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RHYTHM (Formerly Escape II Myocardium) (RHYTHM)

Primary Purpose

Rheumatoid Arthritis

Status

Completed

Phase

Phase 4

Locations

United States

Study Type

Interventional

Intervention

TNF inhibitors

DMARDs

About this trial

This is an interventional prevention trial for Rheumatoid Arthritis focused on measuring Rheumatoid Arthritis, Cardiovascular disease, Myocardium, TNF-alpha inhibitors, ESCAPE, Co-morbidities, RHYTHM

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

Columbia University Medical Center

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Active Comparator

No Intervention

Arm Label

Patients - DMARDs + TNF Inhibitors

Patients - DMARDs only

Healthy Volunteers

Arm Description

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.

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

Subjects without RA who will function as controls.

Outcomes

Primary Outcome Measures

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."

Secondary Outcome Measures

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

This is designed to measure the myocardial inflammation, and its association with change in CDAI, after ramp-up of RA therapy over 6 months. Measurements are taken at baseline and 6-months post treatment escalation. Myocardial FDG uptake is classified as "diffuse" or "focal."

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

This is designed to evaluate the baseline characteristics of the entire RA cohort to understand the association of myocardial inflammation measure by FDG uptake with measures of left ventricular (LV) structure measured by 2D/3D echocardiogram at the baseline visit.

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

This is designed to evaluate the baseline characteristics of the entire RA cohort to understand the association of myocardial inflammation measure by FDG uptake with measures of left ventricular (LV) function measured by 2D/3D echocardiogram at the baseline visit.

Full Information

NCT ID

NCT01548768

First Posted

March 6, 2012

Last Updated

November 4, 2020

Sponsor

Columbia University

Collaborators

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

1. Study Identification

Unique Protocol Identification Number

NCT01548768

Brief Title

RHYTHM (Formerly Escape II Myocardium)

Acronym

RHYTHM

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.

Study Type

Interventional

2. Study Status

Record Verification Date

November 2020

Overall Recruitment Status

Completed

Study Start Date

October 10, 2011 (Actual)

Primary Completion Date

September 2019 (Actual)

Study Completion Date

September 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Columbia University

Collaborators

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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).

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Rheumatoid Arthritis

Keywords

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

7. Study Design

Primary Purpose

Prevention

Study Phase

Phase 4

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

149 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Patients - DMARDs + TNF Inhibitors

Arm Type

Experimental

Arm Description

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.

Arm Title

Patients - DMARDs only

Arm Type

Active Comparator

Arm Description

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

Arm Title

Healthy Volunteers

Arm Type

No Intervention

Arm Description

Subjects without RA who will function as controls.

Intervention Type

Drug

Intervention Name(s)

TNF inhibitors

Other Intervention Name(s)

Anti-TNF drugs

Intervention Description

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.

Intervention Type

Drug

Intervention Name(s)

DMARDs

Other Intervention Name(s)

Disease-modifying antirheumatic drugs

Intervention Description

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

Primary Outcome Measure Information:

Title

Number of Participants With Myocardial FDG Uptake

Description

Time Frame

Baseline

Secondary Outcome Measure Information:

Title

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

Description

Time Frame

Baseline, 6-Month Follow-up

Title

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

Description

Time Frame

Baseline

Title

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

Description

This is designed to evaluate the baseline characteristics of the entire RA cohort to understand the association of myocardial inflammation measure by FDG uptake with measures of left ventricular (LV) function measured by 2D/3D echocardiogram at the baseline visit.

Time Frame

Baseline

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Joan M Bathon, MD

Organizational Affiliation

Columbia University

Official's Role

Principal Investigator

Facility Information:

Facility Name

Columbia University Medical Center

City

New York

State/Province

New York

ZIP/Postal Code

10032

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

30407745

Citation

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.

Results Reference

result

Links:

URL

http://www.rheumatologyatcolumbia.org/

Description

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RHYTHM (Formerly Escape II Myocardium)

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