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Trial registered on ANZCTR

Registration number

ACTRN12622001207707

Ethics application status

Approved

Date submitted

14/06/2022

Date registered

8/09/2022

Date last updated

21/10/2022

Date data sharing statement initially provided

8/09/2022

Type of registration

Prospectively registered

Titles & IDs

Public title

Assessment of constipation in patients with patients with inflammatory bowel disease using ultrasound

Scientific title

Sonographic Assessment of Constipation in Inflammatory Bowel Disease

Secondary ID [1]

Nil

Universal Trial Number (UTN)

U1111-1278-9972

Trial acronym

Linked study record

Health condition

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

constipation

Inflammatory bowel disease

Functional gastrointestinal disorders

Condition category

Condition code

Oral and Gastrointestinal

Inflammatory bowel disease

Oral and Gastrointestinal

Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

Patients undergoing intestinal ultrasound (IUS) as part of assessment of inflammatory bowel disease and found to have faecal loading will be referred for a single non-contrast low-dose CT scan (LDCT) to confirm the presence of faecal loading. There will not be any follow up LDCT in this study.
The IUS will take approximately 20 minutes and will be performed by either a consultant gastroenterologist with over 7 years of experience with ultrasound or by a fellow currently training in IUS under said gastroenterologist. In cases where the fellow performs the ultrasound, the results will be verified by the supervising gastroenterologist prior to entry into the study. Participants invited to undergo a CT scan will be requested to do so immediately following their IUS clinic appointment (within 4 hours). Adherence will be confirmed by the generation of a LDCT radiology report.

Intervention code [1]

Diagnosis / Prognosis

Comparator / control treatment

Participants with suspected faecal loading will undergo a CT scan to confirm the findings of IUS. The scan will be arranged at a radiology department adjacent to the clinic and patients will be booked into this appointment by study investigators. The CT scan will be performed by a CT technician and the results read by two consultant radiologists who are blinded to one others’ findings. There will only be one CT scan for the entirety of this study.
Confirmation of CT attendance will be confirmed as there will be a report generated to indicate the participant had the scan.
Three days following their LDCT, the results of the scan will be reviewed by one of the investigators. Participants will be contacted and informed of their scan results and if they were found to have faecal loading, they will be asked to consume a sachet of bowel preparation for gentle catharsis (this will be provided to their at the time of first IUS if faecal loading is suspected, and before they leave clinic for the LDCT).
The preparation used will be a single 70g sachet of Glycoprep-C (active ingredient Macrogol 3350, polyethylene glycol) taken orally in a single dose over 1 hour mixed in 250ml of water. Confirmation of ingestion of this is assumed based on agreement to participate in the trial. At the same time of the phone call to confirm taking the sachet, patients will be briefly counselled on standard lifestyle management for constipation and faecal loading including dietary change such as natural fibre, adequate amounts of fluid, exercise, etc. Provision of written information regarding management of constipation will be provided to participants. This is readily available on the Gastroenterology Society of Australia (GESA) website under "patient resources" titled "information about constipation".
Participants will be given the option of attending a follow up IUS to assess response to treatment with bowel preparation. If they elect to participate, they will undergo a second IUS 3 weeks from ingestion of their bowel preparation regimen. No repeat LDCT will be offered.

Control group

Active

Outcomes

Primary outcome [1]

To define and validate intestinal ultrasound (IUS) parameters that identify faecal loading in Inflammatory Bowel Disease (IBD) using low-dose CT (LDCT) as a reference gold standard.

Assessment of agreement between sonographers will be by using a Fleiss kappa coefficient to assess agreement between three readers (two sonographers performing the assessment and a third independent sonographer who will blind read 10-second cine loops of scanned segments).

Assessment of agreement between radiologists for reporting LDCT will be using Cohen's kappa coefficient.

Sonographers will be blinded to one another's reports and radiologists will be blinded to the results of the IUS report at the time of LDCT reporting.

Timepoint [1]

At the time of first ultrasound, patients will undergo a LDCT if they are felt to have faecal loading on IUS (this will occur on the same day as their IUS assessment)

Primary outcome [2]

Sensitivity, specificity, NPV and PPV will be analysed for IUS in diagnosing constipation. The standard this is being assessed against is CT scan which has a reported sensitivity and specificity of 90% and 95% for the diagnosis of constipation.

Timepoint [2]

The above metrics will be calculated at the conclusion of the study following completion of the LDCT and IUS for the last enrolled patient.

Secondary outcome [1]

To prospectively identify rates of proximal constipation and associated symptoms in participants with IBD referred for IUS for evaluation of disease activity in the setting of routine care. Participants with IBD who were referred for IUS, will be invited to fill in an IBS-SSS questionnaire, a validated questionnaire that assesses symptoms of abdominal discomfort. We ask that participants fill in the questionnaire prior to the IUS (in the waiting room) so that their responses to the questionnaire are not influenced by the findings of the IUS.

Timepoint [1]

Participants will be asked to fill in an IBS-SSS questionnaire at baseline (the time of first IUS), between 2-4 weeks post enrolment (at the time of follow up IUS) or 2-4 weeks post enrolment if they elect to take the cathartic but not participate in a follow up IUS.

Secondary outcome [2]

To evaluate clinical response to proactive management of proximal constipation in participants with IBD. Clinical response will be assessed by repeating the IBS-SSS questionnaire that participants filled in at their initial (baseline) visit for IUS

Timepoint [2]

3 weeks post enrolment (following first IUS and LDCT)

Secondary outcome [3]

To evaluate sonographic response to proactive management of proximal constipation in participants with IBD Sonographic response will be assessed by repeating an IUS at a clinic visit.

Timepoint [3]

3 weeks post enrolment (following first IUS and LDCT)

Secondary outcome [4]

To determine the true prevalence of ulcerative colitis associated constipation in the general IBD population

Timepoint [4]

As baseline IUS assessment with validation LDCT

Eligibility

Key inclusion criteria

Formal diagnosis of Inflammatory Bowel Disease (BD)

Minimum age

18 Years

Maximum age

90 Years

Sex

Both males and females

Can healthy volunteers participate?

Key exclusion criteria

o <18 years or >90 years of age
o No formal diagnosis of inflammatory bowel disease
o Participants who are pregnant or breastfeeding
Participants who are unable to provide informed consent
Participants who have undergone prior colonic surgery including restorative ileo-anal pouch anastomosis

Study design

Purpose of the study

Diagnosis

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

Blinded (masking used)

Who is / are masked / blinded?

The people assessing the outcomes

Intervention assignment

Single group

Other design features

Gastroenterologists will be blinded to one others’ IUS findings when performing central reading of IUS
Radiologists will be blinded to one others’ findings on the LDCT report as well as the initial IUS report on faecal loading. The LDCT request form will only ask the question as to whether there is “faecal loading” without any descriptors of what was visualised on IUS.

Phase

Not Applicable

Type of endpoint/s

Efficacy

Statistical methods / analysis

Statistical analysis will be performed with the help of senior statisticians at the Basel Hetzel Institute. Sample size/power calculation. The accuracy of CT scan is upwards of 90% for both sensitivity and specificity. We anticipate the dropout rate to be less than 10% given the design of the trial and previous experience with patient follow-up for IUS assessment in our service. We therefore anticipate a sample size of 70 participants will provide us with an appropriate diagnostic accuracy with a 95% confidence interval.
Inter- and intra-observer variability in reading IUS and LDCT using kappa coefficients
To reduce bias, central reading of IUS data will be performed by an independent investigator via access to secured cine loop files uploaded to REDCap secure storage
Demographic data, blood and stool tests will be evaluated using descriptive statistics.
Evaluation of IUS compared against LDCT in diagnosis of constipation will be done by calculating:
- Sensitivity, specificity
- Positive predictive value and negative predictive value
- Positive and negative likelihood ratios with 95% confidence intervals

Recruitment

Recruitment status

Not yet recruiting

Date of first participant enrolment

Anticipated

1/11/2022

Actual

Date of last participant enrolment

Anticipated

31/07/2023

Actual

Date of last data collection

Anticipated

31/08/2023

Actual

Sample size

Target

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

Recruitment hospital [1]

The Queen Elizabeth Hospital - Woodville

Recruitment postcode(s) [1]

5011 - Woodville

Funding & Sponsors

Funding source category [1]

Government body

Name [1]

The Queen Elizabeth Hospital

Address [1]

The Queen Elizabeth Hospital
28 Woodville Rd
Woodville, South Australia
5011

Country [1]

Australia

Primary sponsor type

Individual

Name

Ryan Mathias

Address

Inflammatory Bowel Disease Service, Level 4B
The Queen Elizabeth Hospital
28 Woodville Road
Woodville South, South Australia
5011

Country

Australia

Secondary sponsor category [1]

Hospital

Name [1]

The Queen Elizabeth Hospital

Address [1]

28 Woodville Road
Woodville South
South Australia 5011

Country [1]

Australia

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Central Adelaide Local Health Network Human Research Ethics Committee

Ethics committee address [1]

Royal Adelaide Hospital
Port Road
Adelaide, SA
5000

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

20/06/2022

Approval date [1]

09/09/2022

Ethics approval number [1]

CALHN HREC 16612

Summary

Brief summary

Inflammatory bowel disease is a chronic and debilitating condition that affects 1 in 250 Australians. As many as 40% of patients with IBD have a concurrent diagnosis of irritable bowel syndrome with either constipation or diarrhoea as a major symptom. Delineating between inflammatory and functional symptoms can make assessment and management difficult in IBD. Concurrent functional symptoms frequentlyresult in unnecessary invasive investigations and even unnecessary escalation in already powerful immunosuppressive therapy. Constipation is the presence of solid or hard stools in the colon that are difficult to pass without significant exertion. They cause stretch, distension and bloating of the bowel which results in pain that can be difficult to differentiate from underlying inflammatory pain in some patients with concurrent IBD.
Ulcerative colitis associated constipation is a phenomenon in which active inflammation results in a slowing of colonic motility and worsening of constipation, predominantly higher up in the colon (proximal constipation). This manifests as pain, bloating and discomfort and not only causes symptoms but can also impact the delivery of medications to the colon that rely on normal colonic movements. 
Intestinal ultrasound (IUS) has been used successfully across many countries to accurately and safely assess inflammatory bowel disease and allow for real-time decision making as a point of care test. It has been shown in small studies to be able to identify colonic contents such as solid or liquid stool, but this has not been formally defined. The ability of IUS to accurately distinguish between proximal faecal loading versus inflammatory pathology would allow a more safe, cost-effective and tailored approach to managing patients in real-time. 
Hypotheses: 
1. IUS accurately and objectively measures proximal constipation in IBD as validated against CT as the reference standard
2. Unrecognised and frequent proximal constipation is a common cause for symptoms in participants with IBD
3. Proactive management of proximal constipation in IBD leads to an improvement in clinical symptoms and IUS parameters

Trial website

Trial related presentations / publications

Public notes

Contacts

Principal investigator

Name

Dr Ryan Mathias

Address

Inflammatory Bowel Disease Service
Level 4C
The Queen Elizabeth Hospital
28 Woodville Road
Woodville South, South Australia
5011

Country

Australia

Phone

+61 8 82228984

Fax

ryan.mathias@sa.gov.au

Contact person for public queries

Name

Ryan Mathias

Address

Inflammatory Bowel Disease Service Level 4C
The Queen Elizabeth Hospital
28 Woodville Road
Woodville South, South Australia
5011

Country

Australia

Phone

+61 8 82228984

Fax

ryan.mathias@sa.gov.au

Contact person for scientific queries

Name

Ryan Mathias

Address

Inflammatory Bowel Disease Service
Level 4C
The Queen Elizabeth Hospital
28 Woodville Road
Woodville South, South Australia
5011

Country

Australia

Phone

+61 8 82228984

Fax

ryan.mathias@sa.gov.au

Data sharing statement

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

Yes

What data in particular will be shared?

De-identified data underlying published results

When will data be available (start and end dates)?

Available from December 2023 - December 2028

Available to whom?

Researchers who provide a methodologically sound proposal

Available for what types of analyses?

Meta-analysis
Systematic reviews

How or where can data be obtained?

Contact the principal investigator via email ryan.mathias@sa.gov.au and subject to approval by principal investigator.

What supporting documents are/will be available?

Doc. No.	Type	Citation	Link	Email	Other Details	Attachment
16371	Study protocol			ryan.mathias@sa.gov.au
16401	Ethical approval			ryan.mathias@sa.gov.au	Ethics approval obtained

Results publications and other study-related documents

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