Draining PLN and Synovial Inflammation in RA Knee Joints Pre and Post Anti-TNF or B Cell Depletion Therapy

NCT01083563 | Terminated

• 1 other identifier: RSRB-27325
• Study Type: observational
• Target: 7
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to examine the effect of anti-TNF therapy on rheumatoid arthritis using magnetic resonance imaging (MRI) and ultrasound imaging. Anti-TNF therapies include a group of medications such as Enbrel, Remicade and Humira that affect your body's inflammatory response. These medications are routinely prescribed for the treatment of rheumatoid arthritis.

Conditions

Rheumatoid Arthritis

Keywords

TNF; CD20; RA

Outcome Measures

Primary Outcomes (3)

• Morphologic and functional relationship between the draining PLN and synovial inflammation in the knee joints of RA patients

  To examine the morphologic and functional relationship between the draining PLN and synovial inflammation in the knee joints of RA patients before and after therapy with TNF antagonists or B cell depletion therapy via MRI and Doppler ultrasound.

  Week 0 (initial medication dose) and Week 8 (post medication dose)

• TNF inhibition on volume and CE in the PLN in RA patients by MRI versus Doppler ultrasound.

  To assess the effect of TNF inhibition on volume and CE in the PLN in RA patients by MRI, and compare the effectiveness of Doppler US to achieve the same outcome measures.

  Week 0 (initial medication dose) and Week 8 (post medication dose)

• Effect of anti-CD20 therapy on volume and CE in the PLN in RA patients who "flare"

  To assess the effect of anti-CD20 therapy on volume and CE in the PLN in RA patients who are experiencing knee synovitis after a period of effective anti-TNF therapy

  Week 0 (initial medication dose) and Week 8 (post medication dose)

Study Arms (2)

RA inadequate response to methotrexate

Individuals with rheumatoid arthritis who have had an inadequate response to methotrexate and will be starting on an anti-TNF agent.

RA inadequate response to anti-TNF.

Individuals with rheumatoid arthritis who have had an inadequate response to an anti-TNF and will be be given a rituximab infusion.

Eligibility Criteria

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

Study Population

Male and female RA sufferers not less than 18 yrs of age who are currently experiencing knee synovitis. Racial and ethnic origin of subjects will be monitored to reflect the diversity of our community.

You may qualify if:

• Signed, IRB-approved, written informed consent
• Subjects can be of either gender but must be more than 18 years old.
• Subjects must fulfill the disease activity criteria for RA and a DAS28 will be assessed at baseline and at 2 months after rituximab therapy.
• Aim A - Eligible subjects must meet criteria for RA and have an inadequate response to MTX defined as DAS28 \>5.1. They must have been on a steady dose of MTX (between 15 and 20 mg /week for a minimum of 8 weeks). Subjects must have evidence of knee synovitis on exam to enter the study.
• Aim B - Subjects must have demonstrated a response to a TNF antagonist as evidenced by a DAS score \<2.8 or \<4 tender and swollen joints. Flare will be defined as a DAS 28 \>5.1 of more than 8 swollen and tender joints. Subjects must have evidence of knee synovitis to enter the study. Subjects will be off etanercept, infliximab or adalimumab for 4 weeks before starting BCDT. All subjects must also be on a stable dose of DMARD (MTX, leflunomide, azulfidine, hydroxychloroquine) for 8 weeks before entry into the study.

You may not qualify if:

• Active systemic disorders or inflammatory conditions (i.e., chronic infection with hepatitis B, hepatitis C or HIV) other than the conditions being studied.
• Patients with a plasma creatinine \> 1.5 mg/dl
• Aim B - Subjects with an allergy to corticosteroids will be excluded from the study.
• Anyone answering yes to the following questions will be excluded:
• Do you have a history of:
• Cardiac (Heart) pacemaker or defibrillator?
• Cardiac (Heart) valve replacement or prosthesis?
• Aneurysm clips from brain surgery?
• Ear prosthesis (cochlear or stapedial implant)? (hearing aids?)
• Neurostimulator?
• Biostimulator?
• Any type of pumps in or on your body?
• Shrapnel, gunshot wound, BB pellet?
• Metallic penile prosthesis?
• Metallic blood vessel filter or stent?

Sponsors & Collaborators

• University of Rochester: lead

Study Sites (1)

University of Rochester

Rochester, New York, 14642, United States

Location

Related Publications (2)

• Rahimi H, Bell R, Bouta EM, Wood RW, Xing L, Ritchlin CT, Schwarz EM. Lymphatic imaging to assess rheumatoid flare: mechanistic insights and biomarker potential. Arthritis Res Ther. 2016 Sep 1;18:194. doi: 10.1186/s13075-016-1092-0.

  PMID: 27586634 DERIVED

• Li J, Zhou Q, Wood RW, Kuzin I, Bottaro A, Ritchlin CT, Xing L, Schwarz EM. CD23(+)/CD21(hi) B-cell translocation and ipsilateral lymph node collapse is associated with asymmetric arthritic flare in TNF-Tg mice. Arthritis Res Ther. 2011 Aug 31;13(4):R138. doi: 10.1186/ar3452.

  PMID: 21884592 DERIVED

MeSH Terms

Conditions

Arthritis, Rheumatoid

Condition Hierarchy (Ancestors)

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

Study Officials

• Christopher Ritchlin, MD / MPH

  University of Rochester

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: M.D., M.P.H., Professor of Medicine Allergy, Immunology & Rheumatology Division

Study Record Dates

• First Submitted: March 8, 2010
• First Posted: March 9, 2010
• Study Start: July 1, 2009
• Primary Completion: March 1, 2015
• Study Completion: March 1, 2015
• Last Updated: April 8, 2015

Record last verified: 2015-04

Locations

US (1)