None listed
Conditions
Brief summary
The study population will include 20 eligible patients with ulcerative colitis who currently have well controlled disease on 5-aminosalicylic acid (5-ASA) alone, as determined by the Simple Clinical Colitis Activity Index (SCCAI), a commonly used clinical measure of disease activity; and the faecal calprotectin (FC), a commonly used biological marker of gut inflammation measured from a stool sample. The study’s primary outcome is maintenance of clinical remission (FC <200 and SCCAI<5) at week 52. Secondary outcomes are time in remission (FC<200 and SCCAI<5) from start of treatment, and the difference in adverse events between hookworm exposed and placebo exposed patients at week 52. This study will also assess the feasibility of recruiting, screening and randomising participants for such a study, and the immunological effects of controlled hookworm infection. After informed consent Participants will be screened for eligibility. Eligible Participants will be randomised in a double-blind fashion to receive either 30 hookworm larvae in the infective L3 lifecycle phase (L3) or a placebo consisting of Capascian cream, applied directly to the skin of the forearm. All patients will cease 5-ASA therapy at week 12. During the study Participants have scheduled study visits every 2 to 12 weeks, with unscheduled visits performed as needed. Participants will discontinue with study if they develop; a flare of ulcerative colitis (as defined by SCCAI<5 and FC>200), recurrent mild AE or a SAE that in the Investigators opinion would impact on the Participants ability to continue the study, pregnancy or request of the Participant to withdraw. They will complete a termination visit, become un-blinded, treated with deworming therapy (mebendazole 100mg BD for 3 days) if in the interventional arm and their IBD managed as per standard care. Participants remaining in the study at 52 weeks after randomisation will be un-blinded. Participants in the interventional arm will be given the opportunity of undertake a continuation phase where they are monitored every 4 to 12 weeks. Participants in the interventional arm not undertaking the continuation phase will be treated with mebendazole and have their IBD managed as per standard care. Participants in the placebo arm will have their IBD managed as per standard care.
Interventions
30 Necator americanus-hookworm larvae in L3 phase: At week 0 a total of 10 participants will have low dose hookworms present in 2-3 drops of water applied to their skin on their forearm using a white dressing. No special preparation of the forearm skin is required. The hookworms are 30 Necator americanus-hookworm larvae in the infective L3 lifecycle phase in 200 microliter (uL) of deionized water presented in a small plastic microtube. They will be delivered by a trained researcher at the resear
30 Necator americanus-hookworm larvae in L3 phase: At week 0 a total of 10 participants will have low dose hookworms present in 2-3 drops of water applied to their skin on their forearm using a white dressing. No special preparation of the forearm skin is required. The hookworms are 30 Necator americanus-hookworm larvae in the infective L3 lifecycle phase in 200 microliter (uL) of deionized water presented in a small plastic microtube. They will be delivered by a trained researcher at the research centre. The dressing will stay in place for the remainder of the day. Hookworm is delivered only once during the study. All participants cease their 5-aminosalicylic acid (5-ASA) at week 12. Participants will be monitored with regular clinic visits (every 2 weeks for first 2 months, then monthly for 2 months, then 3 monthly, with unscheduled visits as required) until an ulcerative colitis flare occurs, or week 52.
Sponsors
Malaghan Institute of Medical Research
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
All
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
1) Has provided written informed consent and is willing to comply with all protocol scheduled visits, treatment plan, laboratory tests, and other trial procedures. 2) Aged 18-70 3) Have an endoscopic and histological diagnosis of ulcerative colitis for > 3 months 4) Ulcerative colitis is in remission (On stable dose of maintenance therapy for previous 3 months, and screening SCCAI<5 and faecal calprotectin<100) 5) Current ulcerative colitis maintenance medication is 5-aminosalicylic acid (5-ASA) (oral or rectal preparation) only
Exclusion criteria
1) Anticipated to require endoscopic, radiological or surgical intervention during the study 2) Women who are pregnant, breast feeding, or planning on becoming pregnant during the study. All woman must have a negative pregnancy test prior to randomisation. 3) Woman of childbearing age not using adequate contraception (abstinence, oral contraceptive, intrauterine device, barrier method, surgical sterilisation, Depo-Provera, hormonal implant) 4) Asthma or asthma symptoms requiring any treatment within 5 years of screening visit 5) Eosinophilic lung disease or other active respiratory disorder 6) Current or recent serious systemic disorder including clinically significant impairment in cardiac, pulmonary, renal, endocrine, haematological, or neurologic function, based on investigator discretion 7) Currently receiving the following medication: - Immunosuppressant medication (other than 5ASA) within 3 months from day 0 (including but not limited to prednisone, budesonide, thiopurines, methotrexate, biologics) - NSAIDs within 2 weeks from day 0 - Treatment with anti-parasitic or antibiotics medication within 2 weeks prior to day 0 8) Presence of any of the following laboratory parameters at screening - Hb <100 - WCC <4 or >20 9) Known immunodeficiency disease including HIV, HBV, HCV 10) Evidence of infective colitis including C.diff, bacterial enteric pathogens or pathogenic ova/parasites 11) History of malignancy within the past 5 years, excluding BCC or SCC of the skin or cervical carcinoma in situ 12) History of colonic dysplasia 13) Other clinically significant disease that could interfere with protocol compliance or interpretation of results 14) Intolerance, allergy or hypersensitivity to capsaicin or ingredients 15) Intolerance to mebendazole 16) Intolerance to the chemicals used to prepare N.americanus
Outcome results
None listed