Is Local Injection of Mesenchymal Stem Cells After Endoscopic Dilation Safe and Does it Improve the Outcome of Intestinal Stricture in Patients With Crohn's Disease?
试验速览
- 阶段
- 2 期
- 入组人数
- 50
- 试验地点
- 1
- 主要终点
- Assessment of safety of local MSCs injection, in association with endoscopic dilation, in strictures of patients with Crohn's disease.
研究概览
简要总结
This is an exploratory phase II study, to evaluate the impact of these Mesenchymal Stem Cells (MSCs) on strictures in Crohn's disease patients with symptomatic intestinal stricture eligible to endoscopic dilatation. The impact of combined treatment by endoscopic dilation and local injection of MSCs will be compared with that of a control group.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patient aged ≥ 18 years with Crohn's Disease diagnosed more than 6 months ago
- •Background treatment, for Crohn's Disease, stable for 4 months
- •Presence of stricture (whether de novo or anastomotic), meeting the radiological definition of stenosis, i.e. a combination of the following criteria: (1) localized luminal narrowing (reduction of luminal diameter by at least less than 50% compared to adjacent healthy bowel segment), (2) bowel wall thickening (25% increase in wall thickness compared to adjacent unaffected bowel) and pre-stenotic dilation (luminal diameter greater than 3 cm)
- •Presence of symptomatic stricture with abdominal pain after meals and limitations on the amount or type of food at screening
- •Presence of a stenosis accessible by ileo-colonoscopy, not passable (i.e. not allowing the passage of the adult ileo-colonoscope), of a length less than 5 cm, eligible for endoscopic dilation
- •Patient accepting the study protocol and having signed an informed consent
- •Patient capable of undergoing entero-MRI
排除标准
- •Patient liable for immediate surgery
- •Patient with intra-abdominal fistula or abscess
- •Patient with a stenosis not accessible to ileocolonoscopy
- •Patient presenting ≥ 2 strictures with impossibility of determining which stenosis is "dominant" and responsible for the symptoms (based on dilation in entero-MRI)
- •Patient with a stenosis longer than 5 cm
- •Patient with a contraindication to performing an entero-MRI or to the use of contrast product injection in entero-MRI (Gadolinium)
- •Pregnant woman or planning a pregnancy in the year
- •Patient with kidney insufficiency (with anuria, glomerular filtration rate < 30 ml/min or on dialysis), hepatic insufficiency (presence of fulminant hepatitis, cirrhosis with signs of portal hypertension, acute alcoholic hepatitis, esophageal varices, history of gastrointestinal bleeding following rupture of esophageal varices, hepatic encephalopathy, prolonged prothrombin time, ascites secondary to portal hypertension, bacterial or fungal liver abscess, biliary obstruction, chronic viral hepatitis with a total serum bilirubin level > 3 mg/dL)
- •Patient with documented human immunodeficiency virus (HIV) infection, active hepatitis B or C or tuberculosis
- •Patient having presented an opportunistic infection in the 6 months preceding inclusion or a serious infection in the previous 3 months
- •Patient who has developed a malignant tumor with a history of lymphoproliferative disease with the exception of: non-melanoma skin cancer, carcinoma in situ (e.g. skin, cervix, bladder, breast) and in remission for at least 3 years prior to screening, superficial bladder cancer, asymptomatic low-grade or localized curatively treated prostate cancer for which the "watch-and-wait" approach is the standard of care as well as any other cancer that has been in remission for ≥ 3 years prior to enrollment.
研究组 & 干预措施
"control" group
One local injection of the placebo (cell-free cell suspension solution devoid of cells) after endoscopic dilatation of the stricture
干预措施: Comparative placebo (Other)
"MSCs" group
One local injection of MSCs (3*10^7 cells) after endoscopic dilatation of the stricture
干预措施: Mesenchymal Stem Cells (Other)
结局指标
主要结局
Assessment of safety of local MSCs injection, in association with endoscopic dilation, in strictures of patients with Crohn's disease.
时间窗: From Week 0 to Week 48
Recording of occurrence of adverse events (serious or not) up to week 48
Assessment of efficacy of local MSCs injection, in association with endoscopic dilation, in strictures of patients with Crohn's disease by evaluating symptomatic clinical response
时间窗: Between Week 0, Week 24 and Week 48
The symptomatic clinical response will be assessed by a composite score, calculated over an average of 7 days, taking up 2 of the 16 questions of the S-PRO or Stenosis Patient Reported Outcome in English (also called Stricturing Crohn's Disease Questionnaire). A score for postprandial abdominal pain \< 2 and an average score, out of 7 days, for amount of types of food \<2 also.
Assessment of efficacy of local MSCs injection, in association with endoscopic dilation, in strictures of patients with Crohn's disease by evaluating endoscopic response
时间窗: Between Week 0, Week 24 and Week 48
The endoscopic response will be defined by the ability to pass an adult colonoscope (complete endoscopic response) or an increase in lumen diameter (partial endoscopic response) measured in comparison with the size of an open biopsy forceps (7mm)
Assessment of efficacy of local MSCs injection, in association with endoscopic dilation, in strictures of patients with Crohn's disease by evaluating radiological response
时间窗: Between Week 0, Week 24 and Week 48
The radiological response will be defined by the presence of 3 of the 4 following criteria: (1) an improvement in luminal narrowing (improvement greater than 50% and/or reduction in luminal diameter of less than 50%); (2) improvement in pre-stenotic dilation (pre-stenotic dilation reduced by 50%, bowel diameter equal to normal bowel and/or pre-stenotic dilation improved to less than 2.5 cm); (3) reduction in wall thickening (50% improvement in gut wall thickening); (4) a reduction in the length of the stricture (50% improvement)
次要结局
- Evaluation of studying, in addition to biomarkers (CRP and fecal calprotectin),(Weeks 0, 4, 12, 24, 36 and 48)
研究者
Sophie Vieujean
Head of Clinic
Centre Hospitalier Universitaire de Liege