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Trial registered on ANZCTR

Registration number

ACTRN12616000334404

Ethics application status

Approved

Date submitted

10/03/2016

Date registered

15/03/2016

Date last updated

29/01/2019

Date data sharing statement initially provided

29/01/2019

Type of registration

Prospectively registered

Titles & IDs

Public title

Determining normal anorectal physiology values in healthy females.

Scientific title

Determining normal anorectal physiology values in healthy females.

Secondary ID [1]

None

Universal Trial Number (UTN)

Trial acronym

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Anorectal physiology in healthy subjects

Condition category

Condition code

Oral and Gastrointestinal

Normal oral and gastrointestinal development and function

Intervention/exposure

Study type

Observational

Patient registry

False

Target follow-up duration

Target follow-up type

Description of intervention(s) / exposure

All eligible volunteers will be invited for a one hour, single visit, anorectal physiology testing. No follow up is planned.
.
After obtaining informed consent, patients will perform anorectal manometry (ARM) and balloon expulsion testing (BET) according to a standard protocol. Briefly, after rectal examination, a 7-lumen water-perfused manometry catheter with 0.5 cm spaced sideholes and a compliant balloon attached to the end is used (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, cough pressure and duration of maximum anal squeeze and (iii) rectal pressure on strain and concomitant anal relaxation or paradoxical contraction. Neurophysiology testing using surface EMG is used to asses for squeeze and anal relaxation on strain. This takes approximately 15 minutes.

Sensation thresholds will be tested using two different techniques:
1- Using a 50ml syringe air continuously injected at a rate of 100ml/minute into a balloon at the end of an anorectal catheter, as is standard in the Unit
2- Using an infinitely compliant balloon continuously injected in a rapid barostat protocol, as recently been suggested to be a more reliable measure of sensation

All patients will perform both techniques. In both techniques:
a. The patient is told to report when they first feel the sensation of the balloon inside the rectum, which is recorded as the rectal sensitivity threshold.
b. Continuing to fill the balloon with air the patient then reports when they have the urge to defecate.
c. Still continuing to fill the balloon with air the patient then reports when they cannot tolerate the inflation of the balloon any more, which is recorded as the maximum tolerated volume.

The balloon is quickly deflated (manually or automatically) at the time of reported maximal tolerated volume or at a maximum volume of 300 ml, whatever is reached sooner. Sensation testing will takes approximately 25 minutes.

Dyssynergic defecation using the balloon expulsion test will be tested using three different techniques:
1- Using a 50 ml water filled party balloon tied to a catheter, as is standard protocol in the Unit
2- Using a 16F Foley catheter filled with 50 ml water as has been recently suggested
3- Using a commercially available non-latex rectal balloon.

All patients will perform these techniques, while the order of performance will be equally distributed. In both techniques:
a. The patients try to push the balloon out while sitting over a private toilet.
b. The time it takes to expel the balloon is noted. If the patient is unable to expel balloon after 3 minutes the balloon is deflated and removed.
This will take approximately 10 minutes.

Anorectal ultrasound will be performed as standard to ensure no major breaks in the internal or external sphincter that may undermine the normal exam. This involves 10 minutes of testing.

Intervention code [1]

Diagnosis / Prognosis

Comparator / control treatment

No control group

Control group

Uncontrolled

Outcomes

Primary outcome [1]

For the primary outcome of determining the normal range of values of anorectal sensorimotor physiological testing in healthy volunteers, the outcome measures are the results of the test performed. These include mean (+-SD) of anal resting pressure, anal pressure on squeeze, anal squeeze duration, rectal pressure on strain, anal relaxation on strain, sensory thresholds and balloon expulsion time.

Timepoint [1]

end of study procedure

Secondary outcome [1]

For the secondary outcome of determining the best method of measuring rectal sensitivity, the outcome measure will be the correlation between elastic balloon measurements and the barostat measurements of rectal sensitivity.

