Autologous Adipose-derived Stem Cells (ASCs) for the Treatment of Perianal Fistula in Crohn Disease: A Pilot Study
试验速览
- 阶段
- 2 期
- 发起方
- 入组人数
- 10
- 试验地点
- 2
- 主要终点
- Healing fistula
研究概览
简要总结
Crohn's disease is an immunologically mediated inflammatory bowel disease with a reported incidence of 4.0-7.0, 7.1, and 1.34 per 100,000 persons in Europe, the U.S., and Korea, respectively. Uncontrolled chronic inflammation finally causes various complications in intestine such as bowel obstruction, fistulas, abscesses, and anal fissures.
The incidence of perianal fistula was reported in 13%- 39% of patients with Crohn's disease. Medical treatment for Crohn's fistulae initially focused on surgical intervention accompanied by symptomatic treatment with antibiotics and immunosuppressants. The most serious problem after surgical intervention is the relatively high incidence of postoperative anal incontinence caused by sphincter injury during the procedure. Conversely, available pharmacological therapies for Crohn's fistulae based on biologic agents such as infliximab do not generally reach ideal goal of treatment (e.g., complete closure of the fistula). A high recurrence rate after treatment with infliximab has also been reported, even after long-term maintenance therapy, which suggests that infliximab monotherapy does not provide adequate healing.
The ACCENT II study demonstraded a complete fistula healing in 25% of patients. To reach a better clinical outcome, combination treatment with infliximab and surgical intervention is highly recommended for management of Crohn's fistulae. Nonetheless, even this strategy does not result in a satisfactory healing for many patients.
The ideal therapeutic goal of treatment is not only complete closure of the fistula without recurrence but also preservation of anal sphincter function. Unfortunately, currently available medical or surgical treatment is not likely to offer a cure for perianal fistulae and, as noted above, recurrence is frequently reported.
Together with active research in the field of bone marrow-derived mesenchymal stem cells (BM-MSCs) and hematopoietic stem cells, autologous or allogenic adipose tissue-derived stem cells (ASCs) have been studied for management of Crohn's disease and other disorders.
Of particular relevance to this study, ASCs could be considered to be safe and efficacious therapeutic tools for the treatment of Crohn's fistulae. Importantly, ASCs do not cause fecal incontinence after injection into the lesion site in Crohn's disease patients. A phase I dose-escalation clinical study with ASCs manufactured by Anterogen Co., Ltd. (Seoul, Korea) demonstrated the safety and therapeutic potential of these cells for the treatment of Crohn's fistulae. A phase II study demonstrated a good rate of cronh's related fistula closure using a ASCS injection.
Actually the best accepted treatment of Crohn related perianal fistula, is the surgical procedure in association whit medical therapy.
详细描述
Basic information:
Lipogems: Lipogems® system is a disposable device for liposuction, processing and adipose tissue reinjection. Procedure takes place in a single surgical time. It's a disposable device that progressively reduces adipose tissue clusters size, washing completely pro-inflammatory oil and blood debrides through a minimal manipulation "free enzyme" in a aseptic closed system completely prefilled by room temperature physiological solution.
Lipogems product is a non-expanded and microfractured fat tissue ready for autologous settings.
SalveColl-E: Salvecoll® is sterile bioplastic, equine derived, type I collagen material with a fully preserved fibrous structure (non-reconstructed) that ensures the regeneration of affected tissues. Type I collagen has zero risk of transmitting viral or microbial infections.
Rationale for the trial: To evaluate the efficacy of the use of ACSS in crohn related perianal fistulas. The aim of the study is to improve fistula healing at 1 year from 25% to 65%.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
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
- •Patients aged > 18 years old
- •Diagnosis of perianal fistulae associated with Crohn's disease.
排除标准
- •Patients aged < 18 years old
- •Informed consent refusal
- •Medical or family history of variant Creutzfeldt-Jakobs disease
- •Activated sever Crohn's disease
- •Perianal fistulae >2 cm in diameter
- •Autoimmune disease or inflammatory bowel disease other than Crohn's disease
- •Infectious disease including hepatitis B virus, hepatitis C virus and immunodeficiency virus infection
- •Active tuberculosis
- •Signs of septicemia
- •Patients treated with Infliximab within 3 months prior to ASC treatment.
- •Technically difficult adipose tissue collection due to low levels of fat tissue.
- •Pregnancy
结局指标
主要结局
Healing fistula
时间窗: 62 weeks
次要结局
- Morbidity(62 week)
- Quality of life modification(62 week)
- Relation between Crohns Disease Activity Index and fistula healing(62 week)
- Mortality(62 week)
研究者
Paolo Bertoli
MD
Papa Giovanni XXIII Hospital