Enalapril Maleate on Arterial Stiffness in Rheumatoid Arthritis.

NCT03667131 | Completed Phase 2 DMC

• 1 other identifier: EEVA
• Study Type: interventional
• Target: 59
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Rheumatoid Arthritis

Keywords

arterial stiffness; enalapril maleate

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• Change in Cardio-Ankle Vascular Index

  Baseline and 90 days

Study Arms (2)

Enalapril Maleate

EXPERIMENTAL

Enalapril Maleate 5 mg every 12 hrs for 90 days.

Drug: Enalapril Maleate

Placebo

EXPERIMENTAL

Substance that lacks in itself therapeutic action.

Drug: Placebo

Interventions

Enalapril Maleate DRUG

Enalapril Maleate 5 mg tablet, every 12 hrs for 90 days.

Also known as: Angiotensin converting enzyme inhibitor.

Enalapril Maleate

Placebo DRUG

Placebo 5 mg tablet, every 12 hrs for 90 days.

Also known as: Inactive drug

Placebo

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Guadalajara: lead

Study Sites (1)

Instituto de Investigación en Reumatología y Sistema Músculo Esquelético

Guadalajara, Jalisco, 44340, Mexico

Location

Related Publications (16)

• 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.

  PMID: 26509052 BACKGROUND

• Burmester GR, Feist E, Dorner 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.

  PMID: 24217582 BACKGROUND

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

  PMID: 23327517 BACKGROUND

• 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.

  PMID: 23188207 BACKGROUND

• 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. doi: 10.1161/01.cir.0000054612.26458.b2.

  PMID: 12628952 BACKGROUND

• 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. No abstract available.

  PMID: 21452262 BACKGROUND

• 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. doi: 10.1002/art.21349.

  PMID: 16200583 BACKGROUND

• 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.

  PMID: 18668561 BACKGROUND

• 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.

  PMID: 19858120 BACKGROUND

• 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. doi: 10.1136/ard.62.5.414.

  PMID: 12695151 BACKGROUND

• 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.

  PMID: 22318811 BACKGROUND

• 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. doi: 10.1161/01.HYP.0000168055.89955.db. Epub 2005 May 23.

  PMID: 15911740 BACKGROUND

• Vazquez-Del Mercado M, Nunez-Atahualpa L, Figueroa-Sanchez M, Gomez-Banuelos E, Rocha-Munoz AD, Martin-Marquez BT, Corona-Sanchez EG, Martinez-Garcia EA, Macias-Reyes H, Gonzalez-Lopez L, Gamez-Nava JI, Navarro-Hernandez RE, Nunez-Atahualpa MA, Andrade-Garduno J. Serum levels of anticyclic citrullinated peptide antibodies, interleukin-6, tumor necrosis factor-alpha, 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.

  PMID: 25821796 BACKGROUND

• Wallberg-Jonsson S, Caidahl K, Klintland N, Nyberg G, Rantapaa-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.

  PMID: 18189187 BACKGROUND

• Vazquez-Del Mercado M, Gomez-Banuelos E, Chavarria-Avila E, Cardona-Munoz E, Ramos-Becerra C, Alanis-Sanchez A, Cardona-Muller D, Grover-Paez F, Perez-Vazquez FJ, Navarro-Hernandez RE, Valadez-Soto JM, Saldana-Millan AA, Gonzalez-Rosas L, Ramos-Lopez G, Petri MH, Back 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.

  PMID: 28816989 BACKGROUND

• Perez-Vazquez F, Back M, Chavarria-Avila E, Gomez-Banuelos E, Ramos-Becerra CG, Pizano-Martinez O, Salazar-Paramo M, Grover-Paez F, Nava-Zavala AH, Cardona-Munoz EG, Cardona-Muller D, Duran-Barragan S, Mera-Riofrio VN, Prado-Bachega N, Vazquez-Del Mercado M. Enalapril Influence on Arterial Stiffness in Rheumatoid Arthritis Women: A Randomized Clinical Trial. Front Med (Lausanne). 2020 Jan 29;6:341. doi: 10.3389/fmed.2019.00341. eCollection 2019.

  PMID: 32118001 DERIVED

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

Enalapril; Angiotensin-Converting Enzyme Inhibitors

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Dipeptides; Oligopeptides; Peptides; Amino Acids, Peptides, and Proteins; Protease Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses

Study Officials

• Monica Vázquez-Del Mercado, MD, PhD

  University of Guadalajara

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Participant, care provider, investigator and outcomes assessor.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: PhD

Model Details: Randomized, double blind, controlled, parallel groups clinical trial.

Study Record Dates

• First Submitted: September 10, 2018
• First Posted: September 12, 2018
• Study Start: February 13, 2017
• Primary Completion: December 8, 2017
• Study Completion: February 19, 2018
• Last Updated: November 14, 2018

Record last verified: 2018-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF, CSR
• Time Frame: Data will be available within one year of study completion.
• Access Criteria: Data access requests will be reviewed by an external independent Review Panel. Requests will be required to sign a Data Access Agreement.

Locations

ME (1)