Tolerance of local administration of cryopreserved autologous stromal vascular fraction combined with micrograft for the treatment of refractory ano-perineal fistulas in Crohn's disease
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 25
- 试验地点
- 2
- 主要终点
- Absence of local infectious complications, defined by the absence of local inflammatory signs: pain, and/or erythematous placard, and/or swelling or induration at 6 months, cumulating all assessments at each visit (1 week and at 1, 3 and 6 months).
研究概览
简要总结
To evaluate the overall safety profile of cryopreserved autologous VSF injection combined with autologous microfat in the treatment of refractory anoperineal fistulas associated with Crohn's disease.
入排标准
- 年龄范围
- 18 years 至 65+ years（65+ Years, 18-64 Years）
- 接受健康志愿者
- 否
入选标准
- •Signature of a consent form.
- •Women of childbearing age must have a negative pregnancy test (serum or urine) (detection threshold: 25 mIU hCG/ml). Patients of both sexes should use reliable contraception.
- •Affiliation to a social security system.
- •Patients with Crohn's disease diagnosed at least 6 months previously, according to clinical, endoscopic, histological and/or radiological criteria.
- •Patients previously included/treated in the ADICROHN 2 study.
- •Luminal non-active or weakly active Crohn's disease, defined by a CDAI score ≤
- •Patients with ADICROHN-2 protocol response failure, defined by persistence of anoperineal fistula(s) at the end of the ADICROHN-2 study and their persistence at the time of inclusion.
- •Successful patients (combined remission) at the end of the ADICROHN-2 study but with recurrence of the anoperineal fistula(s) at the time of inclusion.
- •Sufficient quantity of cryopreserved cells to enable innovative treatment, at a rate of at least 30 million frozen cells per fistula pathway based on the number of fistulas to be treated.
- •Patients over 18 years of age.
- •Good general health according to history and clinical examination.
排除标准
- •Active, mainly luminal Crohn's disease requiring immediate treatment.
- •Treatment with darvadstrocel < 6 months prior to inclusion.
- •Contraindications to general anesthesia.
- •BMI < 18 kg/m2 to ensure sufficient abdominal or other subcutaneous adipose tissue accessible by manual liposuction.
- •Coagulation disorders contraindicating surgery.
- •Known hypersensitivity to human albumin.
- •Participation in another clinical trial (other than an observational study).
- •Persons protected by articles L1121-5, L1121-6 and L1121-8 of the French Public Health Code (pregnant or breast-feeding women, persons deprived of their liberty by court order, socially vulnerable persons, adults incapable or unable to give consent).
- •Patient with intolerance to advanced therapy drug in ADICROHN-2 study.
- •Presence of abscess or collections > 2 cm at time of inclusion, unless resolved during fistula preparation.
- •Rectal and/or anal stenosis and/or active rectitis resulting in limited surgical access.
- •Patients on corticosteroids or having received them in the four weeks preceding injection of the experimental product.
- •Malignant tumors or history of malignant tumors less than 5 years old.
- •Congenital or acquired immunodeficiency.
- •Contraindications to local anesthetics and gadolinium (MRI contrast agent).
- •Contraindications to MRI: metallic foreign bodies (ferromagnetic material) and metallic implants (pacemakers, heart valves, vascular clips, surgical clips or staples, cochlear implants, any implanted electronic medical equipment or devices (e.g. insulin pumps), orthopedic medical prostheses.
结局指标
主要结局
Absence of local infectious complications, defined by the absence of local inflammatory signs: pain, and/or erythematous placard, and/or swelling or induration at 6 months, cumulating all assessments at each visit (1 week and at 1, 3 and 6 months).
Absence of local infectious complications, defined by the absence of local inflammatory signs: pain, and/or erythematous placard, and/or swelling or induration at 6 months, cumulating all assessments at each visit (1 week and at 1, 3 and 6 months).
The absence of general infectious complications, defined by the absence of general infectious signs: fever, chills, mottling, hypotension at 6 months, cumulating all assessments at each visit (1 week and at 1, 3 and 6 months).
The absence of general infectious complications, defined by the absence of general infectious signs: fever, chills, mottling, hypotension at 6 months, cumulating all assessments at each visit (1 week and at 1, 3 and 6 months).
No increase in anal incontinence compared with the pre-therapeutic evaluation, as assessed by the Wexner index at 6 months, cumulating all assessments at each visit (1 week and at 1, 3 and 6 months).
No increase in anal incontinence compared with the pre-therapeutic evaluation, as assessed by the Wexner index at 6 months, cumulating all assessments at each visit (1 week and at 1, 3 and 6 months).
The absence of any other adverse events considered potentially related to the experimental treatment at 6 months, cumulating all assessments at each visit (1 week and at 1, 3 and 6 months).
The absence of any other adverse events considered potentially related to the experimental treatment at 6 months, cumulating all assessments at each visit (1 week and at 1, 3 and 6 months).
次要结局
- Remission induced by cryopreserved FVS injection is assessed at 6 months and defined by closure of the external os and absence of collection > 2cm on MRI (= combined remission).
- Remission induced by injection of a second dose of FVS is assessed at 6 months and defined by closure of the external os and absence of collection > 2cm on MRI (= combined remission)..
- Tolerability of a second dose of FVS is defined by evaluation of the overall tolerance profile (see primary endpoint). It is assessed at 6 months as for the primary endpoint.
- Complete clinical response is assessed at 1 week, 1, 3 and 6 months, and defined by the cessation of suppurations.
- Partial clinical response is assessed at 1 week, 1, 3 and 6 months and defined by significant reduction in suppuration (reduction ≥ 2 points on the 5-point suppuration scale).
- Quality of life is assessed at 1, 3 and 6 months using the Short Inflammatory Bowel Disease Questionnaire (SIBDQ).
- Severity of perineal damage is assessed at 1 week and at 1, 3 and 6 months using the Perineal Disease Activity Index (PDAI).
- Patients' disease activity is assessed at 1, 3 and 6 months by the Crohn's Disease Activity Index (CDAI), and at 6 months by fecal calprotectin.
- Closure of the external ostium is assessed at 1 week and at 1, 3 and 6 months, and defined by healing of the ostium or absence of suppuration despite slight digital compression.
研究者
Lucas GUILLO
Scientific
Centre Hospitalier Regional De Marseille