A Phase IB/IIA Study of Allogeneic Bone Marrow Derived Mesenchymal Stem Cells for the Treatment of Ileal Anal Anastomosis and Ileal Pouch Fistulas in the Setting of Crohn's Disease of the Pouch
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- 入组人数
- 24
- 试验地点
- 1
- 主要终点
- Treatment related adverse events
研究概览
简要总结
Restorative proctocolectomy with ileal pouch anal anastomosis (IPAA) is the procedure of choice for patients with ulcerative colitis, familial adenomatous polyposis, and select patients with Crohn's disease due to overall low patient morbidity and good quality of life. However, some patients can develop Crohn's disease of the pouch, a clinical diagnosis of Crohn's disease following IPAA. One of the manifestations of Crohn's disease of the pouch includes a fistula from the pouch that travels to the vagina or perianal area. These fistulas can be quite difficult to manage with medications and local surgical intervention, and, on occasion result in a reconstruction pouch but more often require a pouch excision with permanent end ileostomy. The purpose of this study is to evaluate the safety and efficacy of using allogeneic bone marrow derived mesenchymal stem cells to treat people who have a peri-pouch fistula related to a clinical diagnosis of Crohn's disease of the pouch.
详细描述
This aim of this study is to determine the safety and efficacy of adult allogeneic bone marrow derived mesenchymal stem cells (MSCs), for the treatment of medically refractory peri-pouch fistulizing disease in the setting of Crohn's disease of the pouch. The study will randomize 20 participants. Enrolled participants will be randomized to treatment group with MSCs, versus placebo in a 3:1 fashion. Participants in the treatment group will have a direct injection of MSCs at a dose of 75 million cells. This will be given as a direct injection in and around the fistula tract. Participants will be evaluated for complete healing at three months. If complete healing has been achieved participants will continue to be followed for one year. If complete healing has not been achieved at three months, participants will be eligible for a second injection of MSCs at the same dose of 75 million cells. Control participants without complete healing from placebo will cross over at the 6 month visit to receive an injection of MSCs and will be followed for one year after treatment to a total duration of 18 months. The primary efficacy analysis will be conducted at the month 6 time point.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Single (Participant)
盲法说明
Single
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Men and women 18-75 years of age who have undergone an ileal pouch anal anastomosis at least 6 months prior who have developed a clinical diagnosis of Crohn's disease of the pouch as determined by a combination of clinical symptoms, pouchoscopy with biopsy, enterography.
- •Single and multi-tract (up to 2 internal and 3 external openings) fistula tract arising from the ileal pouch, ileal anal anastomosis, or anal canal distal to anastomosis that travels to the perianal skin, perineal body, or vagina. Patients with fistulas that arise from the pouch, anastomosis, or anal canal distal to the anastomosis will both be included in enrollment.
- •Acceptable internal openings and tract locations for the fistula to arise from include the ileal pouch body, the pouch anal anastomosis, and the anal canal distal to the anastomosis.
- •Acceptable external openings and tract locations for the fistula to arise from include the perianal skin, perineal body, and/or the vaginal wall.
- •Concurrent Crohn's related therapies with stable doses (>2 months) corticosteroids, 5-ASA drugs, immunomodulators, anti-TNF therapy, anti-integrin and anti-interleukin are permitted.
- •Have failed conventional medical therapies described above, defined as a lack of response to systemic immune suppression (e.g. azathioprine, methotrexate, 6-mercaptopurine) or biologic (e.g. anti-TNF, anti-integrin, anti-interleukin) therapies to treat fistulizing CD for at least 2 months
- •Have no contraindications to MR evaluations: e.g. pacemaker or magnetically active metal fragments, claustrophobia
- •Competent and able to provide written informed consent
- •Ability to comply with protocol.
排除标准
- •Inability to give informed consent.
- •Severe antibiotic refractory pouchitis
- •Severe cuffitis refractory to antibiotics
- •Change in medical management for CD in the previous 2 months or changes anticipated in the next 2 months
- •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 CBC at screening
- •i. Platelets <50 kg/uL or greater than 1.5 million kg/uL ii. WBC <50 x kg/uL iii. Hbg <7.0 g/dL d. Abnormal AST or ALT at screening(defined as >/= 2x ULN)
- •History of cancer including melanoma (with the exception of localized skin cancers) within one year of screening
- •History of colorectal cancer within 5 years
- •Investigational drug within thirty (30) days of baseline
- •Pregnant or breast feeding or trying to become pregnant
- •Branching fistula tract that has > 2 internal openings or 3 external openings,
- •Subjects with greater than 3 blind/branching tracts are excluded
- •Fistula tracts on the left and/or right side are allowed
- •Allergic to local anesthetics
- •Unwilling to agree to use acceptable contraception methods during participation in study
- •Subjects with a non-abscessed chronic cavity will not be included in enrollment
研究组 & 干预措施
Placebo
Direct injection of normal saline. If not completely healed after 6 months, participants will then cross over to the treatment group to receive a direct injection of allogeneic bone marrow derived mesenchymal stem cells at a dose of 75 million cells into ileal pouch fistula(s).
干预措施: Placebo (Other)
Mesenchymal stem cells
Direct injection of allogeneic bone marrow derived mesenchymal stem cells at a dose of 75 million cells into the ileal pouch fistula(s) at baseline with a possible repeat injection at 3 months if not completely healed from the first injection.
干预措施: Mesenchymal stem cells (Drug)
结局指标
主要结局
Treatment related adverse events
时间窗: Month 6
Number of participants with treatment related adverse events post-injection of 75 million allogeneic bone marrow derived MSC's for the treatment of medically refractory pouch fistulizing disease as assessed by protocol CCF-Stem Cells IBD-002
次要结局
- Partial healing(Month 6, Month 12)
- Complete clinical healing(Month 6, Month 12)
- Lack of response(Month 6, Month 12)
- Worsening disease(Month 6, Month 12)
研究者
Anthony Lembo
Sponsor-investigator
The Cleveland Clinic