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Trial registered on ANZCTR


Registration number
ACTRN12616000056493
Ethics application status
Approved
Date submitted
13/01/2016
Date registered
20/01/2016
Date last updated
19/02/2019
Date data sharing statement initially provided
19/02/2019
Date results information initially provided
19/02/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Percutaneous posterior tibial nerve stimulation (PTNS) and biofeedback for treating faecal incontinence
Scientific title
Percutaneous posterior tibial nerve stimulation (PTNS) for treating faecal incontinence in females: A pilot study of combination treatment with biofeedback.

Secondary ID [1] 288301 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Faecal Incontinence 297262 0
Condition category
Condition code
Oral and Gastrointestinal 297464 297464 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
All patients with faecal incontinence (FI) referred to the Neurogastroenterology Unit at Royal North Shore for biofeedback treatment will be screened using physiological testing and symptom based questionnaires as routinely used in the Unit. These include on initial evaluation a general symptom questionnaire (Anorectal Manometry Questionnaire), the Rome III Integrative Questionnaire, and the Hospital Anxiety and Depression (HAD) scale. After digital rectal examination, patients undergo comprehensive anorectal function studies, which include using a 7-lumen water-perfused manometry catheter with 0.5 cm spaced sideholes and a compliant balloon attached to the end (Dentsleeve International, Canada). The catheter is connected to calibrated pressure transducers and data from the pressure transducers is displayed in digital form on a computer using data conversion software (Neomedix, Sydney Australia). Each individual study comprises assessments of the following parameters: (i) resting anal sphincter pressure, (ii) maximum anal sphincter squeeze pressure and duration of maximum anal squeeze pressure, (iii) straining rectal pressure and concomitant anal relaxation or paradoxical contraction, (iv) rectal sensitivity thresholds using a latex balloon and/or barostat studies and (v) balloon expulsion test (time taken to expel a rectal balloon inflated with 50 ml of warm water whilst the patient is seated on a private toilet).
If clinically indicated, further testing including anorectal ultrasound, defacting proctogram and/or colonoscopy will be performed to rule out a structural/ organic cause for the patients’ symptoms.
For the current study, patients will be screened for eligibility criteria as detailed below. Patients who satisfy these criteria will be given oral and written explanation detailing the PTNS procedure and trial, and offered participation in the study.
All patients will go on to receive standard of care anorectal BF training. This consists of 30-60 minute sessions, every week for six weeks, with a gastroenterologist and/or nurse specialist. The protocol consists of (1) education regarding the anatomy of normal defecation, (2) advice on correct toilet positioning, (3) anal squeeze pressure exercises, aimed at improving strength and duration of squeeze, (4) diaphragmatic breathing, with manometric feedback, to achieve adequate rectal pressure, (5) manometry-based biofeedback to allow anal relaxation to be synchronized with strain, (6) balloon expulsion retraining, and (7) rectal sensory retraining when appropriate.
A disease specific questionnaire (Faecal Incontinence Questionnaire) is filled out before BF. Both before and after BF treatment all patients fill out the Faecal Incontinence Severity Index (FISI), the quality of life questionnaire (SF36) and a 10 cm visual analogue scale (VAS) for (i) global bowel satisfaction (score anchors: 0 = completely unsatisfied; 10 = completely satisfied), (ii) impact of bowel dysfunction on quality of life (score anchors: 0 = no impact; 10 = most impact) and (iii) willingness to participate in the therapeutic course (score anchors: 0 = not willing; 10 = very willing).
In addition to this standard of care BF treatment, patients consenting to participate in the study will undergo five sessions of BF and PTNS at the same time. The patients will undergo these combined sessions once weekly for 5 weeks, and then will go on to receive 7 additional weekly sessions of PTNS only. Another combined BF and PTNS session will be performed at 3 months, for a total of 13 PTNS sessions. Thus, all patients included in the study will be given the benefit of both BF treatment and PTNS neurostimulation. A combined session of PTNS and BF includes 30 minutes of PTNS and afterwards performing BF exercises.
PTNS involves a needle electrode being inserted adjunct to the posterior tibial nerve at the medial malleolus of the ankle. It is inserted about 3–4 centimetres. The electrode is then connected to a hand held nerve stimulator which sends an electrical impulse to the nerve. This nerve impulse is transmitted to the sacral plexus which regulates the control of bladder and pelvic floor muscles. The maximum treatment intensity is determined in the following way: the stimulus intensity is increased slowly until the patient's great toe begins to curl. The level at which the patient's toe curls is determined to be the maximum intensity for treatment. Each treatment session lasts 30 minutes of continuous stimulation.
PTNS therapy will be delivered using the incontinence-control electrical stimulation system, non-implantable (Endotherapeutics Pty Ltd). This device is listed on the ARTG and will be used for the indication approved under this listing. PTNS will be delivered by a qualified nurse who has undergone specific training in PTNS treatment and follow-up.
Intervention code [1] 293598 0
Treatment: Devices
Comparator / control treatment
Treatment groups will be compared to historical controls. No active controls are planned for this study.
Historical controls have received treatment by BF only, as standard protocol, including 6 weekly visits and a 3 months follow up. They will be selected from an internal archive consisting of patients who have been treated between 1/1/2008 and 31/12/2014. The analysis of these patients data has been authorised by NSLHD HREC ethics committee on the 15/10/2014, reference LNR/14/HAWKE/372, titled 'Evaluation of Anorectal Biofeedback for the Management of Faecal Incontinence'. As all analysis of this data is retrospective, this study has not been registered on a public registery.
Control group
Historical

