Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12619001092189
Ethics application status
Approved
Date submitted
12/07/2019
Date registered
8/08/2019
Date last updated
3/12/2020
Date data sharing statement initially provided
8/08/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Hookworm Therapy for young people at high risk for colorectal cancer
Scientific title
Hookworm Therapy for young people at high risk for colorectal cancer
Secondary ID [1] 298725 0
Nil known
Universal Trial Number (UTN)
U1111-1236-9296
Trial acronym
HWCRC-1
Linked study record

Health condition
Health condition(s) or problem(s) studied:
colorectal cancer 313645 0
Condition category
Condition code
Cancer 312067 312067 0 0
Bowel - Back passage (rectum) or large bowel (colon)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Open label Phase 1b proof of concept study to test for dysbiosis in small cohort of people identified as at risk for developing colorectal cancer (CRC) based on the background of conventional adenomatous polyps, and the potential of a light infection with hookworm to improve microbial richness and diversity.

All participants will receive in total 20 hookworm larvae (L3) to be applied by the study nurse as two doses of 10x L3 to the skin approximately 4 weeks apart. The L3 will be applied to a non-adherent dressing which will be placed on the forearm of the participant. The dressing will need to remain in place for the remainder of the day, and disposed of at night.

Analyses of blood and rectal mucosal immune responses, mucosal and faecal microbiomes will be undertaken pre and 12 months post hookworm infection.

The fidelity of the hookworm intervention will be monitored by participant reported incidence of a rash at the inoculation site (the first week after inoculation) and laboratory tests for the typical immune response (eosinophilia) and the presence of parasite eggs in faecal samples taken at the post-inoculation clinic visits.
Intervention code [1] 314986 0
Prevention
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 320696 0
A composite primary outcome including measurements of bacterial species richness (number of observed operational taxonomic units, OTUs) and bacterial species diversity (Shannon Index) in faecal and colon biopsy specimens, determined by shotgun metagenomic sequencing
Timepoint [1] 320696 0
Week 52 post hookworm inoculation
Secondary outcome [1] 372546 0
Number of adenomatous polyps assessed during colonoscopy at week 52 post hookworm inoculation
Timepoint [1] 372546 0
Week 52 post hookworm inoculation
Secondary outcome [2] 372547 0
General and Gastrointestinal Health Related Quality of Life Survey, designed specifically for this study
Timepoint [2] 372547 0
week 52 post hookworm inoculation
Secondary outcome [3] 372548 0
Cellular immune response in blood (complete blood count) including:
Haematocrit
Platelets
Mean Cell Volume
White cell count
Red cell count
Neutrophils
Lymphocytes
Monocytes
Eosiniphils
Basophils
Timepoint [3] 372548 0
week 52 post hookworm inoculation
Secondary outcome [4] 372549 0
An exploratory outcome analysis of the composition of the bacterial and immune profile of excised polypoid tissue, and how these may interrelate
Timepoint [4] 372549 0
week 52 post hookworm inoculation

Eligibility
Key inclusion criteria
A participant must meet the following criteria to be eligible for enrolment into the trial:
• Has provided written informed consent (PICF) and is willing to comply with all protocol scheduled visits, treatment plan, laboratory tests, and other trial procedures and in the opinion of the investigator has a good understanding of the protocol, the length of the study and the demands of the study
• Aged between 18-55 years
• Has a cumulative history of 2 or more conventional colorectal adenomata
• Has not received systemic antibiotic therapy in previous 3 months prior to baseline flexible sigmoidoscopy
• Has not received bowel preparation 3 months prior to baseline flexible sigmoidoscopy
• Is in reasonable health (ASA 1-2)
• Is not using aspirin, anti-platelet or anti-coagulant therapies
• If female, has met either of criterion “a or “b” below:
a) Is of non-childbearing potential as defined by amenorrhea for one year, or has had a hysterectomy and/or bilateral oophorectomy, or has had a tubal ligation at least 8 weeks prior to screening
b) If of childbearing potential and engaged in sexual activity with a potential for conception, must be willing to use an acceptable method of contraception
Minimum age
18 Years
Maximum age
55 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
A participant must not meet any of the following exclusion criteria.
• Has any finding at screening that in the opinion of the investigator would compromise the safety of the participant or staff or affect the ability of the participant to adhere to protocol scheduled visits, treatment plan, laboratory tests, or other trial procedures
• Has a history of current tobacco consumption or who has a history of tobacco consumption with one year prior, or a current alcohol consumption exceeding two standard drinks per day

• Has a history of intolerance, allergy or hypersensitivity to the proposed anthelmintic – mebendazole


• Has a consistent usage of anti-inflammatory drugs (including prescription and OTC medications more than twice weekly)

• Has had a diagnosis of cancer which has been in remission for less than 5 years, excluding participants with adequately treated or excised basal cell or squamous cell cancer of the skin or cervical carcinoma in situ.

