Methotrexate, Blood Pressure and Arterial Function in Rheumatoid Arthritis

Rheumatoid Arthritis Clinical Trial

Official title:

Methotrexate, Blood Pressure and Arterial Function in Rheumatoid Arthritis

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03254589
• Other study ID #: HREC/17/SAC/46
• Status: Recruiting
• Phase: Phase 4
• Start date: October 1, 2017
• Est. completion date: December 31, 2024

Study information

• Verified date: July 2022
• Source: Flinders University
• Contact: Arduino A Mangoni, MD, PhD
• Phone: 0061882047495
• Email: arduino.mangoni[@]flinders.edu.au
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The investigators will study the effects of methotrexate on blood pressure, arterial stiffness and endothelial function in patients with rheumatoid arthritis.

Description:

Patients with rheumatoid arthritis have an increased risk of stroke and heart attack when compared to the rest of the population. Recent studies have shown that methotrexate, a disease-modifying antirheumatic drug (DMARDs) commonly prescribed for rheumatoid arthritis, reduces this risk. However, the mechanisms responsible for the protective effects of methotrexate on the heart and the brain are unknown. The investigators have recently completed an observational study in participants with rheumatoid arthritis treated with either methotrexate or with other DMARDs. Participants on methotrexate had lower blood pressure and 'healthier' blood vessels than participants treated with other DMARDs. These differences were maintained over a period of 8 months. These results suggest that methotrexate lowers blood pressure and exerts salutary effects on blood vessels, which might explain the reduced risk of stroke and heart attack with this drug. However, the observational nature of this study does not allow establishing a clear cause-effect relationship between methotrexate treatment and the observed changes in blood pressure and blood vessels. In order to address this issue, the investigators will recruit participants that have been recently diagnosed with rheumatoid arthritis and are about to start treatment with either methotrexate (Group 1) or another DMARD (Group 2). Then, the investigators will assess their blood pressure and blood vessels for 6 months. The investigators will use an injectable (subcutaneous) form of methotrexate because this might provide better effects on blood pressure and blood vessels. The investigators will also study a third group (Group 3) of rheumatoid arthritis participants already on treatment (> 1 year) with oral methotrexate, with or without other DMARDs. They will be switched to subcutaneous methotrexate, but continuing all their other medications, for 6 months to see whether the subcutaneous form can further reduce blood pressure and provide additional salutary effects on blood vessels. Finally, the investigators will study a fourth group (Group 4) of participants with rheumatoid arthritis already on treatment (> 1 year) with DMADRs other than methotrexate who will continue with the same medications for 6 months, to assess possible fluctuations in blood pressure and blood vessel markers over time. Each participant will attend three study visits (baseline, 1 and 6 months), each lasting between 60 and 90 min.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 124
• Est. completion date: December 31, 2024
• Est. primary completion date: December 31, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patient with rheumatoid arthritis according to EULAR/ACR 2010 criteria.
• Age =18 years.
• Written informed consent, dated and signed before initiating any study-related procedure.

Exclusion Criteria:

• Contraindication to MTX or sulfasalazine.
• Patient who cannot be followed during 6 months.
• Active alcohol or substance abuse within the last 12 months.
• Participation in a clinical trial within 3 months prior to the start of the study.
• Body mass index >35 Kg/m2.
• Secondary causes of hypertension.
• Grade 2 (moderate) or 3 (severe) hypertension: clinic blood pressure >160/100 mm Hg.
• Resistant hypertension: clinical blood pressure =140/90 mm Hg despite concurrent use of three antihypertensive agents of different classes, one of which is a diuretic.
• Clinical systolic blood pressure <100 mm Hg or history of symptomatic orthostatic hypotension.
• Cardiovascular event, procedure, or hospitalization for unstable angina with the last 6 months.
• Atrial fibrillation.
• Heart failure.
• Treatment with nitrates.
• Estimated glomerular filtration rate (eGFR) <45 mL/min.
• Diagnosis of polycystic kidney disease.
• Glomerulonephritis treated with or likely to be treated with immunosuppressant drugs
• Uncontrolled diabetes with HbA1c >9.0% (>75 mmol/mol).
• Uncontrolled dyslipidaemia with total serum cholesterol >7.5 mmol/L or triglycerides >5.6 mmol/L.
• Clinical diagnosis of dementia, treatment with medications for dementia or, in the opinion of the study staff, the participant is cognitively unable to follow the protocol.
• Other medical, psychiatric, or behavioural factors that in the judgment of the study staff may interfere with study participation.
• Cancer diagnosed and treated within the past 2 years that, in the judgment of the study staff, would compromise a participant's ability to comply with the protocol and complete the study.
• Any organ transplant.
• Pregnancy, currently trying to become pregnant, or of child bearing potential and not using birth control.
• Significant illness within 2 weeks of study start.
• Patients with an unstable active medical condition that could impair evaluation of study results.

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Cardiovascular Risk Factor
• Endothelial Dysfunction
• Rheumatoid Arthritis
• Stiffness, Aortic

Intervention

Drug:
• Methotrexate
See arm descriptions
• Sulfasalazine
See arm description
• Other DMARDs
See arm

Locations

Country	Name	City	State
Australia	Southern Adelaide Local Health Network	Bedford Park	South Australia

Sponsors (3)

Lead Sponsor	Collaborator
Flinders University	medac GmbH, University of South Australia

Country where clinical trial is conducted

Australia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in peripheral systolic blood pressure	Change in peripheral systolic blood pressure	Change from baseline peripheral systolic blood pressure at 6 months
Secondary	Change in peripheral and central blood pressure	Change in peripheral and central blood pressure	Change from baseline peripheral and central blood pressure at 6 months
Secondary	Change in arterial stiffness	Change in pulse wave velocity	Change from baseline pulse wave velocity at 6 months
Secondary	Change in arterial wave reflection	Change in augmentation index	Change from baseline augmentation index at 6 months
Secondary	Change in adenosine	Change in adenosine concentrations	Change from baseline adenosine concentrations at 6 months
Secondary	Change in arginine metabolites	Change in ADMA concentrations	Change from baseline ADMA concentrations at 6 months