Biomarkers of Lupus Disease: Serial Biomarker Sampling in Patients With Active Systemic Lupus Erythematosus (SLE)
| Status: | Completed |
|---|---|
| Conditions: | Lupus |
| Therapuetic Areas: | Immunology / Infectious Diseases |
| Healthy: | No |
| Age Range: | 15 - 70 |
| Updated: | 11/8/2014 |
| Start Date: | May 2009 |
| End Date: | December 2010 |
| Contact: | Fredonna Carthen |
| Email: | fredonna-carthen@omrf.org |
| Phone: | 405-271-7805 |
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
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treated with depomedrol, and background treatments will be withdrawn.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medications withdrawn.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.
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treated with depomedrol, and background treatments will be withdrawn.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.
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.
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.
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.
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