Devlopment of Heart and blood vessel problems in patients with conditions which cause long-term, widespread, inflammation in the body.

Phase 1

• Conditions: Rheumatoid Arthritis; MedDRA version: 14.1 Level: HLT Classification code 10039075 Term: Rheumatoid arthritis and associated conditions System Organ Class: 100000004870; Therapeutic area: Diseases [C] - Immune System Diseases [C20]

• Registration Number: EUCTR2007-005464-26-GB
• Lead Sponsor: Kings College London

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2008-04-11
• Study Completion: 2014-04-30
• Last Update Posted: 25 November 2019

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Not specified
• Target Recruitment: 14

Inclusion Criteria

1. Male and female subjects over 18 years of age
2. Systemic inflammatory conditions (rheumatoid arthritis) diagnosis established independently by the clinical team
3. Eligiblilty for anti-TNF-alpha therapy- decision to start treatment reached independently by the clinical team.
4.Woman of childbearing potential must have a negative serum pregnancy test within 7 days of the first adminstration of study treatment, and must be willing to use a reliable form of contraception to prevent pregnancy.
5. Provision of signed, informed, consent.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 100
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 100

Exclusion Criteria

1. Inability to tolerate scanning (claustrophobia, inability to lie flat);
2. Contra-indications to MRI (implantable devices, hypersensitivity to Gadolinium-
containing contrast agents, weight over 120kg);
3. Inability to give informed consent;
4. Non-sinus rhythm;
5. Above 70 years of age.
6. Diagnosis of tuberculosis or other severe infections such as sepsis, abscesses, and opportunistic infections, chronic infection or a history of recurrent infection.
7. Moderate or severe heart failure (NYHA class III/IV)
8. Patients with a history of hypersensitivity to infliximab, entanercept, adalimumab or other murine proteins, or to any of the excipients
9. Concomitant use of immunosuppressive therapy, anakinra, abatacept, sulfasalazine
or live vaccinations
10. Patient with a history of Hepatitis B and C virus infection
11.Patients with a history of malignancy
12.Significantly impaired renal function (eGFR >60 ml/min/1.73m2)
13.Significantly impaired hepatic function (alkaline transaminase twice above the upper limit of the normal range)
14.Pre-existing blood dyscrasias, such as significant marrow hypoplasia, leukopenia,
thrombocytopenia or anaemia
15. Current pregnancy or lactation.
16. Patients with any significant history of non-compliance to medical regimens.
17. History of asthma, significant bradycardia and arrhythmias
18. Known hypersensitivity to adenosine
19. Known or suspected bronchostrictive or bronchospasti disease
20. Second- or third- degree atrioventricular (AV) block, sinus bradychardia (heart rate <45 bpm)
21. Systemic arterial hypotension (<90mm Hg)

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To investigate TNF-alpha inhibitors altering cardiovascular function in patients with systemic inflammatory conditions (FMD, LV mass/LV volumes);Secondary Objective: Atherosclerotic plaque burden, Vascular distensibility and stiffness, Global and regional, systolic and diasystolic function and tissue characterisation, haematological and biochemical indices of vascular inflammation, myocardial microvascular function;<br> Primary end point(s): Primary Outcomes:<br> 1. Aortic distensiblity and stiffness studies (PWV and AD)<br> 2.Myocardial function (LV mass, LV volumes)<br> ;Timepoint(s) of evaluation of this end point: Prior to starting anti-TNF therapy and 3, 6, 18, months afterwards

Secondary Outcome Measures

Name	Time	Method
<br> Secondary end point(s): Secondary outcomes:<br> 1.Atherosclerotic plaque burden<br> 2.Global and regional, systolic and diastolic function and tissue characterisation <br> 3.Myocardial microvascular function (coronary flow reserve)<br> ;Timepoint(s) of evaluation of this end point: Prior to starting anti-TMF therapy and 3, 6, 18, months afterwards