• Is an employee of the sponsor or study centre or immediate family of the investigator

Study design
Purpose of the study
Prevention
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Allocation is not concealed
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
not applicable
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 1
Type of endpoint/s
Efficacy
Statistical methods / analysis
The small sample size is consistent with the huge data sets expected to be generated. There is no expectation that the study will prove definitive, but rather it is powered to provide evidence of changes to immunological and microbial platforms and trends on which to develop power calculations for future study.

For analysis of Microbiome; differences in alpha diversity will be identified using standard univariate tests and differences in beta diversity detected by the Adonis program. Differentially abundant taxa will be identified using LEfSe and ALDEx2 software, which accounts for compositional characteristics of sequence data. Longitudinal data will be analysed using linear mixed-effects regression. Longitudinal comparisons will study changes in diversity and community composition and microbial functions and pathways will be analysed in a similar approach.

For analysis of host gene expression: Sequence data derived from paired-end Illumina sequencing (HiSeq) will be mapped to the currently available entire human genome sequence and annotated. Corresponding proteins will be mapped to conserved biological pathways and molecules putatively involved in immune functions will be identified. Levels of transcription of genes encoding molecules involved in immunological mechanisms will be assessed by normalizing the numbers of raw reads mapping to individual assembled transcripts for sequence length (i.e. reads per kb per million reads, RPKM). Differentially expressed genes between each genotype and time point will be categorized according to Gene Ontology terms and the enrichment of each term will be calculated using the modified Fisher Extract Test implemented in FatiGO. The Ingenuity Pathway Analysis software will be used to identify network interactions between DEGs and other molecules in the IPA knowledge base, as well as to determine the top biological functions associated with these networks.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
4/01/2021
Actual
Date of last participant enrolment
Anticipated
4/10/2021
Actual
Date of last data collection
Anticipated
4/07/2022
Actual
Sample size
Target
20
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 14220 0
The Prince Charles Hospital - Chermside
Recruitment postcode(s) [1] 27208 0
4032 - Chermside

Funding & Sponsors
Funding source category [1] 303279 0
University
Name [1] 303279 0
James Cook University
Country [1] 303279 0
Australia
Primary sponsor type
University
Name
James Cook University
Address
16-88 McGregor Rd
Smithfield QLD Australia 4878
Country
Australia
Secondary sponsor category [1] 303297 0
Hospital
Name [1] 303297 0
The Prince Charles Hospital
Address [1] 303297 0
Rode Rd
Chermside QLD 4032 Australia
Country [1] 303297 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 303816 0
The Prince Charles Hospital Human Research Ethics Committee
Ethics committee address [1] 303816 0
Ethics committee country [1] 303816 0
Australia
Date submitted for ethics approval [1] 303816 0
10/01/2019
Approval date [1] 303816 0
03/06/2019
Ethics approval number [1] 303816 0
50127

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 94910 0
Dr Tony Rahman
Address 94910 0
Director Gastroenterology, The Prince Charles Hospital
Rode Road, Chermside, 4034, QLD, Australia
Country 94910 0
Australia
Phone 94910 0
+61 7 22114527
Fax 94910 0
Email 94910 0
[email protected]
Contact person for public queries
Name 94911 0
Paul Giacomin
Address 94911 0
AITHM Building E5, James Cook University Cairns Campus
McGregor Rd Smithfield, QLD 4878 Australia
Country 94911 0
Australia
Phone 94911 0
+61 7 42321868
Fax 94911 0
Email 94911 0
[email protected]
Contact person for scientific queries
Name 94912 0
Paul Giacomin
Address 94912 0
AITHM Building E5, James Cook University Cairns Campus
McGregor Rd Smithfield, QLD 4878 Australia
Country 94912 0
Australia
Phone 94912 0
+61 7 42321868
Fax 94912 0
Email 94912 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Individual data will be held in a secure database. Published data will be accessible but not accessible as individual data.


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.