The GRK2 Inhibitor Paroxetine as a Novel Adjunct to Conventional Therapy in Rheumatoid Arthritis Patients. A Proof-of-Concept, Randomized, Double-Blind, Placebo-Controlled Trial.
试验速览
- 阶段
- 1 期
- 状态
- 撤回
- 发起方
- 入组人数
- 100
- 试验地点
- 1
- 主要终点
- ACR50 & ACR70 response rate
研究概览
简要总结
Among three MAPK families, paroxetine was found to be able to decrease the phosphorylation of ERK. It was reported that paroxetine attenuates the symptoms of collage induced arthritis rats due to its inhibitory effect on T cell activation and infiltration to synovial tissue via suppression of ERK pathway. This study aimed to evaluate the therapeutic efficacy of paroxetine in rheumatoid arthritis. Paroxetine prevents the joint inflammation which is at the very early stage. paroxetine could inhibit GRK2 with selectivity over other GRKs. Medications developed for maintaining the immunologic equilibrium. such as GRK2 inhibitors, will be the novel trends in RA treatment that could avoid the adverse side effects that are common with current treatment options.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
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 based on DAS28 score. Patients received the standard therapy (i.e. one or more conventional DMARDs) for at least three months.
排除标准
- •Known hypersensitivity to metformin.
- •Patients who have a prior diagnosis with diabetes mellitus.
- •Patients receive metformin for any other indications.
- •Patients with congestive heart failure.
- •Patients with a history of myocardial infarction.
- •Patients with severe anemia.
- •Patients with active infections or other inflammatory diseases.
- •Patients receiving biological therapy.
- •Pregnancy or lactation.
- •Patients with impaired liver functions.
- •Patients with impaired kidney functions (serum creatinine concentrations ≥1.5 and ≥1.4 mg/dL in males and females respectively).
- •Patients with malignancies.
研究组 & 干预措施
Paroxetine
Paroxetine 20 mg daily plus standard therapy
干预措施: Paroxetine (Drug)
Placebo
Placebo tablet daily plus standard therapy
干预措施: Placebo (Drug)
结局指标
主要结局
ACR50 & ACR70 response rate
时间窗: week 12
based on tender and swollen joint counts, patient's assessment of pain, patient and physician global assessment of arthritis, Health Assessment Questionnaire Disability Index (HAQ DI), and CRP level
ACR 20% improvement criteria (ACR20) response rate
时间窗: week 12
based on tender and swollen joint counts, patient's assessment of pain, patient and physician global assessment of arthritis, Health Assessment Questionnaire Disability Index (HAQ DI), and CRP level
Disease activity scale in 28 joints (DAS-28)
时间窗: week 12
Scale assessing severity of rheumatoid arthritis based on number of tender, swollen joints, erythrocyte sedimentation rate (ESR) levels, and patient self-assessment of his condition (global health assessment). Whereas "28" describes the number of different joints including in the measurement: proximal interphalangeal joints (10 joints), metacarpophalangeal joints (10), wrists (2), elbows (2), shoulders (2), knees (2).
次要结局
- GRK2 expression(week 12)
- Inteleukins(12 weeks)
- Drug Adverse effects(12 weeks)
- CRP(12 weeks)
- TNF-α(week 12)
研究者
Mahmoud Samy Abdallah
Lecturer of Clinical Pharmacy
Sadat City University