Biomarkers of Lupus Disease: Serial Biomarker Sampling in Patients With Active Systemic Lupus Erythematosus (SLE)
BOLD
2 other identifiers
interventional
158
1 country
2
Brief Summary
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 was designed to purposefully study a population equivalent to the placebo group of typical trials in SLE. In Group A patients entered the trial in mild-moderate flare, were treated with depomedrol, and any background immune suppressants withdrawn. Biomarkers at entry on various medications can be compared to biomarkers after steroid efficacy with background immune suppressants withdrawn. Depomedrol usually wears off over one to three months. Patients were closely observed, with serial biomarkers drawn at monthly intervals or immediately at the time of a new flare. Those patients developing new flares donated blood samples, were immediately treated as deemed appropriate, exiting the study. Group A was designed for up to 50 patients and recruited a total of 41. An additional group of 62 SLE patients donated blood once without additional interventions in order to increase the power of exploratory cross-sectional biomarker analysis on different immune suppressants (Group B). A control population of matched, healthy individuals donated blood twice for the same biomarker studies to validate these assays (Group C).
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started May 2009
Typical duration for phase_1
2 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
May 1, 2009
CompletedFirst Submitted
Initial submission to the registry
September 30, 2009
CompletedFirst Posted
Study publicly available on registry
October 1, 2009
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 1, 2012
CompletedStudy Completion
Last participant's last visit for all outcomes
December 1, 2012
CompletedResults Posted
Study results publicly available
October 20, 2014
CompletedOctober 20, 2014
October 1, 2014
3.6 years
September 30, 2009
August 28, 2013
October 17, 2014
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Time to Flare Comparing Patients With Moderate vs Severe Disease Activity at Baseline
Group A only: patients on immunosuppressive treatments had them withdrawn at baseline. All patients were allowed up to 160 mg depomedrol at baseline which could be repeated within two weeks up to a total of 4 shots maximum or until satisfactory improvement. Time to flare was calculated from baseline. moderate disease at baseline was defined as up to 3 BILAG B (moderate disease) organ scores, no BILAG A (severe disease) score and a SLEDAI \</= 10. Severe disease required \>3 BILAG B, OR at least one BILAG A OR SLEDAI \> 10 or meeting criteria for a severe flare on the SELENA SLEDAI flare index. At baseline 25 patients with moderate disease. 16 patients had severe disease. Note: severe rash with A on BILAG is only SLEDAI=2, explaining some discrepancies in measures
12 months
Study Arms (3)
Blood drawing only Group C
EXPERIMENTALHealthy controls, age, sex and ethnicity matched to the active study participants were recruited for two time blood donation as controls for the biomarker studies
Group A SLE prospective study
EXPERIMENTALIn Group A SLE patients enter with active disease. Any immune suppressant (e.g. methotrexate, azathioprine or mmf) is withdrawn and after blood drawing, depomedrol up to 160 mg IM is given. This may be repeated for a maximum of 160mg up to four times total in the first two weeks. Depomedrol is expected to last 1-3 months, serial biomarkers will be drawn until time of flare, at which time biomarkers will be drawn, patient is defined as meeting endpoint and new treatment initiated. Patients may elect to continue to donate blood samples per protocol up to one year.
Group B SLE one blood donation
EXPERIMENTALSLE patients who meet the same entry criteria as Group A could elect to donate blood one time and not to continue in the prospective protocol. No extra intervention was performed other than blood draw and medical records review. This allowed an extension of cross sectional comparisons between biomarker changes related to background treatments by combining Group A baseline data with Group B data.
Interventions
Blood drawing, history, physical examination,medical record review, questionnaires, completion of disease activity measures including SLEDAI,BILAG, CLASI,PGA,PROs,LFA investigational systems, BICLA, SRI
Blood drawing and Brief medical history to ensure status of healthy control
Patients have history and physical exmamination at each visit. Blood is drawn at each visit. At baseline, any background immune suppressant is stopped and patients given depomedrol up to 160 mg IM which can be repeated up to four times in the first two weeks. Patients are seen again at week 2, 4 and monthly until the final flare visit at which time they donate blood, receive appropriate treatments and exit study. Patients may elect to continue in study for up to one year. The following disease activity measures are included: SLEDAI, BILAG, CLASI, PGA, PROs (including lupus PRO and SF-36 ant ptGA), joint counts, exploratory outcome measures,BICLA,SRI
Eligibility Criteria
You may qualify if:
- SLE Groups (Group A and B):
- ACR criteria for SLE.
- At least two organ systems moderately active to a minimum of BILAG B or SLEDAI score of 6.
- Control group (Group C):
- Age, ethnicity and gender matched (2:1) with an SLE study participant.
- Free of active or major chronic disease as determined by brief history.
You may not qualify if:
- \. Safety or circumstantial reasons why volunteer cannot comply with the protocol.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Oklahoma Medical Research Foundationlead
- Pfizercollaborator
Study Sites (2)
Oklahoma Medical Research Foundation
Oklahoma City, Oklahoma, 73104, United States
Pfizer Inc
Collegeville, Pennsylvania, 19426, United States
Related Publications (1)
Merrill JT, Immermann F, Whitley M, Zhou T, Hill A, O'Toole M, Reddy P, Honczarenko M, Thanou A, Rawdon J, Guthridge JM, James JA, Sridharan S. The Biomarkers of Lupus Disease Study: A Bold Approach May Mitigate Interference of Background Immunosuppressants in Clinical Trials. Arthritis Rheumatol. 2017 Jun;69(6):1257-1266. doi: 10.1002/art.40086.
PMID: 28257602DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Joan T Merrill, M.D
- Organization
- Oklahoma Medical Research Foundation
Study Officials
- PRINCIPAL INVESTIGATOR
Joan T Merrill
Oklahoma Medical Research Foundation
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- LTE60
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Head, Clinical Pharmacology Research Program
Study Record Dates
First Submitted
September 30, 2009
First Posted
October 1, 2009
Study Start
May 1, 2009
Primary Completion
December 1, 2012
Study Completion
December 1, 2012
Last Updated
October 20, 2014
Results First Posted
October 20, 2014
Record last verified: 2014-10