Biomarkers of Lupus Disease: Serial Biomarker Sampling in Patients With Active Systemic Lupus Erythematosus (SLE) (BOLD)
Recruitment status was Recruiting
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Purpose
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 Patients will enter the trial in mild-moderate flare, be treated with depomedrol, and background treatments will be withdrawn.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at entry on various medications will be compared to biomarkers after steroid efficacy with background medications withdrawn.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.
| Condition | Intervention |
|---|---|
|
Systemic Lupus Erythematosus |
Drug: Depomedrol Other: Blood drawing only Drug: Methotrexate and depomedrol Drug: Mycophenolate mofetil and depomedrol |
| Study Type: | Interventional |
| Study Design: | Allocation: Non-Randomized Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Diagnostic |
| 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 |
- 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 [ Time Frame: 3-12 months (time of flare after first treatment with depomedrol) ] [ Designated as safety issue: Yes ]
- Biomarkers of steroid efficacy and toxicity [ Time Frame: 3-12 months ] [ Designated as safety issue: Yes ]
- validation of disease activity and flare instruments in development [ Time Frame: 3-12 months ] [ Designated as safety issue: No ]
- Patient reported outcomes and validation of new lupus specific quality of life and patient reported outcome measures [ Time Frame: 3-12 months ] [ Designated as safety issue: No ]
| Estimated Enrollment: | 50 |
| Study Start Date: | May 2009 |
| Estimated Study Completion Date: | December 2010 |
| Estimated Primary Completion Date: | November 2010 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
No Intervention: Blood drawing only
Healthy controls, age, sex and ethnicity matched to the active study participants will be recruited for one time blood donation as controls for the biomarker studies
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Other: Blood drawing only
No treatments will be given
Other Name: No intervention
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Active Comparator: Azathioprine and depomedrol
It is expected that about a third of patients will enter on azathioprine. When depomedrol is given, azathioprine will be stopped and biomarkers studied before and after this change. Depomedrol is expected to last 1-3 months, serial biomarkers will be drawn until time of any 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 but will be considered completers as defined by the protocol at this endpoint
|
Drug: Depomedrol
Patients entering on azathioprine will have this treatment stopped and depomedrol 160 mg IM will be given. If not better in two days this treatment can be repeated. Over two weeks a maximum of four such treatments can be elected in order to ensure symptom remission. If the intervention is ineffective, the patient will be withdrawn from study as an induction failure, and treated as appropriate. Subject would then be replaced by a new volunteer.
Other Names:
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Active Comparator: Methotrexate and depomedrol
Methotrexate will be withdrawn and the procedures will be the same as the azathioprine arm
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Drug: Methotrexate and depomedrol
Patients enter on methotrexate. Depomedrol 160 mg IM will be given and methotrexate withdrawn. Repeat dosing of depomedrol can be elected identically to the azathioprine arm
Other Name: methotrexate is also known as Rheumatrex
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Active Comparator: Mycophenolate mofetil and depomedrol
Mycophenolate will be withdrawn and procedures will be the same as the other two active comparator arms.
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Drug: Mycophenolate mofetil and depomedrol
Patients entering on mycophenolate will have this treatment withdrawn and depomedrol 160 mg IM will be given. Repeat depomedrol can be elected identically to the other active comparator arms
Other Name: Cellcept, Myfortic
|
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.
Eligibility| Ages Eligible for Study: | 15 Years to 70 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | Yes |
Inclusion Criteria:
Active Groups:
- ACR criteria for SLE.
- At least two organ systems moderately active to a minimum of BILAG B or SLEDAI score of 6.
Control group:
- Age, ethnicity and gender matched (2:1) with an active trial participant.
- Free of active or major chronic disease and taking no immune suppressive or anti-inflammatory medications.
Exclusion Criteria:
- Safety or circumstantial reasons why volunteer cannot comply with the protocol.
Contacts and Locations| Contact: Fredonna Carthen | 405-271-7805 | fredonna-carthen@omrf.org |
| Contact: Joe Rawdon, RN, NS | 405-271-7805 | joe-rawdon@omrf.org |
| United States, Oklahoma | |
| Oklahoma Medical Research Foundation | Recruiting |
| Oklahoma City, Oklahoma, United States, 73104 | |
| Contact: Fredonna Carthen 405-271-7805 fredonna-carthen@omrf.org | |
| Contact: Joy Hutcheson, RN 405-271-7805 joy-hutcheson@omrf.org | |
| Principal Investigator: Joan T Merrill, M.D. | |
| Sub-Investigator: Ewa Olech, M.D. | |
| Sub-Investigator: Joe Rawdon, RN, NS | |
| Sub-Investigator: Craig Davis, MD | |
| Principal Investigator: | Joan T Merrill | Oklahoma Medical Research Foundation |
More Information
No publications provided
| Responsible Party: | Joan T. Merrill, M.D. (PI), Oklahoma Medical Research Foundation |
| ClinicalTrials.gov Identifier: | NCT00987831 History of Changes |
| Other Study ID Numbers: | OMRF 09-02 |
| Study First Received: | September 30, 2009 |
| Last Updated: | September 30, 2009 |
| Health Authority: | United States: Institutional Review Board |
Keywords provided by Oklahoma Medical Research Foundation:
|
SLE lupus biomarkers |
depomedrol flare disease activity |
Additional relevant MeSH terms:
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Lupus Erythematosus, Systemic Connective Tissue Diseases Autoimmune Diseases Immune System Diseases Azathioprine Methotrexate Mycophenolate mofetil Methylprednisolone Hemisuccinate Prednisolone Mycophenolic Acid Methylprednisolone acetate Prednisolone acetate Methylprednisolone Prednisolone hemisuccinate Prednisolone phosphate |
Antimetabolites Molecular Mechanisms of Pharmacological Action Pharmacologic Actions Antimetabolites, Antineoplastic Antineoplastic Agents Therapeutic Uses Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Antirheumatic Agents Abortifacient Agents, Nonsteroidal Abortifacient Agents Reproductive Control Agents Dermatologic Agents Enzyme Inhibitors |
ClinicalTrials.gov processed this record on May 16, 2013