RHYTHM (Formerly Escape II Myocardium)

NCT01548768 | Completed Phase 4 Results DMC FDA Drug

• 2 other identifiers: AAAI10267R01AR050026-07
• Study Type: interventional
• Target: 149
• Locations: 1 country
• Sites: 1

Brief Summary

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).

Conditions

Rheumatoid Arthritis

Keywords

Rheumatoid Arthritis; Cardiovascular disease; Myocardium; TNF-alpha inhibitors; ESCAPE; Co-morbidities; RHYTHM

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Myocardial FDG Uptake

  This is designed to evaluate the baseline characteristics of the cross sectional RA cohort to understand the correlation of disease activity measured by the Clinical Disease Activity Index (CDAI) with myocardial inflammation measured by fluorodeoxyglucose (FDG) uptake in positron emission tomography (PET) scan at the baseline visit. Myocardial FDG uptake is classified as "diffuse" or "focal."

  Baseline

Secondary Outcomes (3)

• Number of Participants With Myocardial FDG Uptake After Escalation of RA Pharmacotherapy

  Baseline, 6-Month Follow-up

• LV Structure (Mean EDVI) in Association With Myocardial FDG Uptake

  Baseline

• LV Function (Mean Stroke Volume Index) in Association With Myocardial FDG Uptake

  Baseline

Study Arms (3)

Patients - DMARDs + TNF Inhibitors

EXPERIMENTAL

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; Drug: DMARDs

Patients - DMARDs only

ACTIVE COMPARATOR

Patients will receive their current treatment in an open label protocol in the context of standard of care.

Drug: DMARDs

Healthy Volunteers

NO INTERVENTION

Subjects without RA who will function as controls.

Interventions

TNF inhibitors DRUG

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.

Also known as: Anti-TNF drugs

Patients - DMARDs + TNF Inhibitors

DMARDs DRUG

Standard of care treatment for RA, such as Methotrexate or other disease-modifying antirheumatic drugs.

Also known as: Disease-modifying antirheumatic drugs

Patients - DMARDs + TNF Inhibitors; Patients - DMARDs only

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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):
• Age\>18 years old

Sponsors & Collaborators

• Columbia University: lead
• National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS): collaborator

Study Sites (1)

Columbia University Medical Center

New York, New York, 10032, United States

Location

Related Publications (1)

• Amigues I, Tugcu A, Russo C, Giles JT, Morgenstein R, Zartoshti A, Schulze C, Flores R, Bokhari S, Bathon JM. Myocardial Inflammation, Measured Using 18-Fluorodeoxyglucose Positron Emission Tomography With Computed Tomography, Is Associated With Disease Activity in Rheumatoid Arthritis. Arthritis Rheumatol. 2019 Apr;71(4):496-506. doi: 10.1002/art.40771. Epub 2019 Feb 28.

  PMID: 30407745 RESULT

Related Links

• Click here for information about this study

MeSH Terms

Conditions

Arthritis, Rheumatoid; Cardiovascular Diseases

Interventions

Tumor Necrosis Factor Inhibitors; Antirheumatic Agents

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)

Anti-Inflammatory Agents; Therapeutic Uses; Pharmacologic Actions; Chemical Actions and Uses

Results Point of Contact

• Title: Dr. Joan Bathon, MD
• Organization: Columbia University Irving Medical Center

jmb2311@cumc.columbia.edu

212-305-6327

Study Officials

• Joan M Bathon, MD

  Columbia University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor Medicine, Rheumatology

Study Record Dates

• First Submitted: March 6, 2012
• First Posted: March 8, 2012
• Study Start: October 10, 2011
• Primary Completion: September 1, 2019
• Study Completion: September 1, 2019
• Last Updated: November 27, 2020
• Results First Posted: November 27, 2020

Record last verified: 2020-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)