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 (BOTOX-TME)

University Hospital of Bordeaux

Status and phase

Terminated

Phase 2

Conditions

Refractory Medical Treatment After Rectal Resection

Low Anterior Resection Syndrome (LARS>20)

Treatments

Drug: BOTOX-A

Study type

Interventional

Funder types

Other

Identifiers

NCT04991688

CHUBX 2020/64

Details and patient eligibility

About

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.

Full 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.

Enrollment

11 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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.