Escape II Myocardium
|First Received Date ICMJE||March 6, 2012|
|Last Updated Date||January 14, 2013|
|Start Date ICMJE||October 2011|
|Estimated Primary Completion Date||October 2015 (final data collection date for primary outcome measure)|
|Current Primary Outcome Measures ICMJE
|Original Primary Outcome Measures ICMJE||Same as current|
|Change History||Complete list of historical versions of study NCT01548768 on ClinicalTrials.gov Archive Site|
|Current 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 ]|
|Original Secondary Outcome Measures ICMJE||Same as current|
|Current Other Outcome Measures ICMJE||Not Provided|
|Original Other Outcome Measures ICMJE||Not Provided|
|Brief Title ICMJE||Escape II Myocardium|
|Official Title ICMJE||ESCAPE II MYOCARDIUM: How Rheumatoid Arthritis (RA) and Tumor Necrosis Factor (TNF) Inhibitors Affect the Myocardial Structure and Function.|
Data on a small number of patients with Rheumatoid Arthritis (RA) show that patients with RA may have a smaller heart size and altered heart function. There is limited evidence that general inflammation due to RA and inflammation within the heart may lead to a smaller heart size which may precede heart failure in RA. Preliminary data show that all these may improve with treatment with a specific class of medications called Tumor Necrosis Factor (TNF) inhibitors. The investigators hypothesize that RA affects the size and function of the heart via inflammation and that treatment with TNF inhibitors may improve the heart size and function and possibly prevent the development of heart failure in RA.
In order to investigate these hypotheses the investigators are going to identify 50 patients who have joint inflammation that has not responded to treatment with methotrexate. As it would happen under standard of care (even without participation in the study) these patients will receive additional treatment to control their joint disease. The investigators will randomly assign these patients to receive one of two equivalent treatments that are commonly prescribed in clinical practice and in the context of standard of care: either a TNF inhibitor OR the medications sulfasalazine and hydroxychloroquine will be added to methotrexate after randomization. It is known that these two different treatments are equivalent in controlling joint inflammation but is not known if one or the other has a more favorable effect on the heart size and function. The patients will be evaluated at baseline and return 6 months after randomization and will have imaging of their heart with PET scanning and echocardiogram at both time points. Participants will also provide information about their RA, other diseases and will offer blood for testing. The investigators assume (hypothesize) that patients randomly assigned to TNF inhibitor will have improved heart size and better heart function and less inflammation in the heart compared to patients assigned to take the oral medications sulfasalazine and hydroxychloroquine.
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. We have observed in few patients with RA that when they received treatment with medications called TNF inhibitors (in order to control the joint inflammation) their heart size and strength improved along with the improvement in their joint inflammation. 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. Some studies have shown 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 expand on the evidence suggesting that TNF inhibitors may be beneficial in terms of heart disease risk and heart function. We are going to only enroll patients with RA who do not have any prior heart disease. Specifically we are going to enroll 50 patients who have active joint disease and have not responded to treatment with methotrexate. These patients will be evaluated at baseline and 6 months later after randomization to different therapies. Normally, even if these patients did not participate in this ( or any) study, would have to take an additional medication along with methotrexate. Among the FDA approved options most rheumatologists would choose to add a TNF inhibitor to Methotrexate or proceed with what is called triple therapy (Methotrexate, Sulfasalazine, Plaquenil) . Both options are considered equivalent in terms of their ability to control joint inflammation. However nobody knows whether one or the other has a more beneficial influence on heart size function and degree of inflammation. We believe that TNF inhibitors will be more beneficial compared to triple therapy in terms of heart function.
In order to prove that the investigators are going randomly split the aforementioned 50 patients to receive one of the two treatments (TNF inhibitor vs triple therapy).
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 later 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 compare the two treatments and see whether TNF inhibitors truly have a beneficial effect on the heart function and how much more beneficial it is compared to triple therapy. A different effect of the two regimens 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 and also that the treatment will be randomly assigned.
Other 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 whether there is any differential effect between treatment with TNF inhibitors and triple therapy 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||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Outcomes Assessor)
Primary Purpose: Prevention
|Condition ICMJE||Rheumatoid Arthritis|
|Study Arm (s)||
|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||50|
|Estimated Completion Date||October 2015|
|Estimated Primary Completion Date||October 2015 (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||January 2013|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP