Dynamic Contrast-Enhanced Magnetic Resonance Imaging (DCE-MRI) to Measure Response to Etanercept in Rheumatoid Arthritis

NCT00361634 | Completed Phase 1 Results

• 1 other identifier: 20060118
• Study Type: interventional
• Target: 14
• Locations: 2 countries
• Sites: 3

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.

Conditions

Rheumatoid Arthritis

Keywords

Etanercept; Enbrel; DCE-MRI; RA

Outcome Measures

Primary Outcomes (6)

• Percent Change in Synovial Transfer Constant (Ktrans) From Days 1-29

  Percent change in transfer constant (Ktrans) for dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) of the wrist from study day 1 to study day 29. Ktrans reflects contrast delivery (capillary blood flow) and transport across the vascular endothelium (capillary permeability-surface area product), with the dominant factor depending on whether delivery is flow or permeability limited. A Ktrans value of zero indicates the absence of disease (ie, no leakage of the contrast agent into the synovial volume); therefore, an increase in this parameter indicates worsening disease (ie, greater permeability of the synovial membrane).

  Day 1 to Day 29

• Percent Change in Synovial Transfer Constant (Ktrans) From Days 1-57

  Percent change in transfer constant (Ktrans) for dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) of the wrist from study day 1 to study day 57. Ktrans reflects contrast delivery (capillary blood flow) and transport across the vascular endothelium (capillary permeability-surface area product), with the dominant factor depending on whether delivery is flow or permeability limited. A Ktrans value of zero indicates the absence of disease (ie, no leakage of the contrast agent into the synovial volume); therefore, an increase in this parameter indicates worsening disease (ie, greater permeability of the synovial membrane).

  Day 1 to Day 57

• Percent Change in Synovial Transfer Constant (Ktrans) From Days 1-85

  Percent change in transfer constant (Ktrans) for dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) of the wrist from study day 1 to study day 85. Ktrans reflects contrast delivery (capillary blood flow) and transport across the vascular endothelium (capillary permeability-surface area product), with the dominant factor depending on whether delivery is flow or permeability limited. A Ktrans value of zero indicates the absence of disease (ie, no leakage of the contrast agent into the synovial volume); therefore, increases in this parameter indicates worsening disease (ie, greater permeability of the synovial membrane).

  Day 1 to Day 85

• Percent Change in Synovial Initial Area Under the (Contrast-time) Curve (IAUC) From Days 1-29

  Percent change in the synovial initial area under the contrast-time curve (IAUC) for dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) of the wrist from Day 1 to Day 29. IAUC reflects the contrast distribution volume (extravascular extracellular space) in addition to contrast delivery and transport across the vascular endothelium. An IAUC value of zero indicates the absence of disease (ie, no leakage of the contrast agent into the synovial volume); therefore, an increase in this parameter indicates worsening disease (ie, greater permeability of the synovial membrane).

  Day 1 to Day 29

• Percent Change in the Synovial Initial Area Under the Contrast-Tme Curve (IAUC) From Days 1-57

  Percent change in the synovial initial area under the contrast-time curve (IAUC) for dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) of the wrist from Day 1 to Day 57. IAUC reflects the contrast distribution volume (extravascular extracellular space) in addition to contrast delivery and transport across the vascular endothelium. An IAUC value of zero indicates the absence of disease (ie, no leakage of the contrast agent into the synovial volume); therefore, an increase in this parameter indicates worsening disease (ie, greater permeability of the synovial membrane).

  Day 1 to Day 57

• Percent Change in the Synovial Initial Area Under the Contrast-Time Curve (IAUC) From Days 1-85

  Percent change in the synovial initial area under the contrast-time curve (IAUC) for dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) of the wrist from Day 1 to Day 85. IAUC reflects the contrast distribution volume (extravascular extracellular space) in addition to contrast delivery and transport across the vascular endothelium. An IAUC value of zero indicates the absence of disease (ie, no leakage of the contrast agent into the synovial volume); therefore, an increase in this parameter indicates worsening disease (ie, greater permeability of the synovial membrane).

  Day 1 to Day 85

Secondary Outcomes (9)

• Percent Change in Synovial Volume From Days 1-29

  Day 1 to Day 29

• Percent Change in Synovial Volume From Days 1-57

  Day 1 to Day 57

• Percent Change in Synovial Volume From Days 1-85

  Day 1 to Day 85

• Difference Between Percent Change in Ktrans From Days -28 to 1 and Days 1 to 29

  Day -28 to Day 29

• Difference Between Percent Change in Ktrans From Days -28 to 1 and Days 1 to 57

  Day -28 to Day 57

Study Arms (1)

Etanercept

EXPERIMENTAL

Etanercept 50 mg administered by subcutaneous injection once weekly for up to 12 weeks.

Drug: Etanercept

Interventions

Etanercept DRUG

Also known as: Enbrel®

Etanercept

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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

Sponsors & Collaborators

• Amgen: lead

Study Sites (3)

Research Site

Los Angeles, California, United States

Location

Research Site

Seattle, Washington, United States

Location

Research Site

London, United Kingdom

Location

Related Links

• AmgenTrials clinical trials website

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

Etanercept

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Immunoglobulin Fc Fragments; Immunoglobulin Fragments; Peptide Fragments; Peptides; Amino Acids, Peptides, and Proteins; Immunoglobulin Constant Regions; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Serum Globulins; Globulins; Receptors, Tumor Necrosis Factor; Receptors, Cytokine; Receptors, Immunologic; Receptors, Cell Surface; Membrane Proteins

Results Point of Contact

• Title: Study Director
• Organization: Amgen Inc.

866-572-6436

Study Officials

• MD

  Amgen

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Study Record Dates

• First Submitted: August 4, 2006
• First Posted: August 8, 2006
• Study Start: September 1, 2006
• Primary Completion: August 1, 2009
• Study Completion: March 1, 2010
• Last Updated: September 17, 2013
• Results First Posted: September 17, 2013

Record last verified: 2013-07

Locations

GB (1); US (2)