Methotrexate, Blood Pressure and Arterial Function in Rheumatoid Arthritis

Phase

Condition

Musculoskeletal Diseases

Bone Diseases

Rheumatoid Arthritis

Treatment

Methotrexate

Sulfasalazine

Other DMARDs

Clinical Study ID

NCT03254589

HREC/17/SAC/46

Ages > 18
All Genders

Study Summary

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

Eligibility Criteria

Inclusion

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-relatedprocedure.

Exclusion

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 useof three antihypertensive agents of different classes, one of which is a diuretic.
Clinical systolic blood pressure <100 mm Hg or history of symptomatic orthostatichypotension.
Cardiovascular event, procedure, or hospitalization for unstable angina with thelast 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 theopinion of the study staff, the participant is cognitively unable to follow theprotocol.
Other medical, psychiatric, or behavioural factors that in the judgment of the studystaff may interfere with study participation.
Cancer diagnosed and treated within the past 2 years that, in the judgment of thestudy staff, would compromise a participant's ability to comply with the protocoland complete the study.
Any organ transplant.
Pregnancy, currently trying to become pregnant, or of child bearing potential andnot using birth control.
Significant illness within 2 weeks of study start.
Patients with an unstable active medical condition that could impair evaluation ofstudy results.

Study Design

Methotrexate

October 01, 2017

December 31, 2023

Study 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.

Connect with a study center

Southern Adelaide Local Health Network
Bedford Park, South Australia 5042
Australia
Site Not Available

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