Clinical trial NCT00361634: Dynamic Contrast-Enhanced Magnetic Resonance Imaging (DCE-MRI) to Measure Response to Etanercept in Rheumatoid Arthritis
Official title: DCE-MRI of the Wrist to Measure Short-Term Responses in Rheumatoid Arthritis Subjects Treated With Etanercept
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Rheumatoid Arthritis
Keywords: Etanercept
Enbrel
DCE-MRI
RA
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2006-08-08
Enrollment: 14
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to assess whether DCE-MRI can detect changes of active disease in rheumatoid arthritis (RA) patients after 4, 8 and 12 weeks of etanercept.

Detailed description: The current literature shows the promise of magnetic resonance imaging (MRI) for assessing response to therapy in RA but the heterogeneity of the methodology and the semi-quantitative nature of the image analysis limits its applicability. To evaluate the ability of DCE-MRI to serve as a biomarker for treatment-induced changes in RA associated synovial inflammation, the reproducibility of the measurement and an effect size are required. Additional endpoints such as synovial volume, bone erosion progression and bone marrow edema-like changes may also prove useful for short-term assessment of a therapeutic intervention, but have not been explored in the context of a pharmacodynamic biomarker. It is therefore critical to conduct a carefully designed longitudinal study, focused on identifying the key parameters related to the instrumentation and data analysis, to fully evaluate the potential utility of MRI in an early clinical development setting. Importantly, this study will also demonstrate the feasibility of using DCE-MRI at multiple centers to acquire useful information that will drive program decisions.

Expanded Access: Amgen provides expanded access for this clinical trial. Contact the Amgen Call Center (866-572-6436) for more information.

Eligibility criteria: Inclusion Criteria:

* Fulfillment of the 1987 American College of Rheumatology (ACR) criteria for RA with a disease duration \> 6 months
* Presence of active disease (defined as both tender and swollen joints) in at least one wrist
* Sub-optimal response to methotrexate (MTX) defined by the presence of the following criteria (based on 68/66 joint count): 8 or more swollen joints AND 8 or more tender joints (with involvement of the wrist, fingers and at least one region outside the hands) at screening
* Must be receiving MTX at a stable dose \> 15 mg/week at least 12 weeks prior to baseline
* a lower dose is acceptable if otherwise not tolerated (toxicity documentation required).

Exclusion Criteria:

* Patients who are currently receiving disease modifying anti-rheumatic drug (DMARD) therapy (other than MTX, hydroxychloroquine or sulfasalazine) including tumor necrosis factor (TNF) antagonists (etanercept, infliximab, and adalimumab), abatacept, rituximab, leflunomide, cyclosporine, and gold (oral and intramuscular injection) within 8 weeks or 5.5 half-lives, whichever is longer, of screening
* Co-existing condition requiring medications that alter vascular flow (e.g., nitrates, calcium channel blockers, ergot containing drugs) \[Potential effects of antihypertensive and migraine medications will be discussed with the Sponsor\]
* Comorbid autoimmune disorders including systemic lupus erythematosus
* Unable to undergo an MRI examination (e.g., presence of a pacemaker, defibrillator, or other implanted device such as anterior interbody cages, aneurysm clip or pedicle screws
* allergic to contrast agent
* tattoos \[in area of examination if contains metallic pigment\])
* or will likely require sedation for the procedure

Primary outcomes:
measure: Percent Change in Synovial Transfer Constant (Ktrans) From Days 1-29
timeFrame: Day 1 to Day 29
measure: Percent Change in Synovial Transfer Constant (Ktrans) From Days 1-57
timeFrame: Day 1 to Day 57
measure: Percent Change in Synovial Transfer Constant (Ktrans) From Days 1-85
timeFrame: Day 1 to Day 85
measure: Percent Change in Synovial Initial Area Under the (Contrast-time) Curve (IAUC) From Days 1-29
timeFrame: Day 1 to Day 29
measure: Percent Change in the Synovial Initial Area Under the Contrast-Tme Curve (IAUC) From Days 1-57
timeFrame: Day 1 to Day 57
measure: Percent Change in the Synovial Initial Area Under the Contrast-Time Curve (IAUC) From Days 1-85
timeFrame: Day 1 to Day 85
Secondary outcomes:
measure: Percent Change in Synovial Volume From Days 1-29
timeFrame: Day 1 to Day 29
measure: Percent Change in Synovial Volume From Days 1-57
timeFrame: Day 1 to Day 57
measure: Percent Change in Synovial Volume From Days 1-85
timeFrame: Day 1 to Day 85
measure: Difference Between Percent Change in Ktrans From Days -28 to 1 and Days 1 to 29
timeFrame: Day -28 to Day 29
measure: Difference Between Percent Change in Ktrans From Days -28 to 1 and Days 1 to 57
timeFrame: Day -28 to Day 57
measure: Difference Between Percent Change in Ktrans From Days -28 to 1 and Days 1 to 85
timeFrame: Day -28 to Day 85
measure: Difference Between Percent Change in IAUC From Days -28 to 1 and Days 1 to 29
timeFrame: Day -28 to Day 29
measure: Difference Between Percent Change in IAUC From Days -28 to 1 and Days 1 to 57
timeFrame: Day -28 to Day 57
measure: Difference Between Percent Change in IAUC From Days -28 to 1 and Days 1 to 85
timeFrame: Day -28 to Day 85
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Research Site
state: California
city: Seattle
country: United States
facility: Research Site
state: Washington
city: London
country: United Kingdom
facility: Research Site
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References: