RHYTHM (Formerly Escape II Myocardium)
|First Received Date ICMJE||March 6, 2012|
|Last Updated Date||October 28, 2015|
|Start Date ICMJE||October 2011|
|Estimated Primary Completion Date||October 2016 (final data collection date for primary outcome measure)|
|Current Primary Outcome Measures ICMJE
|Original Primary Outcome Measures ICMJE
|Change History||Complete list of historical versions of study NCT01548768 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures ICMJE
||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 ]|
|Original Secondary Outcome Measures ICMJE
||Improvement 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 ]|
|Current Other Outcome Measures ICMJE||Not Provided|
|Original Other Outcome Measures ICMJE||Not Provided|
|Brief Title ICMJE||RHYTHM (Formerly Escape II Myocardium)|
|Official Title ICMJE||RHYTHM (RHeumatoid Arthritis studY of THe Myocardium): How Rheumatoid Arthritis (RA) and Tumor Necrosis Factor (TNF) Inhibitors Affect the Myocardial Structure and Function.|
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.
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, we found 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 we don't know 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 Rheumatoid Arthritis 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.. However when these medications were used in trials for the treatment of advanced heart failure in patients without RA they were not helpful and it was thought that they may be harmful. Although the effect of these drugs has not been directly studied in the hearts of RA patients, 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.
In this study the investigators propose to investigate whether TNF inhibitors are beneficial or not in terms of heart disease risk and heart function in patients with RA. We are going to only enroll patients with RA who do not have any prior heart disease. Specifically we are going to enroll 25 patients who have active joint disease and have not responded adequately to treatment with methotrexate or DMARD combination therapy. These patients will be evaluated at baseline and 6 months later after escalation to a TNF inhibitor. Normally, even if these patients did not participate in this (or any) study, they would have to take an additional medication along with methotrexate. The addition of a TNF inhibitor is one of the options for treatment of patients with inadequate response to MTX and other oral DMARDs. 25 patients will be enrolled and prescribed a TNF inhibitor in addition to their current treatment.
All these patients will come to our research facilities at Columbia university and will undergo a series of tests at baseline and 6 months later. These will include imaging of the heart with PET scanning and echocardiography. The latter will tell us the size of the heart muscle. The former will tell us how strongly the heart muscle pumps the blood. PET scanning can also quantify the degree of inflammation within the heart. Patients will complete questionnaires about their RA their other diseases, their quality of life. Their joints will be examined by a rheumatologist and patients will provide some blood for research and clinical tests.
These will allow the investigators to see whether TNF inhibitors have anyl effect on the heart function. This will allow us to understand how heart disease starts in RA, what is the role of inflammation and which inflammatory pathways are responsible for heart disease in patients with RA.
In between the two study visits the patients participating in the study will return every 6-8 weeks for what we call safety visits. During these visits they will be evaluated for the need to increase the dose of their medications or switched to a different but similar drug, they will be asked whether they can tolerate their drugs and in summary we will ensure their well-being and improvement of their joint inflammation. Overall this study will parallel/mirror what would happen even if the patients did not participate in research. The only difference from "real life clinical practice" is that the patients will have to undergo imaging and other research tests.
Other assessments pertinent to heart function evaluations will take place during this study such as weight measurement , blood pressure, heart rate, and a walk test.
In addition to the above: our previous studies have shown that RA patients have more fat than non RA individuals and that fat accumulates in the body in a different way than non RA people. This differential fat amount and distribution is thought to increase the amount of inflammation in the body and is thought to further increase the risk of heart disease in RA. In order to measure the amount of fat and how it is distributed across the body, patients will undergo whole body DEXA scans and three CT slices (two abdominal and one thigh), which will be obtained concurrently with the PET-CT imaging. Then these data will be analyzed in order to find out the effect of TNF inhibitors on fat distribution.
In order to be certain that the results of this study will not be the result of what is called random variation we are going to enroll 15 healthy subjects. These subjects will also be evaluated 6 months apart with the same evaluations mentioned above. Obviously the 15 healthy enrolled individuals will not receive any treatment. The results of heart imaging for these healthy participants will allow us to "standardize" the results for the RA patients enrolled.
|Study Type ICMJE||Interventional|
|Study Phase||Not Provided|
|Study Design ICMJE||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Prevention
|Condition ICMJE||Rheumatoid Arthritis|
|Intervention ICMJE||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).
|Study Arm (s)||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.
Intervention: Drug: TNF inhibitors
|Publications *||Not Provided|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Recruiting|
|Estimated Enrollment ICMJE||25|
|Estimated Completion Date||October 2016|
|Estimated Primary Completion Date||October 2016 (final data collection date for primary outcome measure)|
|Eligibility Criteria ICMJE||
For control participation (15 controls):
|Ages||18 Years and older|
|Accepts Healthy Volunteers||Yes|
|Listed Location Countries ICMJE||United States|
|Removed Location Countries|
|NCT Number ICMJE||NCT01548768|
|Other Study ID Numbers ICMJE||AAAI1026, 7R01AR050026-07|
|Has Data Monitoring Committee||Yes|
|Responsible Party||Joan M. Bathon, Columbia University|
|Study Sponsor ICMJE||Columbia University|
|Collaborators ICMJE||National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)|
|Information Provided By||Columbia University|
|Verification Date||October 2015|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP