of SLE.
• Currently enrolled in study 94-AR-0066.
• Able to provide informed consent.
• Willing to allow genetic testing.
• Has a primary care physician or other healthcare provider who will manage all health conditions related or unrelated to the study objectives.
• If receiving immunosuppressive therapies other than glucocorticoids for SLE, then on a stable dose (defined as no increases in dose for the 60 days prior to screening).
• A. If receiving glucocorticoid therapy and not experiencing a lupus flare at the time of the screening visit, then potential participants must be on a daily prednisone or prednisone-equivalent dose less than or equal to 10 mg/day and agree to undergo a glucocorticoid taper.
• B. If receiving glucocorticoid therapy experiencing a lupus flare at the time of the screening visit, then potential participants must be on a daily prednisone or prednisone-equivalent dose less than or equal to 15mg/day. A glucocorticoid taper will not be performed.

You may not qualify if:

• Body mass index (BMI) \< 18 or \> 40.
• History of a severe allergic reaction to glucocorticoids.
• History of a severe adverse cardiovascular or psychiatric event related to glucocorticoid administration.
• Use of a glucocorticoid at a prednisone-equivalent dose 10 mg/day in the 15 days prior to screening (\> 15 mg/day if experiencing a flare on the day of the screening visit).
• A previously established diagnosis of an active solid or hematologic malignancy.
• A previously established diagnosis of untreated osteoporosis. For the purpose of this study, osteoporosis is defined as a dual-energy X-ray absorptiometry (DEXA) scan obtained within 2 years of screening demonstrating a hip or spine bone mineral density T score less than or equal to -2.5 in men or greater than or equal to 50 in postmenopausal women.
• A previously established diagnosis of untreated osteopenia with a high fracture risk. For the purpose of this study, osteopenia is defined as a DEXA scan obtained within 2 years of screening demonstrating a hip or spine bone mineral density T score \< -1 and \> -2.5 in men or greater than or equal to 50 in postmenopausal women. For the purpose of this study, a high fracture risk is defined as a fracture risk assessment tool (FRAX) 10-year risk of major osteoporotic fracture \> 20%, or a FRAX 10-year risk of hip fracture \> 3%.
• Cancer chemotherapy within the 5 years prior to screening.
• Surgery requiring general anesthesia in the 8 weeks prior to screening.
• History of an infection requiring IV antibiotics in the 30 days prior to screening.
• A positive test for HIV or hepatitis A, B, or C virus infection.
• A positive or indeterminate test for active or latent tuberculosis (interferon gamma release assay \[IGRA\]) without evidence of prior treatment.
• History of chronic or possible latent untreated parasitic, amebic, fungal, or mycobacterial infections.
• Use of desmopressin in the 30 days prior to screening.
• Use of one of the following cytochrome P450 isozyme (CYP) 3A4 inducers in the 30 days prior to screening: nafcillin, rifabutin, rifampin, St. John s wort, or troglitazone.

Sponsors & Collaborators

• National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• 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

• Cain DW, Cidlowski JA. Immune regulation by glucocorticoids. Nat Rev Immunol. 2017 Apr;17(4):233-247. doi: 10.1038/nri.2017.1. Epub 2017 Feb 13.

  PMID: 28192415 BACKGROUND

• Stahn C, Buttgereit F. Genomic and nongenomic effects of glucocorticoids. Nat Clin Pract Rheumatol. 2008 Oct;4(10):525-33. doi: 10.1038/ncprheum0898. Epub 2008 Sep 2.

  PMID: 18762788 BACKGROUND

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Autoimmune Diseases

Interventions

Methylprednisolone Hemisuccinate

Condition Hierarchy (Ancestors)

Immune System Diseases

Intervention Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Franco, Luis
• Organization: National Inst of Arthritis and Musculoskeletal and Skin Diseases

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: early phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 16, 2020
• First Posted: January 18, 2020
• Study Start: March 4, 2020
• Primary Completion: May 3, 2022
• Study Completion: May 3, 2022
• Last Updated: August 6, 2024
• Results First Posted: August 21, 2023

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)