RHYTHM (Formerly Escape II Myocardium)

Columbia University

Status and phase

Completed

Phase 4

Conditions

Rheumatoid Arthritis

Treatments

Drug: DMARDs

Drug: TNF inhibitors

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT01548768

AAAI1026

7R01AR050026-07 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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).

Full 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.

Enrollment

149 patients

Sex

All

Ages

18+ years old

Volunteers

Accepts Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose

Prevention

Allocation

Non-Randomized

Interventional model

Parallel Assignment

Masking

None (Open label)

149 participants in 3 patient groups

Patients - DMARDs + TNF Inhibitors

Experimental group

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.

Treatment:

Drug: TNF inhibitors

Drug: DMARDs

Patients - DMARDs only

Active Comparator group

Description:

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

Treatment:

Drug: DMARDs

Healthy Volunteers

No Intervention group

Description: