Low Anterior Resection Syndrome (LARS>20)Phase 2BOTOX-TMENCT04991688
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
A Phase 2 study testing BOTOX-A in people with Low Anterior Resection Syndrome (LARS>20) and Refractory Medical Treatment After Rectal Resection, run by University Hospital, Bordeaux at 1 site in France.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Low Anterior Resection Syndrome (LARS>20), Refractory Medical Treatment After Rectal Resection
- What is being tested?
- BOTOX-A
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 11 participants
- Where
- 1 siteFrance
- Study dates
- 1 Sep 2021to 3 Mar 2023
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
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- 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
Who cannot join
- 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
Show all 17Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
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
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.
Read the 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
- Being tested
- BOTOX-A
- Keywords
- Rectal surgery, Low Anterior Resection syndrome, Refractory medical treatment, Fecal incontinence
- Medical subject headings
- Low Anterior Resection Syndrome, Fecal Incontinence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BOTOX-ADrug
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
| Study group | Role | What they receive |
|---|---|---|
| BOTOX-A | Experimental | Not described Receives: Drug: BOTOX-A |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of patients with LARS > 20
Measured: At 3 months after injection
Secondary outcomes (11)
Compliance to treatment
Proportion of patients receiving full injections, 10 injections of 20U of toxin. A total of 200U of BOTOX A will be injected
Measured: At 3 months after injection
Tolerance to treatment
Number of patients with adverse events
Measured: At 3 months after injection
Functional outcome with LARS score
The LARS questionnaire (Low Anterior Resection Syndrome) was the primary end-pointy and evaluate bowel function. Five questions regarding incontinence for flatus and liquid stools, frequency, clustering and urgency for defecation are taken into account. The score ranges from 0 to 42 is divides into no LARS (0 to 20 points), minor LARS (21 to 29 points), and major LARS (30 to 42 points)
Measured: At 0, 1, 2, 3 and 6 months
Faecal incontinence with Wexner score
The Wexner score assesses the importance of anal incontinence, it varies from 0 to 20, 20 corresponding to total incontinence
Measured: At 0, 1, 2, 3 and 6 months
Quality of life (QLQ C-30)
The scores of questionnaire QLQ C-30 will be examined
The EORTC QLQ-C30 is a patients self-rating questionnaire that measures physical, role, social, emotional, and cognitive functions as well as overall QoL. Scores can be linearly transformed to provide a score from 0 to 100. Higher scores represent better functioning on the functional scales and a higher level of symptoms of the symptom scales.
Measured: At 0, 1, 3 and 6 months
Quality of life (QLQ CR-29)
The scores of questionnaire QLQ CR-29 will be examined
The EORTC QLQ-CR29 has five functional and 18 symptom scales. Scores can be linearly transformed to provide a score from 0 to 100. Higher scores represent better functioning on the functional scales and a higher level of symptoms of the symptom scales.
Measured: At 0, 1, 3 and 6 months
Evaluation of Anxiety profil (STAI-Y : State-Trait Anxiety Inventory )
For evaluation of Anxiety profil , the "state" instructions is used, which require participants to report how they feel "right now, at this moment," and the "trait" instruction, which ask them to indicate how they "generally"feel. . For each subscales, scores range from 10 to 40, with higher scores correlating with greater state or trait anxiety.
Measured: At 0, 1, 3 and 6 months
Evaluation of manometry
Manometry will measure the pressure in mmHg of the ano-rectal passage, specifically pressures corresponding to the internal and external sphincter, and rectum. The resting pressure and squeeze pressure will be assessed. Sensitivity test to assess first sensation of gas, urge to defecate, and urgency will also be assessed.
