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

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

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).

Study Overview

• Status: Recruiting
• Conditions: Low Anterior Resection Syndrome
• Intervention / Treatment: Other: Anal dilatation per anus; Drug: administration of probiotics (Clostridium butyricum TO-A; Bacillus mesentericus TO-A; Streptococcus faecalisT-110) per anus

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 164
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Ruoxu Dou, M.D.; Phone Number: +86-756-2528708; Email: dourx@mail.sysu.edu.cn

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510630
      • Recruiting
      • The Sixth Affiliated Hospital, Sun Yat-sen University
      • Contact: Rongkang Huang, M.D.; Phone Number: 020-13480218647; Email: huangrk3@mail.sysu.edu.cn
    • Zhuhai, Guangdong, China, 519000
      • Recruiting
      • The Fifth Affiliated Hospital, Sun Yat-sen University
      • Contact: Ruoxu Dou, M.D.; Phone Number: 020-13342808275; Email: dourx@mail.sysu.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. A voluntarily signed and dated informed consent form;
2. ECOG Performance status is 0 or 1;
3. Age at enrollment is of 18 to 80 years old.;
4. R0 sphincter-preserving proctectomy and temporary ileostomy for rectal cancer;
5. The distance from anastomosis to anal verge is ≤7cm;
6. Both the anastomosis and the ileostomy is intact at 2 weeks follow-up after proctectomy;
7. Baseline LARS score before proctectomy is <30;
8. The preoperatively predicted LARS (POLARS) score after proctectomy is ≥28.

Exclusion Criteria:

1. R1/R2 resection or untreated metastases;
2. 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;
3. Severe morbidity with life expectancy less than 2 years;
4. Any toxicity of CTCAE grade 2 or above due to previous treatment that have not resolved, except for anemia, alopecia, skin pigmentation;
5. Anastomotic leak within 2 weeks after proctectomy, suspected by clinical symptoms, digital rectal examination, or imaging;
6. Complications of the ileostomy within 2 weeks after proctectomy, leading to premature takedown of the stoma (within 2 months after surgery);
7. Any medical condition that may affect the safety and compliance of the subject.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Sixth Affiliated Hospital, Sun Yat-sen University
• Collaborators: Fifth Affiliated Hospital, Sun Yat-Sen University

Study record dates

Study Major Dates

• Study Start (Actual): February 20, 2021
• Primary Completion (Anticipated): December 31, 2023
• Study Completion (Anticipated): December 31, 2023

Study Registration Dates

• First Submitted: December 13, 2020
• First Submitted That Met QC Criteria: December 24, 2020
• First Posted (Actual): December 29, 2020

Study Record Updates

• Last Update Posted (Estimate): December 6, 2022
• Last Update Submitted That Met QC Criteria: December 2, 2022
• Last Verified: December 1, 2021

More Information

Terms related to this study

• Keywords: rectal cancer; temporary ileostomy; low anterior resection syndrome; anal dilatation; gut microbiota
• Additional Relevant MeSH Terms: Pathologic Processes; Disease; Pathological Conditions, Anatomical; Syndrome; Dilatation, Pathologic
• Other Study ID Numbers: 2020ZSLYEC-187

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No