Rheumatoid ArthritisPhase 4RHYTHMNCT01548768
RHYTHM (Formerly Escape II Myocardium)
A Phase 4 study testing TNF inhibitors and DMARDs in people with Rheumatoid Arthritis, run by Columbia University at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Rheumatoid Arthritis
- What is being tested?
- TNF inhibitors and DMARDs
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 149 participants
- Where
- 1 siteUnited States
- Study dates
- 10 Oct 2011to Sep 2019
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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
- Age>18 years old
- Absence of diagnosis of RA
Who cannot join
- 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
Show all 18Show fewer
- 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):
- 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 locations and contacts
1 site in 1 country.
United States1 site
Columbia University Medical Center
New York, New York, 10032
About this study
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.
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).
Read the 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.
- Conditions
- Rheumatoid Arthritis
- Being tested
- TNF inhibitors, DMARDs
- Keywords
- Rheumatoid Arthritis, Cardiovascular disease, Myocardium, TNF-alpha inhibitors, ESCAPE, Co-morbidities, RHYTHM
- Medical subject headings
- Arthritis, Rheumatoid, Cardiovascular Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TNF inhibitorsDrug
Also called Anti-TNF drugs
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.
DMARDsDrug
Also called Disease-modifying antirheumatic drugs
Standard of care treatment for RA, such as Methotrexate or other disease-modifying antirheumatic drugs.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: DMARDs |
| Healthy Volunteers | No intervention | Subjects without RA who will function as controls. |
What is being measured
The primary outcome is the main question the study is designed to answer.
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."
Measured: Baseline
Secondary outcomes (3)
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."
Measured: Baseline, 6-Month Follow-up
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.
Measured: Baseline
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.
Measured: Baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Mar 2012 (estimated)
- Study start10 Oct 2011
- Primary completionSep 2019
- Study completionSep 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Rheumatoid ArthritisStudies of the same condition, open and under way.
- More trials run by Columbia UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Prevention
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 149 participants (actual)
Sponsor and investigators
- Lead sponsor
- Columbia University
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
- Responsible party
- Principal investigator, Joan M. Bathon, Columbia University
- Investigators
- Joan M Bathon, MD, Principal investigator, Columbia University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01548768
- Sponsor's protocol ID
- AAAI1026
- Other IDs
- 7R01AR050026-07
- Acronym
- RHYTHM
- Status last verified
- Nov 2020
- First submitted
- 6 Mar 2012
- Last updated
- 27 Nov 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 30407745
Study at a glance
From the registry record, last updated by the sponsor on 27 Nov 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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.
- ClinicalTrials.gov ID
- NCT01548768
- Acronym / sponsor ID
- RHYTHM / AAAI1026
- Conditions
- Rheumatoid Arthritis
- Keywords
- Rheumatoid Arthritis, Cardiovascular disease, Myocardium, TNF-alpha inhibitors, ESCAPE, Co-morbidities, RHYTHM
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 149 participants (actual)
- Lead sponsor
- Columbia UniversityUniversity, hospital or other
- Collaborators
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
- Study start
- 10 Oct 2011 (actual)
- Primary completion
- Sep 2019 (actual)
- Study completion
- Sep 2019 (actual)
- First posted
- 8 Mar 2012 (estimated)
- Results
- Posted 27 Nov 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Patients - DMARDs + TNF Inhibitors | Experimental | Drug: TNF inhibitors, Drug: DMARDsPatients 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 - DMARDs only | Active comparator | Drug: DMARDsPatients will receive their current treatment in an open label protocol in the context of standard of care. |
| Healthy Volunteers | No intervention | –Subjects without RA who will function as controls. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (18 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TNF inhibitorsAlso: Anti-TNF drugsTNF 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. | Drug | Patients - DMARDs + TNF Inhibitors |
| DMARDsAlso: Disease-modifying antirheumatic drugsStandard of care treatment for RA, such as Methotrexate or other disease-modifying antirheumatic drugs. | Drug | Patients - DMARDs + TNF Inhibitors, Patients - DMARDs only |
Primary outcome
Number of Participants With Myocardial FDG Uptake
Time frame: Baseline
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."
3 secondary outcomes
Number of Participants With Myocardial FDG Uptake After Escalation of RA Pharmacotherapy
Time frame: Baseline, 6-Month Follow-up
LV Structure (Mean EDVI) in Association With Myocardial FDG Uptake
Time frame: Baseline
LV Function (Mean Stroke Volume Index) in Association With Myocardial FDG Uptake
Time frame: Baseline
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Nov 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 30407745Amigues 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.
- Click here for information about this studyLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Joan M Bathon, MD principal investigator
Columbia University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing TNF inhibitors and DMARDs in people with Rheumatoid Arthritis, run by Columbia University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 Nov 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 27 Nov 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Myocardial FDG Uptake (time frame: Baseline). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01548768, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Nov 2020.