Anal Dilatation Plus Probiotics Before Ileostomy Reduction for Low Anterior Resection Syndrome

Study Overview
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Brief Summary
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This is randomized, phase 2 trial in patients with rectal cancer undergoing sphincter-preserving proctectomy and temporary ileostomy, to explore the effects of anal dilatation plus probiotics administered per anus before ileostomy reduction in relieving postoperative bowel dysfunction known as low anterior resection syndrome (LARS).

Detailed Description
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Approximately 60-90% of patients undergoing sphincter-sparing proctectomy complain of postoperative bowel dysfunction including incontinence, frequency, clustering, and urgency, collectively known as low anterior resection syndrome (LARS). Literatures and our previous data have demonstrated that diverting ileostomy is an independent risk factor for major LARS. This is a randomized, phase 2 trial in patients with rectal cancer who underwent sphincter-preserving proctectomy and ileostomy. This study will explore the effects of anal dilatation plus probiotics administered per anus in relieving the symptoms of LARS.

Official Title
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A Randomized, Phase 2 Study of Anal Dilatation Plus Probiotics Before Ileostomy Reduction for Low Anterior Resection Syndrome After Sphincter-preserving Proctectomy

Conditions
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Low Anterior Resection Syndrome

Intervention / Treatment
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* Other: Anal dilatation per anus
* Drug: administration of probiotics (Clostridium butyricum TO-A; Bacillus mesentericus TO-A; Streptococcus faecalisT-110) per anus


