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RHYTHM (Formerly Escape II Myocardium) (RHYTHM)

This study is currently recruiting participants.
See Contacts and Locations
Verified March 2017 by Joan M. Bathon, Columbia University
Sponsor:
Collaborator:
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Information provided by (Responsible Party):
Joan M. Bathon, Columbia University
ClinicalTrials.gov Identifier:
NCT01548768
First received: March 6, 2012
Last updated: March 13, 2017
Last verified: March 2017
  Purpose

For aim 1, the proposed studies will be performed in 150 patients with RA and 25 subjects without RA (healthy volunteers) who will function as controls.

For aim 2, 25 of the patients enrolled in aim 1 (who are in need for further treatment due to increased RA activity despite their current treatment) will be recruited to continue in the study for an additional 24 (+/- 2) weeks (or 6 months). These patient will receive a TNF inhibitor in addition to their current treatment in an open label protocol for increased disease activity and in the context of standard of care.

The investigators hypothesize that anti-TNF agents in RA patients without heart disease will not adversely affect the heart (will not cause a detrimental change in heart structure or its function).


Condition Intervention Phase
Rheumatoid Arthritis Drug: TNF inhibitors Drug: DMARDs Phase 4

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: No masking
Primary Purpose: Prevention
Official Title: RHYTHM (RHeumatoid Arthritis studY of THe Myocardium): How Rheumatoid Arthritis (RA) and Tumor Necrosis Factor (TNF) Inhibitors Affect the Myocardial Structure and Function.

Resource links provided by NLM:


Further study details as provided by Joan M. Bathon, Columbia University:

Primary Outcome Measures:
  • Change in Left Ventricular mass [ Time Frame: Baseline, 6 months ]
    This is designed to evaluate the differential effect of TNF inhibitors vs triple therapy on Left Ventricular (LV) mass after 6 months of treatment for improvement.

  • Change in Left Ventricular Ejection Fraction [ Time Frame: Baseline, 6 months ]
    This is designed to evaluate Left Ventricular Ejection Fraction (LVEF) for improvement after 6 months of treatment.


Secondary Outcome Measures:
  • Change in the degree of myocardial inflammation [ Time Frame: Baseline, 6 months ]
    This is designed to evaluate the degree of myocardial inflammation as indicated by fluorodeoxyglucose (FDG) uptake in positron emission tomography (PET) scan.


Estimated Enrollment: 175
Actual Study Start Date: October 10, 2011
Estimated Study Completion Date: October 2018
Estimated Primary Completion Date: October 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Patients - DMARDs + TNF Inhibitors
Patients will receive a TNF inhibitor in addition to their current treatment in an open label protocol for increased disease activity and in the context of standard of care.
Drug: TNF inhibitors

TNF inhibitors are an FDA approved class of medications indicated for the treatment of RA when initial treatment (usually with methotrexate) has failed to achieve remission of RA disease activity. TNF inhibitors are part of the standard of care management of RA.

The possible TNF inhibitors are: Remicade, Humira, Enbrel, Cimzia, Simponi.

Other Name: Anti-TNF drugs
Drug: DMARDs
Standard of care treatment for RA, such as Methotrexate or other disease-modifying antirheumatic drugs.
Other Name: Disease-modifying antirheumatic drugs
Active Comparator: Patients - DMARDs only
Patients will receive their current treatment in an open label protocol in the context of standard of care.
Drug: DMARDs
Standard of care treatment for RA, such as Methotrexate or other disease-modifying antirheumatic drugs.
Other Name: Disease-modifying antirheumatic drugs
No Intervention: Healthy Volunteers
Subjects without RA who will function as controls.

Detailed Description:

Patients with Rheumatoid Arthritis (RA) have a shortened life expectancy compared to the general population. Cardiovascular disease (CVD), including heart failure (HF), is the primary cause of the extra deaths in RA. HF, in general, results from failure of the heart muscle to pump adequately. In other words the heart muscle in HF becomes "weak". In patients without RA, the heart muscle gets larger before symptoms of HF appear. Contrary to that, patients with RA have reduced heart size and reduced heart strength. This may mean that in RA the pathway to heart failure may be different compared to what happens in patients without RA. It is possible - for example - that in RA the heart muscle becomes smaller before it becomes weak (while in non-RA patients the heart muscle becomes larger before it becomes weak). It is possible that cells that create inflammation in the joints may also do the same in the heart muscle making it smaller, thinner and eventually weaker.

