Clinical Study Evaluating the Effect of Carvedilol in Patients With Active Rheumatoid Arthritis
试验速览
- 阶段
- 早期 1 期
- 状态
- 尚未招募
- 入组人数
- 70
- 主要终点
- change in DAS-28-CRP score and the Multidimensional Health Assessment Questionnaire (MDHAQ) scores.
研究概览
简要总结
This study aims at investigating the possible efficacy and safety of carvedilol as an adjunctive therapy in patients with active rheumatoid arthritis and hypertension.
详细描述
heumatoid arthritis (RA) is a chronic systemic autoimmune disease that primarily affects the lining of the synovial joints and is associated with progressive disability, premature death, and socioeconomic burdens. It is characterized with chronic production of pro-inflammatory cytokines, which lead to cartilage and bone degradation that results in tissue destruction by the patients' immune system (Guo et al., 2018).
The high systemic inflammatory burden associated with RA appears to be a key driver of increased CV risk. This inflammatory state is linked to endothelial dysfunction and accelerated atherosclerosis (Giollo et al., 2018). Consequently, RA increases the risk of cardiovascular (CV) mortality by up to 50% compared with the general population and CV disease is the leading cause of death in RA patients. This leads to suggestion that reducing inflammation lowers CV risk in RA (Dijkshoorn et al., 2022).
Therapies targeting inflammation remain the mainstay of RA treatment such as non- steroidal anti-inflammatory drugs (NSAIDs), non-biologic and biologic disease-modifying anti-rheumatic drugs (DMARDs), immune-osuppressants, and corticosteroids. However, current treatment strategies have many adverse effects and a significant proportion of RA patients did not effectively respond to them (Aletaha and Smolen., 2018). Consequently, it is crucial to find new therapeutic approaches for the management of inflammation as well as the prevention of cardiovascular complications in rheumatoid arthritis patients.
Carvedilol is a non-selective β-blocker with α-adrenergic receptor antagonism properties which has been safely used in treatment of several cardiovascular disorders (Prajapati et al., 2017). Previous animal studies highlights evidences for the promising anti- arthritic effects of carvedilol that could be mediated through attenuation of leukocyte migration, alleviation of oxidative stress and suppression of pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interlukin-6 (IL-6) and eicosanoids including prostaglandin E2 (PGE2) and leukotriene B4 (LTB4) (Arab and El-Sawalhi, 2013; Ahmed et al., 2017; Osman et al., 2017).
Taken together, carvedilol has powerful antioxidant/anti-inflammatory properties; we aimed to investigate its protective potential against arthritis that may add further benefits for its clinical usefulness especially in RA patients with concomitant cardiovascular disorders
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 盲法
- Double (Participant, Investigator)
盲法说明
The blindness will be maintained by the similarity between the placebo and carvedilol tablets. The patients will be randomized by a neutral researcher using sealed envelope method with assigned code into two groups
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with active rheumatoid arthritis (not in remission) according to American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) 2010 criteria i.e 28 joints disease activity score (DAS-28) >2.
- •Patients with hypertension who are candidate to carvidolol.
- •Age range between 18 and 60 years old.
- •The studywillbecarriedoutbetween June 2023 and June
- •Both sexes.
- •Sex ratio, body mass index (BMI), age, disease activity, and disease duration matched patients.
- •Patients receive matched doses of standard treatment including methotrexate, non-steroidal anti-inflammatory drugs, selective cyclooxygenase-2 inhibitors, acetaminophen, and low dose of oral corticosteroids (prednisolone < 15 mg) will be allowed to be enrolled the trial.
- •Intravenous, intra-articular or intramuscular corticosteroids; intra-articular hyaluronate sodium and biological DMARDs will not be permitted less than 4 weeks before the first dose of carvedilol.
排除标准
- •Patients with congestive heart failure, other heart disease (arrhythmia, ischemic heart disease including angina and myocardial infarction).
- •Patients with other inflammatory diseases and active infection.
- •Patients with glaucoma.
- •Patients with asthma, COPD, other lung diseases.
- •Patients with hepatic and biliary diseases.
- •Patients with chronic renal failure or those on dialysis.
- •Patients with peripheral intermittent claudication and peripheral circulatory disorders.
- •Patients receiving oral pednisolone greater than 15 mg/day.
- •Patients receiving biological DMARDs.
- •Patients with hypersensitivity to carvedilol.
- •Patients using antioxidants.
- •Pregnant and lactating females.
- •Patients receiving digitalis, anti-arrhythmic (amiodarone, propafenone) MAOI, cyclosporine, calcium channel blockers (verapamil, deltiazem), beta blockers, other antihypertensive medications hepatic microsomal enzymes inducers or inhibitors (phenytoin, rifampin, valoproate), oral hypoglycemic and insulin to avoid potential pharmacodynamics
研究组 & 干预措施
Control group
Group1 (Placebo group; n=35) which will receive the standard treatment for RA plus placebo tablet for 3 months.
干预措施: Carvedilol (Drug)
Treatment group
Group 2 (Carvedilol group; n=35) which will receive the standard treatment for RA plus carvedilol 12.5mg once a day for 2 days; this is increased to 25 mg once a day or 12.5 mg twice a day for 3 months.
干预措施: Carvedilol (Drug)
结局指标
主要结局
change in DAS-28-CRP score and the Multidimensional Health Assessment Questionnaire (MDHAQ) scores.
时间窗: 12 week
By the end of the study we should notice decrease in DAS-28-CRP score and the Multidimensional Health Assessment Questionnaire (MDHAQ) scores.
次要结局
- change in the serum level of the assessed biological markers(12 week)
研究者
Yomna Abdelrafea Ahmed
Investigator
Tanta University