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

NCT ID: NCT04991688

Last Updated: 2023-10-27

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 11 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-09-01
• Study Completion Date: 2023-03-03

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.

Conditions

Low Anterior Resection Syndrome (LARS>20); Refractory Medical Treatment After Rectal Resection

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

BOTOX-A

Group Type: EXPERIMENTAL

BOTOX-A

Intervention Type: DRUG

10 injections of 20 U of toxin will be made into the rectum 5, 10 and 15 cm above the pectinate line. At each level, 3 injections of 20 U will be performed in the submucosa, circumferentially.The last injection is made 20 cm above the pectinate line. Total does not exceed 200U of Botox-A

Interventions

BOTOX-A

10 injections of 20 U of toxin will be made into the rectum 5, 10 and 15 cm above the pectinate line. At each level, 3 injections of 20 U will be performed in the submucosa, circumferentially.The last injection is made 20 cm above the pectinate line. Total does not exceed 200U of Botox-A

Intervention Type: DRUG

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Hospital, Bordeaux

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Eric RULLIER

Role: PRINCIPAL_INVESTIGATOR

University Hospital, Bordeaux

Locations

CHU Bordeaux

Bordeaux, , France

Countries

France

Other Identifiers

CHUBX 2020/64

Identifier Type: -

Identifier Source: org_study_id