A Phase I Study of Adult Allogeneic Bone Marrow Derived Mesenchymal Stem Cells for Pediatric Perianal Fistulizing Crohn's Disease
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- 入组人数
- 6
- 试验地点
- 1
- 主要终点
- Treatment related adverse events
研究概览
简要总结
This study plans to enroll 10 patients aged 13-17 years of age with refractory perianal fistulizing disease. Patients will be treated by direct injection to the fistula tract(s) with 75 million allogeneic bone marrow derived mesenchymal stem cells at baseline and again after 3 months if not completely healed.
详细描述
Crohn's disease (CD), a chronic transmural inflammatory disease of the gastrointestinal tract, continues to increase in incidence for unknown reasons. According to population based studies, at least 26% of patients with CD will develop perianal fistulas in the first two decades following diagnosis, particularly those with colonic and rectal involvement. These patients experience significant morbidity due to pain, persistent drainage, recurrent perianal sepsis, and ongoing need to access medical care resulting in increased costs and impaired quality of life. Onset of Crohn's disease in childhood is associated with even more aggressive perianal fistula development, with fistulas occurring in as many as 20-31% of children within 5-7 years after Crohn's disease diagnosis. Based on national estimates of pediatric Crohn's disease prevalence, this suggests that there are more than 10,000 children with perianal fistulas due to Crohn's disease in the United States.
This study plans to enroll 10 patients (aged 13-17 years) with refractory perianal fistulizing disease. The next step in management for these patients would be a mucosal tissue flap, temporary stoma, or proctectomy with permanent ostomy.
Patients will be treated by direct injection of 75 million allogeneic bone marrow derived mesenchymal stem cells at baseline and again after 3 months if not completely healed. Patients will be followed for a total of 12 months post initial injection.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 13 Years 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Males and females aged 13-17 with a diagnosis of Crohn's disease for at least six months duration.
- •Single and Multi-tract Perianal fistula, with or without previous failed surgical repair.
- •Have no contraindications to MR evaluations: e.g. pacemaker or magnetically active metal fragments, claustrophobia
- •Ability to comply with protocol
- •Competent and able to provide written informed consent
- •Concurrent Crohn's-related therapies with stable doses corticosteroids, 5- ASA drugs, immunomodulators, anti-TNF therapy, anti-integrin and anti-interleukin therapies are permitted.
- •Agree to use birth control or abstinence to avoid pregnancy during the study
排除标准
- •Inability to give informed consent.
- •Clinically significant medical conditions within the six months before administration of MSCs: e.g. myocardial infarction, active angina, congestive heart failure or other conditions that would, in the opinion of the investigators, compromise the safety of the subject.
- •Specific exclusions:
- •Hepatitis B or C
- •Abnormal AST or ALT at screening (defined as >/+2x ULN)
- •History of colon cancer in the past two years, or treatment for other cancers within the last 6 months.
- •Investigational drug within one month of treatment
- •Pregnant or breast feeding or trying to become pregnant.
- •Presence of a rectovaginal or perineal body fistula
- •Change in Crohn's immunosuppressive regimen within the 2 months prior to enrollment
- •Uncontrolled intestinal Crohn's disease which will require escalation for medical therapy or surgery within 2 months of enrollment
- •Severe anal canal disease that is stenotic and requires dilation
- •Female participant unwilling to agree to use acceptable contraception methods during participation in study
研究组 & 干预措施
Mesenchymal stem cells
allogeneic bone marrow derived mesenchymal stem cells
干预措施: Mesenchymal stem cells (Drug)
结局指标
主要结局
Treatment related adverse events
时间窗: Month 12
Number of participants with treatment related adverse events post-injection of 75 million allogeneic bone marrow derived MSC's for the treatment of perianal fistula(s) in the setting of Crohn's disease as assessed by protocol
Treatment related adverse events
时间窗: Month 3
Number of participants with treatment related adverse events post-injection of 75 million allogeneic bone marrow derived MSC's for the treatment of perianal fistula(s) in the setting of Crohn's disease as assessed by protocol
次要结局
- Complete clinical healing(Month 12)
- Lack of response(Month 12)
- Worsening of disease(Month 12)
- Partial clinical healing(Month 12)
- Complete clinical healing(Month 3)
- Partial clinical healing(Month 3)
- Lack of response(Month 3)
- Worsening of disease(Month 3)
研究者
Anthony Lembo
MD
The Cleveland Clinic