Outcomes
Primary outcome [1] 297027 0
Primary outcome for assessing feasability will be the completion rate of the program, as defined by at least 80% attendance of treatment sessions and attending the end of treatment assessment by a physician.
Timepoint [1] 297027 0
3 and 6 months from start of treatment
Primary outcome [2] 297108 0
Primary outcome measure for assessing the impact of PTNS treatment on anorectal physiology will be the change in anorectal manometry (ARM) measurements before and after PTNS treatment.
Timepoint [2] 297108 0
Anorectal manometry (ARM) will be performed on the screening visit, at visits at 2,5 and 9 weeks, and on the final visit week 13. On each of the visits, ARM will be performed before and after PTNS treatment.
Primary outcome [3] 297109 0
To assess the efficacy of combination therapy of PTNS and BF for FI. This will be primarly assessed by the reduction in severity of faecal incontinence (FISI and stool diaries).
Timepoint [3] 297109 0
3 and 6 months from start of treatment
Secondary outcome [1] 319879 0
Secondary outcome measures for assessing treatment efficacy will include change in quality of life (as assessed by SF36 and VAS for impact of bowel dysfunction on quality of life, control over bowel motions and satisfaction with bowel motions).
Timepoint [1] 319879 0
On visit 1 VAS, SF-36, FISI and Faecal incontinence questionnaires.
On visit 6 VAS questionnaire and FISI.
On the final study visit VAS questionnaire, FISI and SF-36 questionnaire will be filled out again.

Eligibility
Key inclusion criteria
Patients who are referred to biofeedback treatment for faecal incontinence and satisfy the following will be offered participation:
1. Females
2. Age >=18 and =<80
3. Faecal incontinence: defined as an uncontrolled passage of faecal material occurring at least 2-4 times a month, in the last 6 months.
4. Urge symptoms: defined as having an urge sensation before the uncontrolled passage in at least part of the FI episodes.
5. Failure of a trial of diet and bulking or laxative therapy in an effort to restore normal bowel movements.
6. Severity of FI: a minimal score of 8 on the FIS.
7. Willingness to give written informed consent and willingness to comply with the study.
Minimum age
18 Years
Maximum age
80 Years
Gender
Females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Presence of overt organic anorectal disorder - based on standard testing including physician assessment and imaging (anorectal ultrasound and/or colonoscopy).
2. Any general medical condition or medication that may compromise PTNS/BF treatment including:

a. Hypercoagulability state or anti-coagulation medication.
b. Latex allergy.
c. Implanted stimulator, pacemaker or defibrillator
d. Sciatica symptoms
e. Peripheral neuropathy
f. Peripheral vascular disease

3. Patients with a history of psychological illness or condition such as to interfere with the patient’s ability to understand the requirements of the study.
4. Women lactating, pregnant or of childbearing potential who are not willing to avoid pregnancy during the study
5. Previous anorectal biofeedback training.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Not Applicable
Type of endpoint(s)
Efficacy
Statistical methods / analysis
Quantitative measures of improvement and overall success rates of combination therapy will be compared to a similar 1:1 matched group of historical controls. Although this is a feasibility pilot study, we calculated a difference between groups corresponding to a Cohen’s d of 1.0 requires n=12 per group available for statistical analysis to achieve power=0.8 at the 0.05 (two-tailed) level of statistical significance based on the Wilcoxon Signed Ranks test assuming minimum asymptotic relative efficiency.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 5029 0
Royal North Shore Hospital - St Leonards
Recruitment postcode(s) [1] 12515 0
2065 - Royal North Shore Hospital

