RHYTHM (Formerly Escape II Myocardium) (RHYTHM)

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2016 by 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: July 12, 2016
Last verified: July 2016
  Purpose

Anti-TNF drugs are a major class of treatment in patients with rheumatoid arthritis (RA). 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. However, observational studies suggest that anti-TNF agents may actually prevent the onset of heart failure in RA patients and may reduce hospitalizations in RA patients who have heart failure. 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).

In order to investigate these hypotheses, the investigators will identify 25 patients who have joint inflammation that have not responded adequately to treatment with methotrexate or other oral DMARDs . As would happen under standard of care (even without participation in the study) patients will receive additional treatment to control their joint disease. The investigators will assign these patients to be prescribed (in agreement with the patients and their Rheumatologists), a TNF inhibitor in addition to their current treatment.TNF inhibitors are an FDA approved treatment for management of RA and have been used by Rheumatologists for many years. At enrollment and 6 months after starting treatment patients will have imaging of their heart with PET-CT scanning and echocardiogram at both time points. Participants will also provide information about their RA and other medical conditions and blood will be drawn.


Condition Intervention
Rheumatoid Arthritis
Drug: TNF inhibitors

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
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 Columbia University:

Primary Outcome Measures:
  • Change in left ventricular mass [ Time Frame: 6 months after treatment with TNF inhibitors versus triple therapy ] [ Designated as safety issue: No ]
    We will evaluate the differential effect TNF inhibitors vs "triple therapy" on LV mass after 6 months of treatment for improvement.

  • Change in Left Ventricular Ejection Fraction [ Time Frame: After 6 months of treatment with TNF inhibitor versus triple therapy ] [ Designated as safety issue: No ]
    We will evaluate LVEF for improvement.


Secondary Outcome Measures:
  • Change in the degree of myocardial inflammation (as indicated by FDG uptake in PET scanning) [ Time Frame: 6 months after treatment with TNF inhibitor versus triple therapy ] [ Designated as safety issue: No ]

Estimated Enrollment: 25
Study Start Date: October 2011
Estimated Study Completion Date: October 2016
Estimated Primary Completion Date: October 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
TNF Inhibitors
Disease activity will be evaluated at the time of every visit.. At the time of the first safety visit, tolerability and safety will be evaluated. At the time of Safety Visit II if CDAI is still >10 (indicative of moderate disease activity) an increase in the dose or frequency of the TNF inhibitor (in the case of agents such as infliximab or adalimumab where escalation of dosage is an option) or a switch to treatment to an alternative TNF inhibitor will take place. Patients will return at 24 weeks for their Second Study Visit (Study Visit 2) for completion of the study and further management as per standard of care. An additional Safety Visit (Safety Visit 3) will take place at 32 weeks and will serve as an exit safety visit.
Drug: TNF inhibitors

Patients will receive one of the FDA approved TNF inhibitors at the approved dosage regimen.

Patients will be evaluated during safety visits scheduled every 8 weeks between the 0 and 6 month study visits. At the time of the first safety visit medication tolerability and safety will be evaluated. At the time of the second safety visit if joint disease activity is still moderate or high an increase in the dose or frequency of the TNF inhibitor or a switch to treatment to an alternative/equivalent TNF inhibitor will take place ( there are 5 TNF inhibitors approved at the moment).

Other Names:
  • Infliximab
  • Adalimumab
  • Etanercept
  • Certolizumab pegol
  • Golimumab
  • Remicade
  • Humira
  • Enbrel
  • Cimzia
  • Simponi

  Show Detailed Description

  Eligibility

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

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 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 (tuberculosis skin test) PPD 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 control participation (15 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 
Study First Received: March 6, 2012
Last Updated: July 12, 2016
Health Authority: United States: Institutional Review Board
United States: Food and Drug Administration

Keywords provided by 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
Adalimumab
Infliximab
Certolizumab Pegol
Anti-Inflammatory Agents
Antirheumatic Agents
Dermatologic Agents
Gastrointestinal Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on August 23, 2016