Patients with RA nowadays can be treated with a variety of medications for their joint inflammation. These medications are powerful and have reduced the risk of permanent joint damage and disability. However it is unknown what is the effect of these medications on the heart size and strength and whether they increase or decrease the risk for cardiovascular disease and heart failure.

Among the medications used for RA are medications called TNF inhibitors. They are usually prescribed to patients who have joint inflammation that has not responded to treatment with the first line medication Methotrexate. Data in non-RA patients with advanced heart failure suggest that anti-TNF agents may not help heart failure and may even be harmful. However, the effect of these agents on the hearts of RA patients has never been directly studied. Some observational studies suggest that RA patients treated with TNF inhibitors have a lower risk of developing heart disease. Overall the knowledge regarding the effect of TNF inhibitors on RA patients heart function is limited.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

For RA patients (150 patients):

INCLUSION CRITERIA

  • Diagnosis of Rheumatoid Arthritis by 2010 American College of Rheumatology (ACR) and the European League Against Rheumatism (EULAR) diagnostic criteria
  • Age>18 years old
  • Moderate to high RA disease activity defined by a Clinical Disease Activity Index (CDAI) of >10
  • Stable dose of Methotrexate for 6 weeks prior to enrollment
  • Stable doses of Nonsteroidal anti-inflammatory drug (NSAID) and prednisone (if already taking these medications) for 2 weeks prior to study

EXCLUSION CRITERIA

  • Prior self reported or physician diagnosed CV event (MI; angina; stroke or Transient Ischemic Attach (TIA); Heart Failure (HF); prior CV procedure (e.g., coronary artery bypass graft, angioplasty, valve replacement, pacemaker)
  • Contraindications to having a PET-CT scan or receive adenosine or Fludeoxyglucose (FDG)
  • Active treatment for Cancer
  • Uncontrolled hypertension
  • Diabetes
  • Smoking
  • Treatment with a TNF inhibitor or other biologic currently or within the last 6 months
  • Current treatment with "Triple Therapy" or within the last 2 months
  • Untreated positive purified protein derivative (PPD) tuberculosis skin test or active tuberculosis
  • History of Lymphoma and Melanoma
  • Ejection Fraction (EF) < 40% (if not known in advance then the Study Visit I Echocardiogram results will be used to exclude the patient from randomization and follow up)
  • Change in NSAID/Prednisone dosage in last 2 weeks
  • Participation in other research studies involving imaging/radiation exposure

For non-RA subjects (25 controls):

INCLUSION CRITERIA

  • Age>18 years old
  • Absence of diagnosis of RA

EXCLUSION CRITERIA

  • Prior self reported or physician diagnosed CV event (MI; angina; stroke or Transient Ischemic Attach (TIA); Heart Failure (HF); prior CV procedure (e.g., coronary artery bypass graft, angioplasty, valve replacement, pacemaker)
  • Contraindications to having a PET-CT scan or receive adenosine or FDG
  • Uncontrolled hypertension
  • Participation in other research studies involving imaging/radiation exposure
  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: NCT01548768

Contacts
Contact: Janine Rose, BS 2123054114 jr2780@cumc.columbia.edu
Contact: Afshin Zartoshti, MS 2123422751 az2200@cumc.columbia.edu

Locations
United States, New York
Columbia University Medical Center Recruiting
New York, New York, United States, 10032
Contact: Janine Rose    212-305-4114    jr2780@cumc.columbia.edu   
Contact: Afshin Zartoshti, MS    2123422751    az2200@cumc.columbia.edu   
Principal Investigator: Joan M Bathon, MD         
Sponsors and Collaborators
Columbia University
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Investigators
Principal Investigator: Joan M Bathon, MD Columbia University
  More Information

Additional Information:
Responsible Party: Joan M. Bathon, Professor Medicine, Rheumatology, Columbia University
ClinicalTrials.gov Identifier: NCT01548768     History of Changes
Other Study ID Numbers: AAAI1026
7R01AR050026-07 ( U.S. NIH Grant/Contract )
Study First Received: March 6, 2012
Last Updated: March 13, 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Joan M. Bathon, Columbia University:
Rheumatoid Arthritis
Cardiovascular disease
Myocardium
TNF-alpha inhibitors
ESCAPE
Co-morbidities
RHYTHM

Additional relevant MeSH terms:
Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Antirheumatic Agents

ClinicalTrials.gov processed this record on July 24, 2017