ANZCTR - Registration

Please note the ANZCTR will be unattended from Friday 20 December 2024 for the holidays. The Registry will re-open on Tuesday 7 January 2025. Submissions and updates will not be processed during that time.

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Trial registered on ANZCTR

Registration number

ACTRN12617001146381p

Ethics application status

Not yet submitted

Date submitted

22/07/2017

Date registered

7/08/2017

Date last updated

7/08/2017

Type of registration

Prospectively registered

Titles & IDs

Public title

Effect of Vancomycin and Infliximab on clinical parameters and mucosal healing in children with Primary Sclerosing Cholangitis (PSC)- Ulcerative Colitis (UC) or moderate to severe UC

Scientific title

Use of Vancomycin in Primary Sclerosing Cholangitis (PSC)-Ulcerative Colitis (UC) and use of Biologics in moderate to severe UC: Comparison of clinical parameters, mucosal healing, biomarkers, faecal microbiome and genotype between responders and non-responders.

Secondary ID [1]

Nil known

Universal Trial Number (UTN)

Trial acronym

Linked study record

Health condition

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

Ulcerative Colitis

Primary Sclerosing Cholangitis

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

Observational

Patient registry

False

Target follow-up duration

Target follow-up type

Description of intervention(s) / exposure

This is an observation of clinical practice and determination of key alterations in immunomodulation, biomarkers and and gut microflora between those responding and not responding to Vancomycin and Infliximab with UC.

Patients with moderate to severe Ulcerative Colitis will be exposed to the drug Infliximab and patients with primary sclerosing cholangitis- ulcerative colitis will be exposed the antibiotic vancomycin. The duration of this observation period will be 5 years.
The treatment received by participants is as per standard of care and is not affected by enrolment in this study. Patients would receive the same treatment with or without the presence of the study.

Intervention code [1]

Not applicable

Comparator / control treatment

No control group

Control group

Uncontrolled

Outcomes

Primary outcome [1]

At inital enrollment and 3 months later we will systematically assess; mucosal healing, which will be assessed by colon biopsy sample analysis.

Timepoint [1]

3 months

Secondary outcome [1]

Identify the changes in mucosal cytokine T regulatory profile which will be assessed from mucosal samples.

Timepoint [1]

3 months

Secondary outcome [2]

Faecal microbiome by performing stool sample analysis

Timepoint [2]

5 years

Secondary outcome [3]

Mucosal microbiome by performing mucosal tissue analysis

Timepoint [3]

5 years

Secondary outcome [4]

Assessment of clinical response to treatment with faecal calprotectin (stool sample) and C reactive protein (blood sample)

Timepoint [4]

5 years

Secondary outcome [5]

Response of PSC to treatment by reviewing imaging such as MRCP (Magnetic resonance cholangiopancreatography)

Timepoint [5]

5 years

Eligibility

Key inclusion criteria

Children must have either of the following conditions:
Paediatric Primary Sclerosing Cholangitis- Ulcerative Colitis and are to be treated with Vancomycin
Paediatric Moderate Severe- Ulcerative Colitis and are to be treated with Infliximab

Minimum age

6 Years

Maximum age

18 Years

Sex

Both males and females

Can healthy volunteers participate?

Key exclusion criteria

Children who are not requiring treatment for primary sclerosing cholangitis- ulcerative colitis with vancomycin and moderate to severe ulcerative colitis with biologics will be excluded from the trial

Study design

Purpose

Natural history

Duration

Longitudinal

Selection

Defined population

Timing

Prospective

Statistical methods / analysis

Recruitment

Recruitment status

Not yet recruiting

Date of first participant enrolment

Anticipated

31/08/2017

Actual

Date of last participant enrolment

Anticipated

30/12/2022

Actual

Date of last data collection

Anticipated

Actual

Sample size

Target

100

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

QLD

Funding & Sponsors

Funding source category [1]

Self funded/Unfunded

Name [1]

Nil funding

Address [1]

Nil

Country [1]