Timepoint [1]

end of study procedure

Secondary outcome [2]

For the optimum method of diagnosing dyssenergic defecation using balloon expulsion time, the outcome measure will be time taken to evacuate the different balloons using the three methods described above.

Timepoint [2]

end of study procedure

Eligibility

Key inclusion criteria

Inclusion criteria include:
1- Age between 20 and 75
2- Females
3- English speakers
4- Willingness to answer screening questionnaire
5- Willingness to give written informed consent
6- Willingness to comply with the study.

Minimum age

20 Years

Maximum age

75 Years

Sex

Females

Can healthy volunteers participate?

Yes

Key exclusion criteria

All volunteers will be requested to answer a screening questionnaire. This will not be reimbursed.

Exclusion criteria include:
1. Women lactating or pregnant
2. Definable gastrointestinal disorder based on the ROME questionnaire componenet of the screening questionnaire. .
3. Presence of overt organic anorectal disorder
4. Medications that alter motility of the GI tract such as loperamide.
5. History of anorectal or distal colon surgery.
6. History of complicated delivery
7. Previous anorectal physiological testing.
8. 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. Psychological illness or condition will be assessed by: (1) HAD, (2) screening questionnaire questions about medical conditions, current medications, and (3) brief physician interview and discussion of PISCF before patients consent

Study design

Purpose

Screening

Duration

Cross-sectional

Selection

Convenience sample

Timing

Prospective

Statistical methods / analysis

For the primary aim, there is no hypothesis to test so statistical power considerations do not apply. A sufficiently large sample is however needed to estimate the standard deviation accurately. A sample size >30 is typically considered large enough for small random sampling variations to be smoothed out and a sample size of 40 is proposed.

For the secondary aims of sensory testing, the smallest clinically relevant correlation between measurements obtained by the two methods is defined as 0.5 (Pearson correlation). To achieve statistical power 0.8 at the 0.01 level of statistical significance requires n=40 individuals.
For the secondary aim of dyssynergic defecation, sample size requirements for a dichotomous measure are typically larger than for quantitative measures. For a difference between discordant pair probabilities of 0.2, n=120 patients are required to achieve statistical power 0.8 at the 0.05 level of statistical significance. We are aware that this may not be achievable in this study but this being a secondary aim we deem this reasonable.

Normal range determination will employ Normal theory to estimate the range of values either side of the sample mean within which 95% of individuals are expected to fall. If the measure follows an approximately Normal distribution this is known to be +- 2 standard deviations either side of the sample mean (more precisely -1.96 < z < +1.96 on a Unit Normal scale). If the measure’s distribution is substantially non-Normal the measure will first be transformed to an approximately Normal distribution, normal range boundaries established then those boundaries back-transformed to the original scale. In the case of a log-transformed measure this would be similar to the geometric mean.

For the secondary aim of sensory testing, measurements taken by the two procedures considered are hypothesized to be highly proportional rather than to agree numerically. Statistical analysis will therefore focus on correlations between measurements taken by the two methods.
For the secondary aim of defining dyssnergic defecation, concordance of diagnosis according to the two methods will be assessed using McNemar’s test and described using the Kappa coefficient of concordance

Recruitment

Recruitment status

Recruiting

Date of first participant enrolment

Anticipated

1/04/2016

Actual

1/11/2016

Date of last participant enrolment

Anticipated

31/12/2019

Actual

Date of last data collection

Anticipated

31/12/2019

Actual

Sample size

Target

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

NSW

Recruitment hospital [1]

Royal North Shore Hospital - St Leonards

Recruitment postcode(s) [1]

2065 - St Leonards

Funding & Sponsors

Funding source category [1]

Hospital

Name [1]

Royal North Shore Hospital (Public)

Address [1]

Royal North Shore Hospital
Gastroenterology Department
Reserve Road
St Leonards, NSW 2065

Country [1]

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]

None

Name [1]

None

Address [1]

None

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Northern Sydney Local Health District HREC

Ethics committee address [1]

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

15/01/2016

Approval date [1]

08/02/2016

Ethics approval number [1]

NSLHD reference RESP/15/347

Summary

Brief summary

Constipation and faecal incontinence (FI) are major health problems associated with significant personal and economic burden. First line treatment for these disorders is conservative and includes dietary modification and medication. If these fail, current guidelines recommend assessing physiological abnormalities by anorectal manometry (ARM) and balloon expulsion testing (BET). The results of these are then used to guide further management of the patients, including biofeedback therapy, neuromodulation and surgical interventions.
Given the central role of ARM, a relative surprisingly lack of standardization is apparent in the literature. Factors such as catheter type, study protocol and analysis of results vary widely. With regards to FI, a wide range of values is reported as ‘normal’ for anal sphincter function, and experts recommend that each unit have their own range of values for defining abnormalities. For patients with constipation, ARM and BET are required for diagnosing dyssenrgic defecation, which has been shown to be a strong predictor of biofeedback success. Nevertheless, making this diagnosis, which includes evidence of an uncoordinated defection manoeuvre, is controversial at best, with conflicting data on the specifics of the procedure and diagnosis. 
The sensory component of the defecation process is also slowly being elucidated. Whereas patients with constipation may display rectal hyposensitivity, patients with FI may display either hypo or hyper sensitivity. This may have implications for the treatment of these disorders, as anorectal biofeedback can be used to teach patients how to modulate their sensory thresholds, leading to improved outcomes.  Notwithstanding, how best to assess for these rectal sensory abnormalities, and what are the normal cut-offs that should be used, is still unclear. 
We thus aim to describe the normal sensorimotor physiology as assessed by ARM in healthy volunteers. Specifically, we aim to (1) establish normal range of values for our specific equipment and protocol and (2) evaluate comparative methods for assessing sensorimotor function. These results will be used to enhance our ability to define normal and abnormal defecatory physiology and help treat future patients with these distressing chronic conditions.

Trial website

Trial related presentations / publications

Public notes

Study Ad:

Normal Volunteers Needed
We are conducting a study on normal bowel function. 
The study involves one hour of testing. 
Females aged between 20 and 75 years are required.
If you are in good general health, without symptoms, are not pregnant or breastfeeding, and are interested in participating, please contact the following number 02 94632460 
You will be reimbursed for your time.

Contacts

Principal investigator

Name

Dr Allison Malcolm

Address

Gastroenterology Department
Royal North Shore Hospital,
Reserve Road
St Leonards, NSW 2065

Country

Australia

Phone

+61296432450

Fax

+61294632041

[email protected]

Contact person for public queries

Name

Allison Malcom

Address

Gastroenterology Department
Royal North Shore Hospital,
Reserve Road
St Leonards, NSW 2065

Country

Australia

Phone

+61296432450

Fax

+61294632041

[email protected]

Contact person for scientific queries

Name

Yoav Mazor

Address

Gastroenterology Department
Royal North Shore Hospital,
Reserve Road
St Leonards, NSW 2065

Country

Australia

Phone

+61294632460

Fax

+61294632041

[email protected]

Data sharing statement

Will individual participant data (IPD) for this trial be available (including data dictionaries)?

No/undecided IPD sharing reason/comment

As per ethics, only investigators will have access to patient data. Furthermore, the coding used in our raw data is specific to our unit and will unable to be interpreted by others.

What supporting documents are/will be available?

No Supporting Document Provided

Results publications and other study-related documents

Documents added manually

No documents have been uploaded by study researchers.

Documents added automatically

Source	Title	Year of Publication	DOI
Embase	Anorectal physiology in health: A randomized trial to determine the optimum catheter for the balloon expulsion test.	2019	https://dx.doi.org/10.1111/nmo.13552

N.B. These documents automatically identified may not have been verified by the study sponsor.

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