Enalapril Maleate on Arterial Stiffness in Rheumatoid Arthritis.

Rheumatoid Arthritis Clinical Trial

Official title:

Effect of Prophylactic Treatment With Enalapril Maleate on Arterial Stiffness in Rheumatoid Arthritis Patients.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03667131
• Other study ID #: EEVA
• Status: Completed
• Phase: Phase 2
• Start date: February 13, 2017
• Est. completion date: February 19, 2018

Study information

• Verified date: November 2018
• Source: University of Guadalajara
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study evaluates the effect in artery stiffness of enalapril maleate in Rheumatoid Arthritis women patients. Half of participants will receive 5 mg enalapril maleate every 12 hrs, while the other half will receive a placebo.

Description:

Rheumatoid Arthritis (RA) is a chronic inflammatory systemic disease considered as an independent cardiovascular risk factor that is associated with cumulative inflammatory load with an elevation of circulating levels of cytokines, which mediate the mechanism of endothelial cells activation by increasing the angiotensin converting enzyme (ACE) function and generation of vasoconstriction. Enalapril maleate is a prodrug that is hydrolyzed by hepatic esterases in enalaprilat, which is a potent inhibitor of ACE. ACE inhibition decreases vascular systemic resistance and mean, diastolic and systolic blood pressures in several hypertensive states, independently of the mechanism, ACE inhibitors have a widespread clinic use for cardiovascular diseases. Therefore, the researchers considered that there could be an association between the use of enalapril and the decrease in arterial stiffness.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 59
• Est. completion date: February 19, 2018
• Est. primary completion date: December 8, 2017
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• Patients classified with RA according to the American College of Rheumatology (ACR) / European League Against Rheumatism (EULAR) 2010

• Patients treated in the outpatient service of the Rheumatology Service of the Hospital Civil de Guadalajara "Dr. Juan I Menchaca".

• Sign an Informed Consent Letter

• Under treatment with conventional Disease-Modifying Antirheumatic Drugs (DMARDS)

Exclusion Criteria:

• Patients with a previous diagnosis of diabetes mellitus, systemic hypertension, thyroid, kidney or liver disease

• History of acute myocardial infarction, cardiac arrhythmias, cerebral vascular event or heart failure

• Smoking active patients in the last 6 months

• Patients with a desire for close conception, pregnant or breastfeeding.

• Patients with blood pressure <90/60 mmHg

• Patients who do not accept to participate in the study

• Patients with a BMI greater than =40 Kg / m2

• Non-palpable carotid and femoral pulses

• Unstable psychological state

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Rheumatoid Arthritis

Intervention

Drug:
• Enalapril Maleate
Enalapril Maleate 5 mg tablet, every 12 hrs for 90 days.
• Placebo
Placebo 5 mg tablet, every 12 hrs for 90 days.

Locations

Country	Name	City	State
Mexico	Instituto de Investigación en Reumatología y Sistema Músculo Esquelético	Guadalajara	Jalisco

Sponsors (1)

Lead Sponsor	Collaborator
University of Guadalajara

Country where clinical trial is conducted

Mexico, 

References & Publications (15)

Burmester GR, Feist E, Dörner T. Emerging cell and cytokine targets in rheumatoid arthritis. Nat Rev Rheumatol. 2014 Feb;10(2):77-88. doi: 10.1038/nrrheum.2013.168. Epub 2013 Nov 12. Review. — View Citation

Crilly MA, Kumar V, Clark HJ, Scott NW, Macdonald AG, Williams DJ. Arterial stiffness and cumulative inflammatory burden in rheumatoid arthritis: a dose-response relationship independent of established cardiovascular risk factors. Rheumatology (Oxford). 2009 Dec;48(12):1606-12. doi: 10.1093/rheumatology/kep305. Epub 2009 Oct 25. — View Citation

Crowson CS, Nicola PJ, Kremers HM, O'Fallon WM, Therneau TM, Jacobsen SJ, Roger VL, Ballman KV, Gabriel SE. How much of the increased incidence of heart failure in rheumatoid arthritis is attributable to traditional cardiovascular risk factors and ischemic heart disease? Arthritis Rheum. 2005 Oct;52(10):3039-44. — View Citation

Gibofsky A. Overview of epidemiology, pathophysiology, and diagnosis of rheumatoid arthritis. Am J Manag Care. 2012 Dec;18(13 Suppl):S295-302. — View Citation