Measured: At 0, 1, 3 and 6 months
Evaluation of barostat
Barostat allows the measurement of rectal capacity (ml) and compliance (ml/mmHg). Compliance is a dynamic property of the rectum, calculated from a sigmoid curve of pressure vs volume created by a step wise incremental distention sequence of a balloon placed in the rectum. Compliance of the patient population (post TME surgery) can be compared to compliance of non-operated rectums from published data. The investigators anticipate that our patient population will have a less compliant neo-rectum and hope to see a difference after Botox-A injection
Measured: At 0, 1, 3 and 6 months
Proportion of patients with LARS ≤ 20
Measured: At 6 months
Correlation between LARS and physiologic tests
The correlation of objective physiologic measures such as manometry and barostat will be compared and correlated to the symptoms described by the patient in the LARS questionnaire before and after injection of Botox-A in the neo-rectum.The investigators anticipate a correlation of increased compliance in the neo rectum with improvement of symptoms (lower LARS score) post Botox-A injection
Measured: At 0, 1, 2, 3 and 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Aug 2021
- Study start1 Sep 2021
- Primary completion7 Jan 2023
- Study completion3 Mar 2023
Why it stopped: Organizational difficulties
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Low Anterior Resection Syndrome (LARS>20)Studies of the same condition, open and under way.
- More trials run by University Hospital, BordeauxThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 11 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Bordeaux
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Eric RULLIER, Principal investigator, University Hospital, Bordeaux
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04991688
- Sponsor's protocol ID
- CHUBX 2020/64
- Acronym
- BOTOX-TME
- Status last verified
- Oct 2023
- First submitted
- 25 Jun 2021
- Last updated
- 27 Oct 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Oct 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04991688
- Acronym / sponsor ID
- BOTOX-TME / CHUBX 2020/64
- 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
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Organizational difficulties
- Enrolment
- 11 participants (actual)
- Lead sponsor
- University Hospital, BordeauxUniversity, hospital or other
- Study start
- 1 Sep 2021 (actual)
- Primary completion
- 7 Jan 2023 (actual)
- Study completion
- 3 Mar 2023 (actual)
- First posted
- 5 Aug 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| BOTOX-A | Experimental | Drug: BOTOX-A |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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
Key exclusion criteria (17 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BOTOX-A10 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 | Drug | BOTOX-A |
Primary outcome
Proportion of patients with LARS > 20
Time frame: At 3 months after injection
11 secondary outcomes
Compliance to treatment
Time frame: At 3 months after injection
Tolerance to treatment
Time frame: At 3 months after injection
Functional outcome with LARS score
Time frame: At 0, 1, 2, 3 and 6 months
Faecal incontinence with Wexner score
Time frame: At 0, 1, 2, 3 and 6 months
Quality of life (QLQ C-30)
Time frame: At 0, 1, 3 and 6 months
Quality of life (QLQ CR-29)
Time frame: At 0, 1, 3 and 6 months
Evaluation of Anxiety profil (STAI-Y : State-Trait Anxiety Inventory )
Time frame: At 0, 1, 3 and 6 months
Evaluation of manometry
Time frame: At 0, 1, 3 and 6 months
Evaluation of barostat
Time frame: At 0, 1, 3 and 6 months
Proportion of patients with LARS ≤ 20
Time frame: At 6 months
Correlation between LARS and physiologic tests
Time frame: At 0, 1, 2, 3 and 6 months
Results and safety
The study was stopped early (reason given: Organizational difficulties). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Oct 2023.
- Individual participant dataSharing planned: No
Related trials for Low Anterior Resection Syndrome (LARS>20)
Not yet recruiting
Efficacy of a Novel High Intensive Percutaneous Tibial Nerve Stimulation on Faecal Incontinence in Patients With Low Anterior Resection Cancer Syndrome After Rectal Cancer Surgery
Faecal Incontinence With Faecal Urgency, Rectal Cancer
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Eric RULLIER principal investigator
University Hospital, Bordeaux
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing BOTOX-A in people with Low Anterior Resection Syndrome (LARS>20) and Refractory Medical Treatment After Rectal Resection, run by University Hospital, Bordeaux at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 27 Oct 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Organizational difficulties). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion of patients with LARS > 20 (time frame: At 3 months after injection). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Oct 2023.