A Prospective Pilot Study to Assess the Efficacy of Botox-A in Patients With Low Anterior Resection Syndrome (LARS>20) and Refractory Medical Treatment After Rectal Resection
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- 入组人数
- 11
- 试验地点
- 1
- 主要终点
- Proportion of patients with LARS > 20
研究概览
简要总结
After rectal resection for cancer (with or without stoma), patients may have digestive sequelae. LARS (Low Anterior Resection Syndrome) includes bowel frequency, stool fragmentation, urgency, and faecal incontinence. The goal of this study is to test intra-rectal BOTOX-A on functional outcomes and quality of life of patients with LARS refractory to medical treatment at 3 months after surgery.
详细描述
Bowel dysfunction after low anterior resection (rectal excision) is referred as Low Anterior Resection Syndrome (LARS). LARS includes bowel frequency, stool fragmentation, urgency, and faecal incontinence. LARS negatively affects patients' quality of life by impacting emotional, physical, social, and role functioning. Symptoms may persist up to 15 years after surgery.
The treatment options for LARS include successively conservative options, as medical drugs and biofeedback, and aggressive options, as retrograde colonic washout, sacral neuromodulation, antegrade colonic enema via a caecostomy, or a definitive colostomy. The effectiveness of conservative treatment remains uncertain and the aggressive treatments are associated with daily constraints and potential morbidity. These findings highlight the need for more efficient treatments BOTOX-A is a neurotoxin inhibiting acetylcholine release at the neuromuscular junction. BOTOX-A has displayed significant benefits in patients with urinary incontinence, demonstrating significant efficacy as compared to placebo. Intra-rectal injections of Botox-A has been trialed for the treatment of over active rectum induced fecal incontinence. Improvement of symptoms and quality of life have been demonstrated. Currently an ongoing national multicenter trial in France, IF Toxine (N° CLINICAL TRIAL: NCT02414425), has included 200 patients to assess Botox-A intra-rectal injections as a treatment option for fecal incontinence, without any safety concerns observed.
The investigators anticipate that BOTOX-A injections could represent a medical option to treat digestive dysfunction (LARS) after surgery for rectal cancer, by reducing the spasm of the smooth muscle in the colon working as a neorectum.
Globally 50% of patients were refractory to medical treatment (LARS score > 20) at 3 months after surgery. Of those, only 30% of them were improved by prolonged medical treatment between 3 and 6 months. The investigators anticipate that 60 % of them will be improved by association of medical treatment and BOTOX-A injection.
The objective is to assess the efficacy of BOTOX-A on the proportion of patients with bowel dysfunction (LARS score > 20) at 3 months after 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
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patient: male and female, age ≥18 years
- •Tumour: rectal cancer
- •Surgery: anterior resection (high or low) with colorectal or coloanal anastomosis, or intersphincteric resection, or pull-through
- •Symptoms: Low Anterior Resection Syndrome (LARS score >20) refractory to medical treatment at 3 months after rectal surgery (or after temporary stoma closed)
- •Straight or pouch colonic reconstruction
- •Surgery alone or with neoadjuvant therapy (chemoradiotherapy, short course radiotherapy, induction chemotherapy)
- •Signed and dated informed consent
- •Patient affiliated to a social security system or beneficiary of the same
- •Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures
排除标准
- •Anal cancer
- •Anal surgery in the last 3 months
- •Acute/painful perianal disease
- •Ongoing adjuvant treatment
- •Contraindication for BOTOX-A (known hypersensitivity to botulinum toxin type A or to albumin, infection at the proposed injection site, severe myasthenia)
- •Have received BOTOX-A in perianal region in the previous 3 months
- •General anesthesia performed less than a month
- •Impossibility of performing a rectoscopy (eg: anal stenosis)
- •Recent history (<12 months) of myocardial infarction and / or arrhythmias not reduced by appropriate treatment
- •Subject with a significant deficit of clinical or subclinical neuromuscular transmission (myasthenia or Lambert-Eaton syndrome) or with peripheral motor neuropathy (such as amyotrophic lateral sclerosis or motor neuropathy)
- •Treatment that directly or indirectly interferes with neuromuscular transmission (aminoglycosides, curare, anticholinesterase, aminoquinoline, cyclosporine, etc.)
- •History of neuromuscular disorders
- •Anal clinical examination suggesting the presence of an anorectal abscess
- •Pregnant woman or breastfeeding woman
- •Women of child-bearing potential (WOCBP)* not using effective contraception (oestrogen-progesteron combined contraceptives or intra uterine device) since at least 7 days and during all the duration of the study
- •Persons deprived of their liberty or under measure of judicial protection (curatorship or guardianship) or unable to give their consent
- •Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol or follow-up schedule, as assessed by investigator.
研究组 & 干预措施
BOTOX-A
干预措施: BOTOX-A (Drug)
结局指标
主要结局
Proportion of patients with LARS > 20
时间窗: At 3 months after injection
次要结局
- Tolerance to treatment(At 3 months after injection)
- Compliance to treatment(At 3 months after injection)
- Quality of life (QLQ CR-29)(At 0, 1, 3 and 6 months)
- Quality of life (QLQ C-30)(At 0, 1, 3 and 6 months)
- Evaluation of Anxiety profil (STAI-Y : State-Trait Anxiety Inventory )(At 0, 1, 3 and 6 months)
- Faecal incontinence with Wexner score(At 0, 1, 2, 3 and 6 months)
- Evaluation of manometry(At 0, 1, 3 and 6 months)
- Functional outcome with LARS score(At 0, 1, 2, 3 and 6 months)
- Proportion of patients with LARS ≤ 20(At 6 months)
- Correlation between LARS and physiologic tests(At 0, 1, 2, 3 and 6 months)
- Evaluation of barostat(At 0, 1, 3 and 6 months)