AzTrials
AzTrials

Systemic Lupus Erythematous (SLE)Early Phase 1NCT04233164

Genomic Effects of Glucocorticoids in Patients With Systemic Lupus Erythematosus

A Early Phase 1 study testing Solu-Medrol 1mg/kg and Solu-Medrol 250 mg in people with Systemic Lupus Erythematous (SLE), run by National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 to 80 years
Conditions the study is for
Systemic Lupus Erythematous (SLE)
What is being tested?
Solu-Medrol 1mg/kg and Solu-Medrol 250 mg
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
47 participants
Where
1 siteUnited States
Study dates
4 Mar 2020to 3 May 2022
Phase
Early Phase 1
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 80 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
Show all 9Show fewer
  • 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.
  • 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.

Who cannot join

  • 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.
Show all 24Show fewer
  • 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%.
  • A previously established diagnosis of diabetes mellitus or a fasting blood glucose level greater than or equal to 125 mg/dL at the time of screening. For patients without a previously established diagnosis of diabetes mellitus and a fasting blood glucose level < 125 mg/dL at the time of screening, no additional screening tests (e.g., HbA1c or oral glucose tolerance test) will be performed. A history of glucocorticoid-induced hyperglycemia that is not present at the time of screening in the absence of treatment will not be considered an exclusion criterion.
  • 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.
  • Use of one of the following CYP3A4 inhibitors in the 30 days prior to screening: clarithromycin, itraconazole, or ketoconazole.
  • Use of belimumab or rituximab within the past 180 days.
  • Vaccination within the past 30 days.
  • Pregnancy, current or in the 90 days prior to screening.
  • Currently breastfeeding.
  • Any electrocardiogram (ECG) abnormality that is clinically significant.
  • Any condition that, in the opinion of the investigator, contraindicates participation in this study.
  • Laboratory evaluations that will be used to establish eligibility are listed in sections 6 and 7, below. For exclusion criteria that involve previously established diagnoses, such as active malignancy, osteoporosis, or diabetes mellitus, any previously obtained diagnostic studies will be considered, but diagnostic testing for the sole purpose of establishing eligibility will not be performed.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • National Institutes of Health Clinical Center

    Bethesda, Maryland, 20892

Other trials in United States

About this study

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.

Read more

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.

Read the detailed description

Study Design:

This is a study of the acute effects of glucocorticoids on the immune system of patients with SLE. Participants will undergo baseline blood collection prior to receiving a single intravenous (IV) dose of methylprednisolone sodium succinate. Participants will be randomized into 1 of 2 dose groups: 1 mg/kg or 250 mg. Blood will be collected again at 2 and 4 hours after the methylprednisolone infusion. Individual participation requires 2 visits to the NIH CC and 2 follow-up phone calls. Total length of individual subject participation including screening is 1-12 weeks. Blood samples will be processed for isolation of hematopoietic cell sub-populations (eg, neutrophils, B cells, plasmacytoid dendritic cells, CD4+ T cells, CD8+ T cells, monocytes, and natural killer cells). Laboratory studies will be performed on the purified cells, with the goal of understanding the human response to glucocorticoids in vivo at the level of circulating cell populations (eg, flow cytometry, mass cytometry), RNA (eg, RNA sequencing [RNA-seq], small-RNA-seq, real-time polymerase chain reaction [PCR]), DNA (eg, chromatin immunoprecipitation sequencing [ChIP-seq], methylation analysis, DNA sequencing, genotyping), and protein (eg, flow cytometry, mass spectrometry). At each time point, serum methylprednisolone levels will be measured.

Study Agent/ Intervention Description:

A single IV infusion of methylprednisolone sodium succinate at either 1 mg/kg or 250 mg.

Primary Objective:

To understand the cellular and molecular response to glucocorticoids in individuals with SLE.

Glucocorticoid Genomics in SLE

Secondary Objectives:

  1. To identify candidate targets for therapeutic interventions that could mimic the action of glucocorticoids in patients with SLE, without the significant toxicity caused by the broad range of glucocorticoid actions.
  2. To test whether the transcriptional response to glucocorticoids differs between the two doses being studied.
  3. To identify similarities and differences, at baseline and in response to glucocorticoids, between the transcriptome of cells from patients and those from the previously studied healthy subjects.

Primary Endpoint:

A list of human protein-coding genes and non-coding RNAs that are differentially expressed in response to glucocorticoids in patients with SLE, for each of the studied cell types and doses.

Secondary Endpoints:

  1. A comparison of the transcriptional response to glucocorticoids between the two dose groups.
  2. A list of protein-coding and non-coding transcripts, their corresponding proteins, and the molecular pathways representing the best candidates for targeted therapeutic alternatives to glucocorticoids.
  3. Validation of the targets identified by functional studies.
  4. For each cell type, a list of protein-coding or non-coding transcripts that are shared and a list of transcripts that are different, between patients with SLE and the previously studied healthy controls, at baseline or in response to glucocorticoids.
Being tested
Solu-Medrol 1mg/kg, Solu-Medrol 250 mg
Keywords
Immunosuppressive Drugs, Methylprednisolone, PREDNISONE, Steroids, Autoimmunity
Medical subject headings
Autoimmune Diseases

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Solu-Medrol 1mg/kgDrug

    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.

  • Solu-Medrol 250 mgDrug

    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.

Study groups in NCT04233164
Study groupRoleWhat they receive
Group A: Glucocorticoids 1 mg/kg doseExperimentalParticipants 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.
Receives: Drug: Solu-Medrol 1mg/kg
Group B: Glucocorticoids 250 mg doseExperimentalParticipants 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.
Receives: Drug: Solu-Medrol 250 mg

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 2 hours and 4 hours post infusion

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted18 Jan 2020
  2. Study start4 Mar 2020
  3. Primary completion3 May 2022
  4. Study completion3 May 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Early Phase 1
Primary purpose
Basic science
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
47 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04233164
Sponsor's protocol ID
200032
Other IDs
20-AR-0032
Status last verified
Mar 2024
First submitted
16 Jan 2020
Last updated
6 Aug 2024
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No: Human data generated in this study will be shared for future research as follows: * De-identified data in an NIH-funded or approved public repository. Gene expression data will be made available through the Gene Expression Omnibus and Sequence Read Archive repositories. * De-identified data in public repositories. * Identifiable data in the Biomedical Translational Research Information System (BTRIS, automatic for activities in the CC) or the Genomic Research Integration System (GRIS). * De-identified or identifiable data with approved outside collaborators under appropriate agreements. * In publications and/or public presentations.

Publications

  • 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.

    PubMed 30674564

  • 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.

    PubMed 28192415

  • 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.

    PubMed 18762788

Questions about this trial

What is this clinical trial studying?

A Early Phase 1 study testing Solu-Medrol 1mg/kg and Solu-Medrol 250 mg in people with Systemic Lupus Erythematous (SLE), run by National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 6 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 21 Aug 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of SLE Patients That Were Sampled for RNA-seq Differential Expression Analysis (Biological Replicates) (time frame: 2 hours and 4 hours post infusion). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04233164, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Aug 2024.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in