Primary sponsor type

Individual

Name

Associate Professor Peter Lewindon

Address

Lady Cilento Children's Hospital, 501 Stanley st, South Brisbane, Queensland, 4101

Country

Australia

Secondary sponsor category [1]

None

Name [1]

Nil

Address [1]

Nil

Country [1]

Ethics approval

Ethics application status

Not yet submitted

Ethics committee name [1]

Children's Health Queensland Ethics Committee

Ethics committee address [1]

Lady Cilento Children's Hospital, 501 Stanley St, South Brisbane, Queensland, 4101

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

31/08/2017

Approval date [1]

Ethics approval number [1]

Summary

Brief summary

UC is a destructive chronic inflammatory disorder of the gastrointestinal tract. Children have a 30 to 40% colectomy rate at 10 years (1). Paediatric onset UC accounts for 15 to 20% of all UC patients (1). Disease is extensive, pancolitis in 60-80% of children occurs twice as frequent as in adults (1). 

Currently, the pathogenesis of UC is unknown. It is thought that a complex dysregulated immune response to gut microflora plays a major role.  Different phenotypes of UC appear to respond to different medical therapies.  In particular, two phenotypes, that of moderate-severe UC and PSC-UC, have demonstrated response to newer "biologic agents" like anti-Tumour Necrosis Factor-alpha antibodies and oral vancomycin respectively.

Biologics are considered for children with Acute severe presentations not responding to steroids and for chronic refractory UC, uncontrolled by aminosalicylates and thiopurines(1). Indeed, 5-10% of patients with UC require acute surgical intervention because of fulminant colitis refractory to medical therapy (1).

Similarly, Antibiotics have gained interest in the management of Colitis, and in  small study reported by our group, Vancomycin has shown significant improvement, even complete mucosal healing of the colitis associated with Primary Sclerosing Cholangitis, PSC-UC.  There has also been improvement in blood tests of liver inflammation although the significance of these liver improvements remain to be determined.(2). PSC in conjunction with UC, whilst associated with milder bowel disease can lead to to liver cirrhosis, colorectal cancer and cholangiocarcinoma (1. However, these two therapies are new and the mechanisms and impact on mucosal healing and regain of liver function is not yet quantified.

We propose to study these evolving treatment modalities in an open label study of patients with UC, including those with PSC-UC who are failing conventional therapies (5-ASA and/or immunosuppression). Children with UC considered for biologics and children with PSC-UC and considering oral Vancomycin will be considered for this study. Consistent with our current clinical practice, at initial enrolment and after 3 months therapy we will systematically assess: patients clinical characteristics, inflammatory markers (CRP, fecal calprotectin), mucosal healing by endoscopy and colonoscopy and features of PSC on Magnetic Resonance Cholangio Pancteatography (MRCP) in those with PSC-UC.

We will also collect an additional 10 biopsies at each colonoscopy, each 1-2mm (consistent with our other Ethically approved biopsy study in Crohn's Disease with no additional risk) to assess activity of populations of white blood cells and microflora.  Under GA, blood will be obtained to assess IBD genetic mutations.  Stool for microbiome will be collected at same time as for faecal calprotectin, a clinical disease marker.

Trial website

Trial related presentations / publications

Public notes

Contacts

Principal investigator

Name

A/Prof Peter Lewindon

Address

Lady Cilento Children's Hospital, 501 Stanley St, South Brisbane, Queensland, 4101

Country

Australia

Phone

+61 7 3068 8111

Fax

p.lewindon@uq.edu.au

Contact person for public queries

Name

Harveen Singh

Address

Lady Cilento Children's Hospital, 501 Stanley St, South Brisbane, Queensland, 4101

Country

Australia

Phone

+61 402553063

Fax

harveen.k.singh1@gmail.com

Contact person for scientific queries

Name

Peter Lewindon

Address

Lady Cilento Children's Hospital, 501 Stanley St, South Brisbane, Queensland, 4101

Country

Australia

Phone

+61 7 3068 8111

Fax

p.lewindon@uq.edu.au

No information has been provided regarding IPD availability

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

No additional documents have been identified.

Trial Review

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