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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] 292501 0
Nil known
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Ulcerative Colitis 304134 0
Primary Sclerosing Cholangitis 304135 0
Condition category
Condition code
Oral and Gastrointestinal 303470 303470 0 0
Inflammatory bowel disease
Oral and Gastrointestinal 303594 303594 0 0
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] 298685 0
Not applicable
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 302839 0
At inital enrollment and 3 months later we will systematically assess; mucosal healing, which will be assessed by colon biopsy sample analysis.
Timepoint [1] 302839 0
3 months
Secondary outcome [1] 337209 0
Identify the changes in mucosal cytokine T regulatory profile which will be assessed from mucosal samples.
Timepoint [1] 337209 0
3 months
Secondary outcome [2] 337470 0
Faecal microbiome by performing stool sample analysis
Timepoint [2] 337470 0
5 years
Secondary outcome [3] 337540 0
Mucosal microbiome by performing mucosal tissue analysis
Timepoint [3] 337540 0
5 years
Secondary outcome [4] 337565 0
Assessment of clinical response to treatment with faecal calprotectin (stool sample) and C reactive protein (blood sample)
Timepoint [4] 337565 0
5 years
Secondary outcome [5] 337567 0
Response of PSC to treatment by reviewing imaging such as MRCP (Magnetic resonance cholangiopancreatography)
Timepoint [5] 337567 0
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?
No
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] 297072 0
Self funded/Unfunded
Name [1] 297072 0
Nil funding
Country [1] 297072 0
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] 296076 0
None
Name [1] 296076 0
Nil
Address [1] 296076 0
Nil
Country [1] 296076 0

Ethics approval
Ethics application status
Not yet submitted
Ethics committee name [1] 298251 0
Children's Health Queensland Ethics Committee
Ethics committee address [1] 298251 0
Lady Cilento Children's Hospital, 501 Stanley St, South Brisbane, Queensland, 4101
Ethics committee country [1] 298251 0
Australia
Date submitted for ethics approval [1] 298251 0
31/08/2017
Approval date [1] 298251 0
Ethics approval number [1] 298251 0

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 71502 0
A/Prof Peter Lewindon
Address 71502 0
Lady Cilento Children's Hospital, 501 Stanley St, South Brisbane, Queensland, 4101
Country 71502 0
Australia
Phone 71502 0
+61 7 3068 8111
Fax 71502 0
Email 71502 0
[email protected]
Contact person for public queries
Name 71503 0
Harveen Singh
Address 71503 0
Lady Cilento Children's Hospital, 501 Stanley St, South Brisbane, Queensland, 4101
Country 71503 0
Australia
Phone 71503 0
+61 402553063
Fax 71503 0
Email 71503 0
[email protected]
Contact person for scientific queries
Name 71504 0
Peter Lewindon
Address 71504 0
Lady Cilento Children's Hospital, 501 Stanley St, South Brisbane, Queensland, 4101
Country 71504 0
Australia
Phone 71504 0
+61 7 3068 8111
Fax 71504 0
Email 71504 0
[email protected]

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

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