Funding & Sponsors
Funding source category [1] 292677 0
Hospital
Name [1] 292677 0
Research Trust Fund from Royal North Shore Hospital
Address [1] 292677 0
Royal North Shore Hospital,
Reserve Road
St Leonards, NSW 2065
Country [1] 292677 0
Australia
Funding source category [2] 295624 0
Charities/Societies/Foundations
Name [2] 295624 0
Colorectal Surgical Society of Australia and New Zealand
Address [2] 295624 0
Suite 6
9 Church St
Hawthorn VIC 3122
Country [2] 295624 0
Australia
Primary sponsor type
Government body
Name
Northern Sydney Local Health District
Address
Royal North Shore Hospital,
Reserve Road
St Leonards, NSW 2065
Country
Australia
Secondary sponsor category [1] 291397 0
None
Name [1] 291397 0
None
Address [1] 291397 0
None
Country [1] 291397 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 294146 0
Northern Sydney Local Health District HREC
Ethics committee address [1] 294146 0
Ethics committee country [1] 294146 0
Australia
Date submitted for ethics approval [1] 294146 0
09/11/2015
Approval date [1] 294146 0
18/11/2015
Ethics approval number [1] 294146 0
RESP/15/309

Summary
Brief summary
Faecal incontinence (FI) is a chronic, debilitating condition with enormous consequences for patients and the community. Numerous studies have documented the tremendous negative impact of FI on quality of life. FI has also been shown to be associated with substantial economic costs for the local health system.

Since FI is believed to be a heterogeneous disorder, initial management is symptom based. Addressing the underlying abnormal bowel habits, if present, is the first step. Additional conservative therapies include dietary, medical and psychological modifications, and are estimated to benefit a quarter of patients. When a conservative approach fails, treatment with biofeedback (BF) is often recommended. A multitude of perspective and randomized trials have persistently shown short and long-term improvement in around 60% to 70% of patients treated with BF.

Neuromodulation is an established therapeutic modality in the treatment of patients suffering from different pelvic floor disorders. For patients with FI failing BF, the only well-established option at present is neuromodulation by an implantable sacral nerve stimulator. This treatment is invasive and costly, has potential significant complications and is associated with significant financial burden for the local health system. Therefore, there is a need for a less invasive and costly method of performing neuromodulation.

Percutaneous tibial nerve stimulation (PTNS) has the potential to address these disadvantages. With this method, neuromodulation is delivered through the posterior tibial nerve using a disposable needle electrode. Although PTNS is a well-proven and recognized treatment for urge urinary incontinence, in the last decade its role in treating patients with FI is slowly being elucidated. A recent systemic review included 6 prospective studies of PTNS for treating FI, and showed that PTNS results in significant improvements in some outcome measures of these patients. In all of these studies, patients were required to fail conservative management, but not specifically biofeedback, and in none of the studies was PTNS evaluated in combination with BF.

We thus hypothesize that the combination of PTNS and BF for treating patients with FI, especially patients with urge incontinence, who are at high risk for BF failure, will be more effective than the current standard of care of BF treatment only. The impact of this combined efficacy will translate into improving the care of our patients, reducing the negative impact on the patients and their families’ quality of life, and reducing the costs for our local health system.

Our main study objective is to determine the feasibility of combining PTNS with BF for the treatment of patients with faecal incontinence. Our secondary objectives are (1) To determine the physiological effect of combination therapy of PTNS and BF on anorectal dysfunction and (2) To assess the efficacy of combination therapy of PTNS and BF for FI.

Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 62690 0
Dr Allison Malcolm
Address 62690 0
Gastroenterology Department
Royal North Shore Hospital,
Reserve Road
St Leonards, NSW 2065
Country 62690 0
Australia
Phone 62690 0
+61299660057
Fax 62690 0
Email 62690 0
amalcolm@med.usyd.edu.au
Contact person for public queries
Name 62691 0
Dr Yoav Mazor
Address 62691 0
Gastroenterology Department
Royal North Shore Hospital,
Reserve Road
St Leonards, NSW 2065
Country 62691 0
Australia
Phone 62691 0
+61294632460
Fax 62691 0
Email 62691 0
yoavmazor@gmail.com
Contact person for scientific queries
Name 62692 0
Dr Yoav Mazor
Address 62692 0
Gastroenterology Department
Royal North Shore Hospital,
Reserve Road
St Leonards, NSW 2065
Country 62692 0
Australia
Phone 62692 0
+61294632460
Fax 62692 0
Email 62692 0
yoavmazor@gmail.com

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Not needed.
What supporting documents are/will be available?
No other documents available
Summary results
Have study results been published in a peer-reviewed journal?
No
Other publications
Have study results been made publicly available in another format?
Yes
Other publication details
Citation type [1] 1287 0
Conference abstract
Citation/DOI/link/details [1] 1287 0
Digestive Disease Week - International Gastroenterology Conference, May 2018.
Results – plain English summary
This study shows that combining PTNS with biofeedback for the treatment of faecal incontinence in women is feasible, safe and well accepted by both patients and nurses. As this was a pilot study, conclusions regarding efficacy await larger studies.