Ignite Creation Date:
2024-05-06 @ 12:24 AM
Last Modification Date:
2024-10-26 @ 10:49 AM
Study NCT ID:
NCT01566201
Status:
COMPLETED
Last Update Posted:
2014-12-03
First Post:
2012-03-27
Brief Title:
Effects of Interleukin-1 Inhibition on Vascular and Left Ventricular Function in Rheumatoid Arthritis Patients With Coronary Artery Disease
Sponsor:
University of Athens
Organization:
University of Athens
Study Overview
Official Title:
The Effect of Inhibition of Interleukin-1 Activity on Vascular and Left Ventricular Function in Patients With Coronary Artery Disease and Coexistent Rheumatoid Arthritis
Status:
COMPLETED
Status Verified Date:
2014-12
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Inhibition of interleukin-1 IL-1 activity in patients with RA without CAD ameliorates vascular and LV function Moreover data from species shows beneficial effect of this treatment on LV function after experimental myocardial infarction The purpose of this study is to investigate whether anakinra an IL-1 receptor antagonist improves vascular and left ventricular LV function in patients with coronary artery disease CAD and coexistent rheumatoid arthritis RA
Detailed Description:
The inflammatory processes observed in patients with rheumatoid arthritis RA are strongly linked to enhanced interleukin-1 IL-1 activity Increased IL-1 activity causes myocardial cell damage and endothelial dysfunction The adverse effects of IL-1 on myocardial and endothelial cells are mediated by an enhanced nitrooxidative stress and the promotion of apoptotic cardiomyocyte death through increased nitrooxidative stress and inflammation Anakinra a recombinant form of human IL-1 receptor antagonist is commonly used for the treatment of RA Experimental data indicates that administration of anakinra after acute myocardial infarction ameliorates cardiac remodeling by reducing cardiomyocyte apoptosis Moreover in our previous studies we have shown that treatment with anakinra reduces IL-1-mediated nitrooxidative stress and apoptotic markers leading to an improvement in Tissue Doppler and speckle tracking-derived parameters of left ventricular LV function in RA patients However it has not been defined whether inhibition of IL-1 activity by anakinra shows beneficial effects on endothelial coronary arterial and LV systolic and diastolic function in patients with coronary artery disease CAD
For this purpose we studied 60 patients with CAD and coexistent RA American Rheumatism Association criteria as well as 20 patients with RA and without CAD All the above subjects had an inadequate response to disease modifying antirheumatic drugs DMARDs and corticosteroids and were going to initiate treatment with IL-1 activity inhibitor anakinra All patients were on treatment with statins and cardioactive medications respectively for the last 6 months In the 20 patients with only RA the presence of CAD was excluded with a non-invasive test andor a negative recent coronary arteriogram
In a double-blind placebo-controlled fashion all patients were randomized to receive a single injection of anakinra100 mg sc or placebo After 48-hours patients were crossed over to the alternate treatment placebo or anakinra and measurement of the examined markers was repeated The 48h interval between the 2 consecutive studies was decided to secure a sufficient wash-out period of anakinra in accordance to the drugs half-life time
Twenty asymptomatic subjects matched for age and sex as the RA patients and with a normal ECG echocardiogram and treadmill test were selected as healthy control subjects among subjects attending the cardiology outpatients clinic
At baseline in all RA subjects and controls as well as 3-hours after the single injection of anakinra in RA subjects we assessed by means of echocardiography the following parameters a the LV dimensionsfractional shortening and wall motion score index WMSI b the systolic Sm early diastolic Em and late diastolic Am myocardial velocities of the mitral annulus by using of tissue Doppler TDI as well as the ratio of E wave of the mitral inflow measured by pulsed wave Doppler to the mean Em as an index of LV diastolic filling pressures c the LV longitudinal circumferential and radial strain and strain rate as well as Global Longitudinal strain and Torsion using speckle tracking echocardiography d the coronary flow reserve CFRafter adenosine infusion to assess coronary vasomotor function e the flow-mediated endothelial-dependent dilation of the brachial artery FMD to assess peripheral endothelial function f the diameters of aorta at systole and diastole to calculate the aortic strain as an index of local aortic properties At the same time periods we measured in blood samples a nitrotyrosine NT protein carbonyls PCand malondialdehydeMDAto assess nitrooxidative stress bsoluble Fas and Fas-ligand to assess apoptosis c interleukin-1b and tumor necrosis factor-a to assess inflammation
For this purpose we studied 60 patients with CAD and coexistent RA American Rheumatism Association criteria as well as 20 patients with RA and without CAD All the above subjects had an inadequate response to disease modifying antirheumatic drugs DMARDs and corticosteroids and were going to initiate treatment with IL-1 activity inhibitor anakinra All patients were on treatment with statins and cardioactive medications respectively for the last 6 months In the 20 patients with only RA the presence of CAD was excluded with a non-invasive test andor a negative recent coronary arteriogram
In a double-blind placebo-controlled fashion all patients were randomized to receive a single injection of anakinra100 mg sc or placebo After 48-hours patients were crossed over to the alternate treatment placebo or anakinra and measurement of the examined markers was repeated The 48h interval between the 2 consecutive studies was decided to secure a sufficient wash-out period of anakinra in accordance to the drugs half-life time
Twenty asymptomatic subjects matched for age and sex as the RA patients and with a normal ECG echocardiogram and treadmill test were selected as healthy control subjects among subjects attending the cardiology outpatients clinic
At baseline in all RA subjects and controls as well as 3-hours after the single injection of anakinra in RA subjects we assessed by means of echocardiography the following parameters a the LV dimensionsfractional shortening and wall motion score index WMSI b the systolic Sm early diastolic Em and late diastolic Am myocardial velocities of the mitral annulus by using of tissue Doppler TDI as well as the ratio of E wave of the mitral inflow measured by pulsed wave Doppler to the mean Em as an index of LV diastolic filling pressures c the LV longitudinal circumferential and radial strain and strain rate as well as Global Longitudinal strain and Torsion using speckle tracking echocardiography d the coronary flow reserve CFRafter adenosine infusion to assess coronary vasomotor function e the flow-mediated endothelial-dependent dilation of the brachial artery FMD to assess peripheral endothelial function f the diameters of aorta at systole and diastole to calculate the aortic strain as an index of local aortic properties At the same time periods we measured in blood samples a nitrotyrosine NT protein carbonyls PCand malondialdehydeMDAto assess nitrooxidative stress bsoluble Fas and Fas-ligand to assess apoptosis c interleukin-1b and tumor necrosis factor-a to assess inflammation
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None