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: A voluntarily signed and dated informed consent form; ECOG Performance status is 0 or 1; Age at enrollment is of 18 to 80 years old.; R0 sphincter-preserving proctectomy and temporary ileostomy for rectal cancer; The distance from anastomosis to anal verge is ≤7cm; Both the anastomosis and the ileostomy is intact at 2 weeks follow-up after proctectomy; Baseline LARS score before proctectomy is <30; The preoperatively predicted LARS (POLARS) score after proctectomy is ≥28. Exclusion Criteria: R1/R2 resection or untreated metastases; Any synchronous or metachronous malignancies, except for cancers that have received curative treatment and have not recurred for more than 5 years, or carcinoma in situ that have been cured by appropriate treatment; Severe morbidity with life expectancy less than 2 years; Any toxicity of CTCAE grade 2 or above due to previous treatment that have not resolved, except for anemia, alopecia, skin pigmentation; Anastomotic leak within 2 weeks after proctectomy, suspected by clinical symptoms, digital rectal examination, or imaging; Complications of the ileostomy within 2 weeks after proctectomy, leading to premature takedown of the stoma (within 2 months after surgery); Any medical condition that may affect the safety and compliance of the subject.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Eligible patients were randomized to the treatment group (anal dilatation plus probiotics) or the control group.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment Arm<br>Anal dilatation plus probiotics per anus Q3D, starting from 2 weeks after proctectomy until reduction of ileostomy. | Other: Anal dilatation per anus<br>* Digital anal dilatation through anastomosis, with concomitant administration of probiotics per anus<br>Drug: administration of probiotics (Clostridium butyricum TO-A; Bacillus mesentericus TO-A; Streptococcus faecalisT-110) per anus<br>* Digital anal dilatation through anastomosis, with concomitant administration of probiotics per anus<br>|
| No Intervention: Control Arm<br>No anal dilatation or probiotics per anus was allowed, from 2 weeks after proctectomy until reduction of ileostomy. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Major LARS at 1 years after proctectomy | Proportion of patients with Low anterior resection syndrome (LARS) score ≥30. LARS score is a tool consisting of five items, which are as follows: incontinence due to flatus (score range from 0 to 7), incontinence due to liquid stools (score range from 0 to 3), frequency of bowel movements (score range from 0 to 5), clustering (score range from 0 to 11) and urgency (score range from 0 to 16). The severity of each item is calculated on a scale ranging from 0 to 42, with a score of 0-20 (no LARS), 21-29 (minor LARS) and 30-42 (major LARS). | At 1 years after proctectomy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| LARS score at 1 years after proctectomy | Low anterior resection syndrome (LARS) score is a tool consisting of five items, which are as follows: incontinence due to flatus (score range from 0 to 7), incontinence due to liquid stools (score range from 0 to 3), frequency of bowel movements (score range from 0 to 5), clustering (score range from 0 to 11) and urgency (score range from 0 to 16). The severity of each item is calculated on a scale ranging from 0 to 42, with a score of 0-20 (no LARS), 21-29 (minor LARS) and 30-42 (major LARS). | At 1 years after proctectomy | 
| Quality of life assessed using the EORTC Quality of Life questionnaire (QLQ)-C30 at 1 years after proctectomy | The European Organisation for Research and Treatment of Cancer (EORTC) developed and validated a 30-item core questionnaire (QLQ-C30) reflecting global QoL in cancer patients. QLQ-C30 comprises five functional scales, three symptom scales, a global health scale/ a quality of life scale, and six single items. All the scales and single item measures range in score from 0-100. A high score represents a higher level of functioning, a high quality of life, and a greater degree of symptoms. | At 1 years after proctectomy | 
| Quality of life assessed using the EORTC Quality of Life questionnaire (QLQ)-CR29 at 1 years after proctectomy | QLQ-CR29 is developed by The European Organisation for Research and Treatment of Cancer (EORTC). It is a validated supplement to the QLQ-C30 specifically designed for assessment of quality of life in colorectal cancer patients. QLQ-CR29 consists of four functional scales and eighteen single items. All the scales range from 0-100. A high score represents a higher level of functioning and a greater degree of symptoms. | At 1 years after proctectomy | 
| MSKCC BFI Score at 1 years after proctectomy | The Memorial Sloan-Kettering Cancer Centre Bowel Function Instrument (MSKCC BFI) score is a validated questionnaire for evaluation of bowel function after sphincter-preserving surgery. It comprises 18 items covering the frequency of various LARS symptoms and is divided into three sub-scales and four single items. It is scored on a 5-point Likert scale ranging from always to never. The sub-scales scores are summarised as: A 6-item frequency sub-scale (6-30), a four-item dietary sub-scale (4-20), and a four-item urgency sub-scale (4-20). A global score can be calculated as the sum of the sub-scale scores. A total score (possible score range 18-90) can be calculated by adding all the item scores (sub-scale scores plus single item scores). A higher score indicates better bowel function. | At 1 years after proctectomy | 
| Presence of stoma at 1 years after proctectomy | Proportion of patients with a stoma due to failure to reduce, or a second stoma after ileostomy reduction is assessed by a professional doctor or nurse at 2 years after proctectomy. | At 1 years after proctectomy | 
| Anastomotic complications within 1 years after proctectomy | Anastomotic complications is assessed by a professional doctor using Common Terminology Criteria for Adverse Events (CTCAE) classification. | Within 1 years after proctectomy | 
| Time for major LARS (≥30) returning to minor or no LARS (<30) after proctectomy | LARS score is assessed every 6 months after proctectomy, and the time for major LARS (≥30) returning to minor or no LARS (<30) is recorded. Low anterior resection syndrome (LARS) score is a tool consisting of five items, which are as follows: incontinence due to flatus (score range from 0 to 7), incontinence due to liquid stools (score range from 0 to 3), frequency of bowel movements (score range from 0 to 5), clustering (score range from 0 to 11) and urgency (score range from 0 to 16). The severity of each item is calculated on a scale ranging from 0 to 42, with a score of 0-20 (no LARS), 21-29 (minor LARS) and 30-42 (major LARS). | Within 1 years after proctectomy | 
| Other complications within 1 years after proctectomy | Other complications is assessed by a professional doctor using Common Terminology Criteria for Adverse Events (CTCAE) classification. | Within 1 years after proctectomy | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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rectal cancer, temporary ileostomy, low anterior resection syndrome, anal dilatation, gut microbiota