Gkaliagkousi E, Gavriilaki E, Doumas M, Petidis K, Aslanidis S, Stella D. Cardiovascular risk in rheumatoid arthritis: pathogenesis, diagnosis, and management. J Clin Rheumatol. 2012 Dec;18(8):422-30. doi: 10.1097/RHU.0b013e31827846b1. Review. — View Citation

Gossec L, Dougados M, Dixon W. Patient-reported outcomes as end points in clinical trials in rheumatoid arthritis. RMD Open. 2015 Apr 2;1(1):e000019. doi: 10.1136/rmdopen-2014-000019. eCollection 2015. Review. — View Citation

Klocke R, Cockcroft JR, Taylor GJ, Hall IR, Blake DR. Arterial stiffness and central blood pressure, as determined by pulse wave analysis, in rheumatoid arthritis. Ann Rheum Dis. 2003 May;62(5):414-8. — View Citation

Kramer HR, Giles JT. Cardiovascular disease risk in rheumatoid arthritis: progress, debate, and opportunity. Arthritis Care Res (Hoboken). 2011 Apr;63(4):484-99. doi: 10.1002/acr.20386. Review. — View Citation

Kremers HM, Crowson CS, Therneau TM, Roger VL, Gabriel SE. High ten-year risk of cardiovascular disease in newly diagnosed rheumatoid arthritis patients: a population-based cohort study. Arthritis Rheum. 2008 Aug;58(8):2268-74. doi: 10.1002/art.23650. — View Citation

Park S, Lakatta EG. Role of inflammation in the pathogenesis of arterial stiffness. Yonsei Med J. 2012 Mar;53(2):258-61. doi: 10.3349/ymj.2012.53.2.258. Review. — View Citation

Roman MJ, Devereux RB, Schwartz JE, Lockshin MD, Paget SA, Davis A, Crow MK, Sammaritano L, Levine DM, Shankar BA, Moeller E, Salmon JE. Arterial stiffness in chronic inflammatory diseases. Hypertension. 2005 Jul;46(1):194-9. Epub 2005 May 23. — View Citation

Solomon DH, Karlson EW, Rimm EB, Cannuscio CC, Mandl LA, Manson JE, Stampfer MJ, Curhan GC. Cardiovascular morbidity and mortality in women diagnosed with rheumatoid arthritis. Circulation. 2003 Mar 11;107(9):1303-7. — View Citation

Vázquez-Del Mercado M, Gomez-Bañuelos E, Chavarria-Avila E, Cardona-Muñoz E, Ramos-Becerra C, Alanis-Sanchez A, Cardona-Muller D, Grover-Paez F, Perez-Vazquez FJ, Navarro-Hernandez RE, Valadez-Soto JM, Saldaña-Millan AA, Gonzalez-Rosas L, Ramos-Lopez G, Petri MH, Bäck M. Disease duration of rheumatoid arthritis is a predictor of vascular stiffness: a cross-sectional study in patients without known cardiovascular comorbidities: A STROBE-compliant article. Medicine (Baltimore). 2017 Aug;96(33):e7862. doi: 10.1097/MD.0000000000007862. — View Citation

Vázquez-Del Mercado M, Nuñez-Atahualpa L, Figueroa-Sánchez M, Gómez-Bañuelos E, Rocha-Muñoz AD, Martín-Márquez BT, Corona-Sanchez EG, Martínez-García EA, Macias-Reyes H, Gonzalez-Lopez L, Gamez-Nava JI, Navarro-Hernandez RE, Nuñez-Atahualpa MA, Andrade-Garduño J. Serum levels of anticyclic citrullinated peptide antibodies, interleukin-6, tumor necrosis factor-a, and C-reactive protein are associated with increased carotid intima-media thickness: a cross-sectional analysis of a cohort of rheumatoid arthritis patients without cardiovascular risk factors. Biomed Res Int. 2015;2015:342649. doi: 10.1155/2015/342649. Epub 2015 Mar 2. — View Citation

Wållberg-Jonsson S, Caidahl K, Klintland N, Nyberg G, Rantapää-Dahlqvist S. Increased arterial stiffness and indication of endothelial dysfunction in long-standing rheumatoid arthritis. Scand J Rheumatol. 2008 Jan-Feb;37(1):1-5. doi: 10.1080/03009740701633238. — View Citation

* Note: There are 15 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Pulse Wave Velocity (PWV)	This is a measure of arterial stiffness, or the rate at which pressure waves move down the vessel.	Baseline and 90 days
Secondary	Change in Cardio-Ankle Vascular Index	This is calculated from PWV at the origin of the aorta to the ankle portion of the tibial artery, and systolic and diastolic blood pressures measured at the upper brachial artery.	Baseline and 90 days