Phase 2a Randomised Double-blind Placebo-controlled Trial to Assess Safety, Efficacy of Artesunate & Curcumin in Crohn's Disease Patients, Who Continue to Have Mild to Moderate Disease Activity on an Adequate Dose of Azathioprine
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- Remission of disease
研究概览
简要总结
This is a single center phase 2a, randomised double-blind, placebo-controlled factorial design, proof of concept trial. Patients with Crohn's disease who are on an adequate dose of azathioprine and still continue to active disease (CDAI > 150 and c-reactive protein > 6) will be enrolled. Forty patients will be randomised in a 1:1:1:1 ratio into 4 groups in a 2x2 factorial design to receive artesunate 200 mg PO daily for 2 weeks and / or Curcumin 2 gm PO daily for 3 months or placebo. Treatment Curcumin x 13 weeks Placebo C x 13 weeks Artesunate x 2 weeks Group 1 Group 2 Placebo A x 2 weeks Group 3 Group 4 During the treatment period and follow up period patients will be continued on their regular dose of azathioprine and 5-aminosalicylic acid with no change allowed during the study period. Patients will maintain a daily diary of symptoms and adverse events. Scheduled hospital visits with blood and stool tests will be at baseline, week 1, month 1, month 3 and month 6. Primary endpoint will be remission (defined as CDAI < 150) at 3 months
详细描述
Primary objective: To study the safety, tolerability and efficacy of Artesunate and Curcumin in patients with Crohn's disease, who have ongoing clinical and biochemical evidence of disease activity despite treatment with azathioprine.
Secondary objectives:
- To investigate the effect of artesunate and curcumin on azathioprine metabolites
- To investigate the mechanistic pathways through which artesunate and curcumin act
End points:
Primary endpoints
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Factorial
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
盲法说明
double-blind
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Men or women with a diagnosis of Crohn's disease who are being treated with an adequate, constant dose of azathioprine for at least 3 months (adequate dose is 1 mg/kg in those with low Thiopurine methyltransferase, 2 mg per kg in those with normal Thiopurine methyltransferase)
- •Age 18 to 65 yrs
- •Crohn's disease of mild to moderate activity (CDAI 150 to 450) and c-reactive protein > 6
- •Hemoglobin >9, white blood cells > 3500, platelets > 1,00,000
- •Bilirubin < 3, alanine transaminase < 3x upper limit of normal
- •Glomerular filtration rate >45
- •Normal electrocardiogram
排除标准
- •Pregnancy, women who are planning to get pregnant and those unwilling to use contraception
- •Lactation
- •Bowel surgery with the past 3 months
- •Intra-abdominal abscess
- •Ileostomy or colostomy
- •Change in dose of 5-aminosalicylic acid in the past 4 weeks
- •Use of corticosteroids within the past 4 weeks
研究组 & 干预措施
Artesunate and Curcumin
Artesunate 200 mg PO once a day x 2 weeks. Curcumin 2 gm PO once a day x 13 weeks.
干预措施: Artesunate (Drug)
Artesunate and Curcumin
Artesunate 200 mg PO once a day x 2 weeks. Curcumin 2 gm PO once a day x 13 weeks.
干预措施: Curcumin (Drug)
Artesunate and Placebo C
Artesunate 200 mg PO once a day x 2 weeks. Placebo C x 13 weeks.
干预措施: Artesunate (Drug)
Artesunate and Placebo C
Artesunate 200 mg PO once a day x 2 weeks. Placebo C x 13 weeks.
干预措施: Placebo C (Drug)
Curcumin and Placebo A
Placebo A x 2 weeks. Curcumin 2 gm PO once a day x 13 weeks.
干预措施: Curcumin (Drug)
Curcumin and Placebo A
Placebo A x 2 weeks. Curcumin 2 gm PO once a day x 13 weeks.
干预措施: Placebo A (Drug)
Placebo A and Placebo C
Placebo A x 2 weeks. Placebo C x 13 weeks.
干预措施: Placebo A (Drug)
Placebo A and Placebo C
Placebo A x 2 weeks. Placebo C x 13 weeks.
干预措施: Placebo C (Drug)
结局指标
主要结局
Remission of disease
时间窗: Baseline to 6 months
Remission of disease as defined by a Crohn's Disease Activity Index (CDAI \< 150). The change in response will be studied by studying the change in CDAI after 1 week, 1 month, 3 months and 6 months
次要结局
- Change in tumor necrosis factor-alpha(baseline to 6 months)
- Change in C-reactive protein(baseline to 6 months)
- Change in fecal calprotectin(baseline to 6 months)
- Effect of artesunate and curcumin on azathioprine metabolites(Baseline to 1 week)