Clinical Study Evaluating the Possible Efficacy and Protective Effect of Empagliflozin in Rheumatoid Arthritis Patients Treated with Methotrexate
试验速览
- 阶段
- 4 期
- 状态
- 尚未招募
- 入组人数
- 44
- 试验地点
- 1
- 主要终点
- calculation of DAS28-CRP score for measure disease activity
研究概览
简要总结
The primary aim of this clinical trial is to Evaluate the Possible Efficacy and Protective Effect of Empagliflozin in Rheumatoid Arthritis Patients Treated with Methotrexate.
Methodology:
This is a randomized, double blind placebo controlled parallel study that will be conducted on 44 patients with active rheumatoid arthritis.
Group1 (placebo group; n=22) which will receive IM or SC Methotrexate plus placebo tablet once daily for 3 months.
Group2 (Empa group; n=22) which will receive IM or SC Methotrexate plus Empa tablets 25 mg once daily for 3 months.
Duration: 3 months
Monitoring:
Participants will be followed up by weekly telephone calls and monthly direct meeting at scheduled visits to assess their adherence and to report any drug related adverse effects.
In summary, this clinical trial is designed to determine if empagliflozin is a safe and effective treatment for Rheumatoid Arthritis Patients Treated with Methotrexate by comparing its effects to a placebo and closely monitoring participants throughout the study.
详细描述
Increasing evidence suggests that the nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (NLRP3) inflammasome is involved in the pathogenesis of RA. Anti-citrullinated protein antibodies (ACPA) are a group of autoantibodies against citrullinated proteins/peptides and are biomarkers of RA. ACPA promotes IL-1 production in rheumatoid arthritis by activating the NLRP3 inflammasome. Several studies have shown an upregulation of NLRP3 mRNA and NLRP3-associated proteins in monocytes, macrophages, and dendritic cells in RA patients. Polymorphisms in the NLRP3 gene indirectly reflect the susceptibility, disease severity and treatment effect of RA .
Methotrexate (MTX) is a folic acid antagonist-an antiproliferative drug, as it is known. MTX is a gold-standard antirheumatic agent in the treatment of rheumatoid arthritis, Various side effects may occur during the treatment of inflammatory diseases, ranging from mild to severe side effects and even leading to treatment discontinuation .
The complications of chronic MTX toxicity include kidney injury, hepatotoxicity, mucositis, neurotoxicity, hyperglycemia, hematologic complications and myelosuppression . Chronically MTX-poisoned patient is the one with a long-standing RA or psoriasis/psoriatic arthritis presenting with sudden onset of erosions or ulcers in psoriatic plaques and/or sudden onset of severe mucosal ulceration in the oral cavity with or without diarrhea and fever secondary to infection. Mucosal ulceration was seen in most chronic cases.
The reason that MTX-induced renal dysfunction is a fundamental problem is that renal function in RA patients is already compromised. Because the renal tubules excrete more than 90% of MTX. MTX toxicity is enhanced by drugs that reduce renal elimination, including sulfonamides, aminoglycosides, cisplatin, penicillins, and colchicine, as well as by drugs that displace methotrexate from protein binding sites in plasma, including sulfonamides, phenytoin, retinoids, and barbiturates .
Gastrointestinal side effects of MTX is the main dose-limiting issue for the use of MTX is gastrointestinal toxicity.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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 28 joints disease activity score (DAS-28)
- •Age range between 18 and 60 years old.
- •Both sexes.
- •Body mass index (BMI), age, disease activity, and disease duration matched patients.
排除标准
- •Patients with renal or hepatic diseases (chronic liver disease, liver cirrhosis, alcoholic hepatitis, or chronic alcoholism).
- •Patients receiving biological DMARDs during 4 weeks before the first dose of Empa.
- •Patients with hypersensitivity to study medications.
- •Patients using antioxidants except Empa.
- •Pregnant and lactating females.
- •Pre-existing blood disorders, such as bone marrow hypoplasia, leukopenia, thrombocytopenia, or significant anemia.
- •Patient with HIV/AIDS, blood dyscrasias, or radiotherapy.
研究组 & 干预措施
MTX SC or IM - Empa tab
IM or SC Methotrexate plus Empa tablets 25 mg once dailyf or 3 months.
干预措施: Empagliflozin 25mg tab (Drug)
MTX SC or IM - placebo tab
IM or SC Methotrexate plus placebo tablet once daily for 3 months.
干预措施: MTX SC or IM (Drug)
MTX SC or IM - Empa tab
IM or SC Methotrexate plus Empa tablets 25 mg once dailyf or 3 months.
干预措施: MTX SC or IM (Drug)
结局指标
主要结局
calculation of DAS28-CRP score for measure disease activity
时间窗: From enrollment to the end of treatment at 3 months
this is a score for measure of disease activity in RA ; 2.6 mean RA is in remission 2.6 to 3.2 mean low level of disease activity More than 3.2 mean active disease that may require change in medication More than 5.1 mean very active disease that requires careful monitoring and adjustment to medication
次要结局
- measurement of the levels of Interleukin-1β and Superoxide dismutase(From enrollment to the end of treatment at 3 months)
研究者
Nehad Waleed Karam
Pharmacist and Master's degree student
Tanta University