Effectiveness of Sacral Neuromodulation in Low Anterior Resection Syndrome (SANLARS)

Prospective Randomized Cross-over Trial to Assess the Effectiveness of Sacral Neuromodulation in Low Anterior Resection Syndrome. SANLARS Trial (SAcral Neuromodulation for Low Anterior Resection Syndrome)

Low anterior resection syndrome (LARS) is a complex disorder suffered by patients who undergo rectal resection mainly due to rectal cancer. It is characterized by fecal incontinence, fragmented defecation, constipation, defecatory urgency among others, which induce an impairment in quality of life.

LARS treatment armamentarium is scarce and with no long-term relief, being a difficult challenge for surgeons. There is evidence showing that sacral neuromodulation (SNM) improves patients' symptoms and quality of life. However, no prospective randomized studies have supported this improvement.

This is a prospective randomized cross-over study which evaluates the effectiveness of SNM in LARS, specifically analyzing intestinal, urinary, sexual symptoms as well as quality of life.

Study Overview

• Status: Completed
• Conditions: Low Anterior Resection Syndrome; Rectal Cancer; Sacral Neuromodulation - Interstim Therapy
• Intervention / Treatment: Device: Sacral neuromodulation

• Study Type: Interventional
• Enrollment (Actual): 45
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Spain
  • Barcelona, Spain
    • Hospital Universitari Vall d'Hebron Research Institute

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:

• Patients who have had an anterior rectal resection with sphincter preservation by any approach, with or without preoperative radiotherapy.
• Patients with symptomatology of major anterior resection syndrome (>29 points on LARS score) including fecal incontinence, defecatory urgency, fecal fragmentation.
• Period greater than one year since the last definitive surgery (rectal resection or ileostomy closure).
• Period longer than one year in cases in which any other type of therapy has been performed for the anterior resection syndrome (for example: biofeedback, posterior tibial stimulation, physiotherapy, etc).

Exclusion Criteria:

