Clinical trial NCT00273533: Ramipril in Rheumatoid Arthritis
Official title: Effects of Ramipril on Endothelial Function in Patients With Rheumatoid Arthritis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Arthritis, Rheumatoid
Lead sponsor: University of Zurich
Sponsor class: OTHER
Collaborators: name: Sanofi
First posted: 2006-01-09
Enrollment: 13
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: The present study is designed to evaluate the hypothesis that the Angiotensin-Converting Enzyme (ACE) inhibitor Ramipril improves vascular function and reduces markers of low-grade chronic inflammation and oxidative stress in patients with Rheumatoid Arthritis.

Detailed description: The effect of an 8-week treatment with either ramipril or placebo is studied using a randomized, double-blind, and crossover protocol. After given written informed consent, baseline characteristics including physical examination, ECG, blood sample and a noninvasive assessment of endothelial function are obtained. The patients are randomly assigned to receive either ramipril 10mg (up-titration-scheme: starting with 2.5mg in Week1, then 5mg in Week2 followed by 2-5mg for the final 6 weeks) followed by placebo or vice versa.The individual disease-modifying antirheumatic drug therapy is continued throughout the study. The examinations are repeated after 8 weeks treatment of the first and 8 weeks after the second study drug. At week 1 and 2 in each treatment period a safety visit is scheduled.

Eligibility criteria: Inclusion Criteria:

* patients with rheumatoid arthritis (4 out of 7 ARA criteria must be fulfilled to establish diagnosis) on stable background therapy for the last three months
* endothelial dysfunction (FMD \< 4%, FMD:Flow-Mediated-Dilatation)
* non-smokers

Exclusion Criteria:

* previous myocardial infarction, coronary intervention or coronary surgery
* previous treatment with statins in the last 6 months
* previous treatment with ACE-inhibitors in the last 6 months
* uncontrolled hypertension SAP/DAP \> 160/90 mmHg (SAP:Systolic Arterial Pressure, DAP:Diastolic Arterial Pressure)
* dyslipidemia (LDL-cholesterol \> 4.9 mmol)
* normal CRP \< 3 mg/l
* overweight BMI \> 35kg/m2
* anaemia (hemoglobin \< 10g/dl)
* kidney disease (creatinine \> 150 umol/l)
* insulin-dependent diabetes mellitus
* congestive heart failure (\> NYHA I)
* AV-Block\>I
* pregnancy
* angio-edema
* malignancy or chronic infection
* drug abuse

Primary outcomes:
measure: Endothelial dysfunction evaluated on weeks 8 and 16.
Secondary outcomes:
measure: Alteration of inflammatory parameters: C-reactive Protein, TNFa, Interleukin 6 on weeks 8 and 16.
Other outcomes:
Locations:
Study officials:
affiliation: Sanofi
name: Ali Shokry
role: STUDY_DIRECTOR
References:
citation: Flammer AJ, Sudano I, Hermann F, Gay S, Forster A, Neidhart M, Kunzler P, Enseleit F, Periat D, Hermann M, Nussberger J, Luscher TF, Corti R, Noll G, Ruschitzka F. Angiotensin-converting enzyme inhibition improves vascular function in rheumatoid arthritis. Circulation. 2008 Apr 29;117(17):2262-9. doi: 10.1161/CIRCULATIONAHA.107.734384. Epub 2008 Apr 21.