Biomarkers of Lupus Disease: Serial Biomarker Sampling in Patients With Active Systemic Lupus Erythematosus (SLE)

Condition(s) targeted: Systemic Lupus Erythematosus

Intervention: Depomedrol (Drug); Blood drawing only (Other); Methotrexate and depomedrol (Drug); Mycophenolate mofetil and depomedrol (Drug)

Phase: N/A

Status: Recruiting

Sponsored by: Oklahoma Medical Research Foundation

Official(s) and/or principal investigator(s):
Joan T Merrill, Principal Investigator, Affiliation: Oklahoma Medical Research Foundation

Overall contact:
Fredonna Carthen, Phone: 405-271-7805, Email: fredonna-carthen@omrf.org

Hypothesis: A reason for repeated disappointing outcomes of clinical trials testing targeted immune biologics for lupus may be the heterogeneity of the disease, exacerbated by the variable effects on immune homeostasis of the background medications that must be continued, in most study designs, in these flare-prone patients.

Purpose of Study: This study will purposefully study a population equivalent to the placebo group of typical trials in SLE. Patients will enter the trial in mild-moderate flare, be treated with depomedrol, and background treatments will be withdrawn. Biomarkers at entry on various medications will be compared to biomarkers after steroid efficacy with background medications withdrawn. Depomedrol usually slowly wears off over one to three months. Patients will be closely observed, with serial biomarkers drawn at monthly intervals or, immediately at the time of a new flare. Those patients who do develop new flares during the course of the next year (maximal participation time) will donate blood samples for biomarkers (flaring on tapering or absent depomedrol effect) and will then be immediately treated as deemed appropriate, exiting the study. The study will end when 50 patients have met this endpoint. A control population of matched, healthy individuals will donate blood once for the same biomarker studies.

Official title: Biomarkers of Lupus Disease: Study of Biomarker Changes Before and After Treatment With Depomedrol and Background Medication Withdrawal in Patients With Mild to Moderate SLE Disease Activity

Study design: Allocation: Non-Randomized, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Diagnostic

Primary outcome: To determine major biomarker patterns in lupus patients flaring on minimal background medications and compare to those flaring on typical background meds used in clinic and clinical trials

Secondary outcome:

Biomarkers of steroid efficacy and toxicity

validation of disease activity and flare instruments in development

Patient reported outcomes and validation of new lupus specific quality of life and patient reported outcome measures

Detailed description: Patients with at least a SLEDAI score of 6 or a BILAG score of B in at least two organ systems or A in at least one organ system will be immediately entered into this study once informed consent is obtained. Background immune suppressants (if any) are stopped and in half of the patients hydroxychloroquine will also be stopped. All patients will immediately receive a shot of depomedrol 160 mg IM. Over the next two weeks they may elect up to three more shots of depomedrol for a total of four shots by the two week visit period. A complete battery of blood tests to assess lupus disease is drawn at the screening visit, and monthly thereafter. Biomarker studies are drawn as often as weekly for some markers and as often as three times in the study (landmark visits) for others.

Landmark visits are defined as: 1.) screening (pre-dose, on background meds with active disease) 2.) two weeks or four weeks after screening as optimal to assess a patient who has stopped background meds and is now maximally improved (but at least one grade drop in BILAG scores in all organs entered at A or B or a four point drop in SLEDAI, otherwise the participant is deemed a treatment failure and will be replaced in the study). 3.) Flare visit on no background immune suppression and 1/2 on no hydroxychloroquine either, defined as the monthly visit or interim visit at which the patient has an increase in SLEDAI of 4 points from maximal improvement or has increased back to at least two BILAG B scores or at least one BILAG A scores. Patients will be seen within 3 days if flare occurs between monthly scheduled visits.

The following biomarkers are being obtained: cytokine panel, B Cell studies, T Cell studies, autoantibody profiles, epigenetic and gene expression studies and flow cytometry studies.

Minimum age: 15 Years. Maximum age: 70 Years. Gender(s): Both.

Criteria:

Inclusion Criteria:

Active Groups:

1. ACR criteria for SLE.

2. At least two organ systems moderately active to a minimum of BILAG B or SLEDAI score of 6.

Control group:

1. Age, ethnicity and gender matched (2: 1) with an active trial participant.

2. Free of active or major chronic disease and taking no immune suppressive or anti-inflammatory medications.

Exclusion Criteria:

1. Safety or circumstantial reasons why volunteer cannot comply with the protocol.

Fredonna Carthen, Phone: 405-271-7805, Email: fredonna-carthen@omrf.org

Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma 73104, United States; Recruiting
Fredonna Carthen, Phone: 405-271-7805, Email: fredonna-carthen@omrf.org
Joy Hutcheson, RN, Phone: 405-271-7805, Email: joy-hutcheson@omrf.org
Joan T Merrill, M.D., Principal Investigator
Ewa Olech, M.D., Sub-Investigator
Joe Rawdon, RN, NS, Sub-Investigator
Craig Davis, MD, Sub-Investigator

Starting date: May 2009
Last updated: September 30, 2009