• Patients who refuse to sign informed consent or are unable to understand the study.
• Patients with progression of the oncological disease.
• Patients in initial stage IV (metastatic).
• Patients with inflammatory bowel disease.
• Patients with known irritable bowel prior to rectal surgery.
• Patients who have undergone resection of other intestinal segments.
• Patients with systemic neurological diseases with involvement of long pathways or spinal cord injury.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Sham Comparator: Arm OFF-ON; Patients are subjected to a test phase by stimulation with an external temporal generator and, if there is improvement in their symptomatology, a subcutaneous impulse generator for sacral neuromodulation is implanted. Once the generator is placed it will be disconnected for 4 weeks. Then it will be continued to be turned OFF for 2 weeks as a wash-out period. Then, the stimulator will be turn ON for 4 weeks and will be left on afterwards at the maximum subsensory stimulus. Specific scales will be passed after each sequence crossing.	Device: Sacral neuromodulation; After the definitive implantation, stimulators are placed in position OFF for the first arm and in position ON for the second arm during 4 weeks. Then all the stimulators are switched OFF (both first and second arms) for 2 weeks. Finally stimulators are maintained in position ON for the first arm and switched OFF for the second arm during 4 weeks. Since this is a cross-over study, patients can be randomly assigned to any arm first, but they will go to the other arm since the patient is its own control. 50% of randomized patients will go through ON-OFF and the other 50% OFF-ON. After this cross-over phase, ALL stimulators will be in ON position until the end of the study period.; Other Names: InterStim Therapy
Active Comparator: Arm ON-OFF; Patients are subjected to a test phase by stimulation with an external temporal generator and, if there is improvement in their symptomatology, a subcutaneous impulse generator sacral neuromodulation is implanted. Once the generator is placed it will be turned ON for 4 weeks at the maximum subsensory stimulus. Then it will be turned OFF for 2 weeks as a wash-out period. Then, the stimulator will be kept OFF for 4 weeks. After this sequence it will be turned on again and will be left on afterwards at the maximum subsensory stimulus. Specific scales will be passed after each sequence crossing.	Device: Sacral neuromodulation; After the definitive implantation, stimulators are placed in position OFF for the first arm and in position ON for the second arm during 4 weeks. Then all the stimulators are switched OFF (both first and second arms) for 2 weeks. Finally stimulators are maintained in position ON for the first arm and switched OFF for the second arm during 4 weeks. Since this is a cross-over study, patients can be randomly assigned to any arm first, but they will go to the other arm since the patient is its own control. 50% of randomized patients will go through ON-OFF and the other 50% OFF-ON. After this cross-over phase, ALL stimulators will be in ON position until the end of the study period.; Other Names: InterStim Therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of Responders of Low Anterior Resection Syndrome	Low Anterior Resection Syndrome Score (LARS Score). This is a validated specific score for low anterior resection syndrome which ranges from 0 points (normal - best score) to 42 point (LARS major - worst score). Patients should achieve 50% reduction from basal score.	3 months
Proportion of Responders of Low Anterior Resection Syndrome	Low Anterior Resection Syndrome Score (LARS Score). This is a validated specific score for low anterior resection syndrome which ranges from 0 points (normal - best score) to 42 point (LARS major - worst score). Patients should achieve 40% reduction from basal score.	6 months
Proportion of Responders of Low Anterior Resection Syndrome	Low Anterior Resection Syndrome Score (LARS Score). This is a validated specific score for low anterior resection syndrome which ranges from 0 points (normal - best score) to 42 point (LARS major - worst score). Patients should achieve 40% reduction from basal score.	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fecal incontinence	Fecal continence will be assessed by the St Mark's-Vaizey continence scale, ranging from 0 points (normal - no incontinence, best result) to 24 points (total incontinence, worst result). Changes will be compared to basal data	3 months, 6 months and 12 months
Quality of life in patients with cancer	Validated Quality of life Quality of life questionnaire score developed by the European Organization for Research and Treatment of Cancer (EORTC) named QLQ-C30, which assesses function, symptoms and global health status of cancer patients. All of the scales and single-item measures range in score from 0 to 100 points. A high scale score represents a higher response level. Thus a high score for a functional scale represents a high / healthy level of functioning, a high score for the global health status / QoL represents a high QoL, but a high score for a symptom scale / item represents a high level of symptomatology / problems. Changes will be compared to basal data	6 months and 12 months
Sexual function	Sexual function will be assessed by validated scales according to patient gender. Males: International Index of Erectile Function (or IFE scale) - Score ranges from 5 to 25 points. A higher score corresponds to normal erectile function. Female: Female sexual function Index (or FSFI scale) - Minimal score 2 points. Maximum score 36 points. A higher score corresponds to sexual dysfunction. Changes will be compared to basal data	6 months and 12 months
Urinary function	Urinary incontinence will be assesed by the International Consultation on Incontinence Questionnaire Short Form (or ICIQ-SF). Scale ranges from 0 to 21 points. Any value above 0 points means urinary incontinence. A higher value corresponds to worse urinary incontinence. Changes will be compared to basal data.	6 months and 12 months

Collaborators and Investigators

• Sponsor: Hospital Universitari Vall d'Hebron Research Institute
• Collaborators: Institut d'Investigació Biomèdica de Girona Dr. Josep Trueta; Hospital Universitari de Bellvitge
• Investigators: Principal Investigator: Franco Marinello, MD, PhD, Hospital Universitari Vall d'Hebron

Study record dates

Study Major Dates

• Study Start (Actual): May 25, 2018
• Primary Completion (Actual): February 17, 2021
• Study Completion (Actual): February 17, 2022

Study Registration Dates

• First Submitted: May 25, 2018
• First Submitted That Met QC Criteria: July 14, 2018
• First Posted (Actual): July 26, 2018

Study Record Updates

• Last Update Posted (Actual): March 25, 2022
• Last Update Submitted That Met QC Criteria: March 24, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Disease; Syndrome
• Other Study ID Numbers: SANLARS

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No