None listed
Conditions
Brief summary
This study aims to evaluate low-dose hookworm therapy in adults who are at a high risk of developing colorectal cancer (CRC). The study will assess how useful the hookworms are in improving the richness and diversity of bacterial species within the gut, which may be a preventive measure against the development of CRC. Who is it for? You may be eligible to join this study if you are aged 18- 55 and have a cumulative history of 2 or more conventional colorectal polyps. Study details All participants will have 10 hookworms applied to their skin and then again 4 weeks later, this will provide a mild infection to the gut. The study will involve taking a variety of biological samples before the infection (including, blood, stool and rectal tissue specimens) and again after approximately 6 and 12 months. These specimens will be subjected to laboratory analysis to determine if the hookworm infection changed the types of bacteria within the gut and how this relates to gut inflammation. If any pre-cancerous tissue is identified during the surveillance period, it will be removed and similarly inspected for bacteria and inflammation. All participants will be required to undertake quality of life questionnaires and blood samples will be carefully analysed by commercial pathology providers to monitor safety of the hookworm infections.
Interventions
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
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.
Sponsors
James Cook University
Study design
Allocation
Non-randomised trial
Intervention model
Single group
Primary purpose
Prevention
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to 55 Years
Healthy volunteers
No
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
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
Outcome results
None listed