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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified September 2009 by Oklahoma Medical Research Foundation.
Recruitment status was  Recruiting
Sponsor:
Collaborator:
Wyeth is now a wholly owned subsidiary of Pfizer
Information provided by:
Oklahoma Medical Research Foundation
ClinicalTrials.gov Identifier:
NCT00987831
First received: September 30, 2009
Last updated: NA
Last verified: September 2009
History: No changes posted
  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 Patients will enter the trial in mild-moderate flare, be treated with depomedrol, and background treatments will be withdrawn.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at entry on various medications will be compared to biomarkers after steroid efficacy with background medications withdrawn.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

Resource links provided by NLM:


Further study details as provided by Oklahoma Medical Research Foundation:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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
Other: Blood drawing only
No treatments will be given
Other Name: No intervention
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:
  • Azathioprine is also known as Imuran
  • Depomedrol is sometimes called medrol or methylprednisolone
Active Comparator: Methotrexate and depomedrol
Methotrexate will be withdrawn and the procedures will be the same as the azathioprine arm
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
Active Comparator: Mycophenolate mofetil and depomedrol
Mycophenolate will be withdrawn and procedures will be the same as the other two active comparator arms.
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
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00987831

Contacts
Contact: Fredonna Carthen 405-271-7805 fredonna-carthen@omrf.org
Contact: Joe Rawdon, RN, NS 405-271-7805 joe-rawdon@omrf.org

Locations
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         
Sponsors and Collaborators
Oklahoma Medical Research Foundation
Wyeth is now a wholly owned subsidiary of Pfizer
Investigators
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:
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 August 01, 2014