Study of Brain-Gut Function Reconstruction After Intersphincteric Resection for Ultra-Low Rectal Tumors

Study Overview
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Brief Summary
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To investigate the effects of intersphincteric resection (ISR) of ultra-low rectal tumor on the brain-rectoanal function of patients, and to precisely localize the cerebral functional regulatory regions for intervention targets of anorectal remodeling. Utilizing transcranial magnetic stimulation(TMS) technology to explore the functional remodeling of the new anorectal muscle groups and provide a theoretical basis for more research on the rehabilitation and mechanism of fecal incontinence.

Detailed Description
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This study is a Single-center Phase II, Open, Three-Arm clinical trial. We prospectively enroll patients who undergo ISR for ultra-low rectal tumor in the department of General Surgery, Huashan Hospital, Fudan University. Patients with ileostomy closure are randomly divided into two groups (TMS group and false stimulation group), and healthy volunteers were recruited. The differences of task-state fMRI between healthy volunteers, and ISR patients (both preoperative and postoperative) are compared, combined with rectal function scores (Wexner score, LARS score) and quality of life scale (EORTC QLQ-C30, EORTC QLQ-CR38). Proctoanal manometry are used to find the precise location of the proctoanal motor function area in the cerebral cortex, and to evaluate the effect and value of TMS on postoperative anorectal motor function remodeling in patients with ISR.

Official Title
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Observation and Intervention Study of Brain-Gut Function Reconstruction After Intersphincteric Resection (ISR) for Ultra-Low Rectal Tumors

Conditions
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Rectal Neoplasms

Intervention / Treatment
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* Device: Transcranial magnetic stimulation
* Device: Sham Transcranial magnetic stimulationt


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Primary ultra-low rectal tumor patient who is received intersphincteric resection and preventive ileostomy was performed. Patient who is willing to participate in the study, and voluntarily sign informed consent. Exclusion Criteria: Anastomotic leakage or other serious complications occur after surgery. Advanced tumor, tumor recurrence or metastasis. Patients with contraindications of fMRI scanning, such as history of metal implants in the body, claustrophobia, etc. Patients with contraindications for TMS treatment, such as intracranial metal implants, epilepsy history, heart disease with unstable heart function, retinal detachment, etc. Combined with organic brain disease and drug abuse history. Combined with other mental diseases. Pregnant or lactating women.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

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
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Sham Comparator: Sham Stimultion Group<br>Patients on the Sham stimulation group will be interfered with the stimulation coil perpendicular to the skull, so that they will hear the sound of machine without having therapeutic effects. The parameters will be the same as those in the stimulation group. | Device: Sham Transcranial magnetic stimulationt<br>* The magnetic stimulator equipment is provided by the MagProX100 magnetic stimulator ( MagVenture, Lucernemarken, DK-3520 Farum, Denmark), with 8-shaped coil, a maximum stimulation frequency of 30Hz and a maximum stimulation intensity of 6 Tesla. Patients on the Sham stimulation group will be interfered with the stimulation coil perpendicular to the skull, so that they will hear the sound of machine without having therapeutic effects. The parameters will be the same as those in the stimulation group.<br>|
| Active Comparator: Pre-ileostomy-closure Stimultion Group<br>Patients on the Pre-ileostomy-closure group will be interfered with stimulation 3 weeks before the procedure of ileostomy closure. | Device: Transcranial magnetic stimulation<br>* The magnetic stimulator equipment is provided by the MagProX100 magnetic stimulator ( MagVenture, Lucernemarken, DK-3520 Farum, Denmark), with 8-shaped coil, a maximum stimulation frequency of 30Hz and a maximum stimulation intensity of 6 Tesla.Stimulation group: Intermittentpulse transcranial magnetic stimulation (iTBS) will be performed with : the cluster consists of 3 pulses, the intra-cluster frequency is 50Hz, the intercluster frequency is 5Hz, the interval is 8.2s for every stimulus. There are 20 cycles and a total of 600 pulses. Each intervention time is 3min11s, and the stimulation intensity is set as 80% resting state motion threshold. The intervention will be performed once a day for 2 weeks.<br>|
| Active Comparator: Post-ileostomy-closure Stimultion Group<br>Patients on the Post-ileostomy-closure group will be interfered with stimulation 3 weeks after the procedure of ileostomy closure. | Device: Transcranial magnetic stimulation<br>* The magnetic stimulator equipment is provided by the MagProX100 magnetic stimulator ( MagVenture, Lucernemarken, DK-3520 Farum, Denmark), with 8-shaped coil, a maximum stimulation frequency of 30Hz and a maximum stimulation intensity of 6 Tesla.Stimulation group: Intermittentpulse transcranial magnetic stimulation (iTBS) will be performed with : the cluster consists of 3 pulses, the intra-cluster frequency is 50Hz, the intercluster frequency is 5Hz, the interval is 8.2s for every stimulus. There are 20 cycles and a total of 600 pulses. Each intervention time is 3min11s, and the stimulation intensity is set as 80% resting state motion threshold. The intervention will be performed once a day for 2 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The differences of cortical activated areas in task-state fMRI in ISR patients. | Cortical activated areas in BOLD sequence of patients in different time frame | pre-ISR, pre-ileostomy closure, 6,12 month after ileostomy closure. | 
| The differences of cortical activated areas in task-state fMRI between health volunteers and postoperative ISR patients. | Cortical activated areas in BOLD sequence of health volunteers and patients | 12 month after ileostomy closure。 | 
| Rectal function scores (Wexner score) | Wexner score of patients in different time frame | pre-ISR，1, 3 , 6, 9, 12, 18, 24 month after ileostomy closure. | 
| Rectal function scores (LARS score) | LARS score of patients in different time frame | pre-ISR，1, 3 , 6, 9, 12, 18, 24 month after ileostomy closure. | 
| Quality of life Scale (EORTC QLQ-C30) | EORTC QLQ-C30 of patients in different time frame | pre-ISR，1, 3 , 6, 9, 12, 18, 24 month after ileostomy closure. | 
| Quality of life Scale (EORTC QLQ-CR38) | EORTC QLQ-CR38 of patients in different time frame | pre-ISR，1, 3 , 6, 9, 12, 18, 24 month after ileostomy closure. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proctoanal manometry | Proctoanal manometry of Patients in different time frame | pre-ISR，3 , 6, 12, 18, 24 month after ileostomy closure. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ultra-low rectal tumors, Intersphincteric Resection, transcranial magnetic stimulation, fMRI