Clinical trial NCT04991688: 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
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Low Anterior Resection Syndrome (LARS>20)
Refractory Medical Treatment After Rectal Resection
Keywords: Rectal surgery
Low Anterior Resection syndrome
Refractory medical treatment
Fecal incontinence
Lead sponsor: University Hospital, Bordeaux
Sponsor class: OTHER
First posted: 2021-08-05
Enrollment: 11
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Proportion of patients with LARS > 20
timeFrame: At 3 months after injection
Secondary outcomes:
measure: Compliance to treatment
timeFrame: At 3 months after injection
measure: Tolerance to treatment
timeFrame: At 3 months after injection
measure: Functional outcome with LARS score
timeFrame: At 0, 1, 2, 3 and 6 months
measure: Faecal incontinence with Wexner score
timeFrame: At 0, 1, 2, 3 and 6 months
measure: Quality of life (QLQ C-30)
timeFrame: At 0, 1, 3 and 6 months
measure: Quality of life (QLQ CR-29)
timeFrame: At 0, 1, 3 and 6 months
measure: Evaluation of Anxiety profil (STAI-Y : State-Trait Anxiety Inventory )
timeFrame: At 0, 1, 3 and 6 months
measure: Evaluation of manometry
timeFrame: At 0, 1, 3 and 6 months
measure: Evaluation of barostat
timeFrame: At 0, 1, 3 and 6 months
measure: Proportion of patients with LARS ≤ 20
timeFrame: At 6 months
measure: Correlation between LARS and physiologic tests
timeFrame: At 0, 1, 2, 3 and 6 months
Other outcomes:
Locations:
city: Bordeaux
country: France
facility: CHU Bordeaux
Study officials:
affiliation: University Hospital, Bordeaux
name: Eric RULLIER
role: PRINCIPAL_INVESTIGATOR
References: