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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] 307914 0
Nil
Universal Trial Number (UTN)
U1111-1278-9972
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
constipation 326584 0
Inflammatory bowel disease 326585 0
Functional gastrointestinal disorders 327560 0
Condition category
Condition code
Oral and Gastrointestinal 323827 323827 0 0
Inflammatory bowel disease
Oral and Gastrointestinal 323828 323828 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
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] 323743 0
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] 331669 0
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] 331669 0
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] 332497 0
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] 332497 0
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] 410699 0
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] 410699 0
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] 410700 0
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] 410700 0
3 weeks post enrolment (following first IUS and LDCT)
Secondary outcome [3] 410889 0
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] 410889 0
3 weeks post enrolment (following first IUS and LDCT)
Secondary outcome [4] 414993 0
To determine the true prevalence of ulcerative colitis associated constipation in the general IBD population
Timepoint [4] 414993 0
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?
No
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
70
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 22526 0
The Queen Elizabeth Hospital - Woodville
Recruitment postcode(s) [1] 37765 0
5011 - Woodville

Funding & Sponsors
Funding source category [1] 311590 0
Government body
Name [1] 311590 0
The Queen Elizabeth Hospital
Country [1] 311590 0
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] 313029 0
Hospital
Name [1] 313029 0
The Queen Elizabeth Hospital
Address [1] 313029 0
28 Woodville Road
Woodville South
South Australia 5011
Country [1] 313029 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 311038 0
Central Adelaide Local Health Network Human Research Ethics Committee
Ethics committee address [1] 311038 0
Royal Adelaide Hospital
Port Road
Adelaide, SA
5000
Ethics committee country [1] 311038 0
Australia
Date submitted for ethics approval [1] 311038 0
20/06/2022
Approval date [1] 311038 0
09/09/2022
Ethics approval number [1] 311038 0
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 119778 0
Dr Ryan Mathias
Address 119778 0
Inflammatory Bowel Disease Service
Level 4C
The Queen Elizabeth Hospital
28 Woodville Road
Woodville South, South Australia
5011
Country 119778 0
Australia
Phone 119778 0
+61 8 82228984
Fax 119778 0
Email 119778 0
[email protected]
Contact person for public queries
Name 119779 0
Ryan Mathias
Address 119779 0
Inflammatory Bowel Disease Service Level 4C
The Queen Elizabeth Hospital
28 Woodville Road
Woodville South, South Australia
5011
Country 119779 0
Australia
Phone 119779 0
+61 8 82228984
Fax 119779 0
Email 119779 0
[email protected]
Contact person for scientific queries
Name 119780 0
Ryan Mathias
Address 119780 0
Inflammatory Bowel Disease Service
Level 4C
The Queen Elizabeth Hospital
28 Woodville Road
Woodville South, South Australia
5011
Country 119780 0
Australia
Phone 119780 0
+61 8 82228984
Fax 119780 0
Email 119780 0
[email protected]

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 [email protected] and subject to approval by principal investigator.


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
16371Study protocol  [email protected]
16401Ethical approval  [email protected] Ethics approval obtained



Results publications and other study-related documents

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