A New MR-based Perianal Crohn's Disease Activity Score: A Multi-centre Study
试验速览
- 阶段
- 不适用
- 入组人数
- 25
- 试验地点
- 3
- 主要终点
- Primary Outcome
研究概览
简要总结
Perianal Crohn's disease (pCD) is the commonest form of fistulising Crohn's disease, with up to 38% of patients affected and with 30% of them experiencing recurring disease symptoms. Presence of fistula can lead to major morbidity due to cutaneous perianal abscess formation or drainage.
To date, it is very difficult to quantify inflammation in patients with pCD due to the absence of reliable disease activity measurements. In addition to this, optimising therapies for pCD is quite challenging and may have a major impact on quality of life. Magnetic resonance imaging of pelvic is a standard examination for the anatomical evaluation of pCD which is significant in terms of surgical therapy and progress. The overall hypothesis is that newer MRI techniques such as magnetization transfer (MT), diffusion weighted image ( DWI) and dynamic contract enhancement (DCE) are better suited to measuring the inflammatory vs fibrotic burden in pCD. The aim of this project is to measure disease activity within pCD and luminal CD using MRI sequences before and after biological therapy
详细描述
Background:
Inflammatory Bowel Disease has the United Kingdom prevalence of ~620,000 patients. PCD is the commonest form of fistulising Crohn's disease with 20% of patients affected and with 30% of them experiencing recurring disease symptoms. Durable clinical remission rate for complex fistulas is only 37% at the end of a 10-year follow-up.
To this date, it is very difficult to reliably measure disease activity within the fistulas in pCD.
Patients are sometimes needlessly left on long term medical therapy when their pCD has reached a chronic, fibrotic and irreversible stage. This practice needlessly exposes patients to clinical risk and health care systems to the financial expense of up to ~£20k/patient/year. More commonly, medical therapies are stopped prematurely, leading to prompt disease recurrence and chronic fistulisation with a major impact on quality of life. Importantly, it is very difficult to optimise therapies for pCD due to the absence of reliable disease measures. It is not possible to reliably correlate therapeutic drug monitoring to disease activity states. Due to all these limitations there has been an alarming paucity of well-designed randomised clinical trials. To this effect, both the 5th Scientific Workshop on pCD of the European Crohn's and Colitis Organisation and the global consensus on the classification, diagnosis and treatment of pCD by the international Organisation of Inflammatory Bowel disease, have highlighted the urgent need of more sensitive and specific MR-markers of disease activity in pCD. Once reliable MR measures of disease activity have been validated then these can be used to design appropriate, inexpensive, sensitive and non-invasive MR based clinical activity scores.
Various clinical and radiological outcome measures have been investigated to quantify pCD activity. Clinical assessment is crude and participant to inter-operator-variability, with response loosely defined as a reduction of ≥50% in the number of draining fistulas and remission the absence of draining fistulas on two consecutive visits. This assessment has never been validated, and takes no account of the inflammatory state of the disease deep within the perineum. A Perineal Disease Activity Index (PDAI) was developed to assess perianal disease severity and response to therapy. It is based on the assessment of quality of life and disease severity. The PDAI score is 87% accurate and wrongly classifies patients' disease activity in 10% of cases, but is insensitive to change after medical therapy and its remission cut-off never been properly determined.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 16 Years 至 75 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Active perianal Crohn's disease as defined by clinical assessment and a PDAI score of >
- •A clinical decision has been taken to start biological therapy
- •Ages of 16-75
- •No immediate plan for surgery in the near future
- •Ability to consent
- •No obvious contraindication to the use of MR
- •A clear intention by the recruited participant to adhere to the study protocol.
排除标准
- •Immediate surgery planned on the perianal Crohn's disease in the following 12 weeks.
- •Inability to consent
- •history of proctectomy,
- •absence of a diagnosis of Crohn's disease,
- •perianal fistulising disease not secondary to Crohn's disease,
- •rectovaginal fistulas
- •Malignant disease
- •Significant cardiovascular or respiratory disease
- •Neurological or cognitive impairment
- •Significant physical disability
- •Significant hepatic disease or renal failure
- •Abnormal blood results other than those explained by CD
- •Participants currently (or in the last three months) participating in another research project
- •pregnancy or breastfeeding
- •If MRI is contraindicated (e.g. pacemaker
结局指标
主要结局
Primary Outcome
时间窗: At 12 week
1. The difference in the composite MR endpoints between the change in novel MRI parameter (c-f) and the change in standard of care MRI (a-b) from baseline in responders to biological therapy at 12 weeks post-treatment onset at 3T and 1.5T. 1. The number, course and extension of fistulas with active inflammation in the fistula quantified through hypersensitivity in T2-weighted images, rectal wall involvement and presence of abscesses (Van Assche Score) 2. Gadolinium-mediated T1 enhancement. 3. Quantitative dynamic contrast enhancement, 4. Magnetisation transfer and T2 signals 5. Fistula volume 6. Apparent diffusion coefficient in diffusion-weighted MR images
次要结局
- Secondary Outcome measure(At 12 weeks)