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Trial registered on ANZCTR


Registration number
ACTRN12620000956909
Ethics application status
Approved
Date submitted
3/08/2020
Date registered
25/09/2020
Date last updated
25/09/2020
Date data sharing statement initially provided
25/09/2020
Type of registration
Retrospectively registered

Titles & IDs
Public title
Hookworm therapy for maintenance in ulcerative colitis:
Scientific title
Hookworm therapy for maintenance in ulcerative colitis: A placebo-controlled pilot study investigating the feasibility and efficacy of hookworm inoculation in patients with ulcerative colitis currently in remission
Secondary ID [1] 301703 0
None
Universal Trial Number (UTN)
U1111-1250-6894
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Ulcerative Colitis 318157 0
Condition category
Condition code
Oral and Gastrointestinal 316177 316177 0 0
Inflammatory bowel disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
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.
Intervention code [1] 318219 0
Treatment: Other
Comparator / control treatment
Capsaicin cream 0.075%: A total of 10 participants at week 0 will have Capsaicin cream 0.075% applied to their skin on their forearm using a white dressing. The dressing will stay in place for the remainder of the day. Capsaicin cream is an ideal placebo as the sensation to the skin is similar to a hookworm. 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.
Control group
Placebo

Outcomes
Primary outcome [1] 324615 0
Maintenance of clinical remission at week 52 defined as faecal calprotectin (FC) <200, a commonly used biological marker of gut inflammation measured from a stool sample, and Simple Clinical Colitis Activity Index (SCCAI) <5, a commonly used clinical measure of disease activity
Timepoint [1] 324615 0
52 weeks post administering hookworm/placebo
Primary outcome [2] 324937 0
To asses feasibility of recruiting, screening and randomising participants
The following will be collected to answer this outcome:
1) Recruitment/uptake rate
2) Drop-out rates over the course of the study and reasons behind drop-out
3) Participant burden regarding scheduling/density of study visits and measures taken.
4) Whether participants can be blinded as to their study arm (intervention or control)
a. Self-report of suspected group allocation (at time of application, 4w, 12w & end of follow-up)
5) Specific to the intervention group- Rate of successful infection at 12 weeks
Timepoint [2] 324937 0
These elements will be assessed through general study management processes (1, 2 and 5) and using exit interviews/surveys on participation experience at the end of study visit (3 and 4).
Secondary outcome [1] 385220 0
Time in clinical remission from administration of hookworm/placebo defined as faecal calprotectin (FC) <200, a commonly used biological marker of gut inflammation measured from a stool sample, and Simple Clinical Colitis Activity Index (SCCAI)<5, a commonly used clinical measure of disease activity
Timepoint [1] 385220 0
Assessed every 2 weeks for first 2 months, then monthly for 2 months, then 3 monthly until week 52 post intervention, with additional unscheduled assessments as required.
Secondary outcome [2] 385221 0
Adverse events experienced. Examples of possible adverse reactions include abdominal discomfort, rash at site of hookworm administration and iron deficiency anaemia. Assessments of adverse events include interviews, questionnaires, physical examination, and blood tests
Timepoint [2] 385221 0
Assessed every 2 weeks for first 2 months, then monthly for 2 months, then 3 monthly, with additional unscheduled assessments as required.

Eligibility
Key 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
Minimum age
18 Years
Maximum age
70 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment outside Australia
Country [1] 22805 0
New Zealand
State/province [1] 22805 0
Hutt Valley/Wellington

Funding & Sponsors
Funding source category [1] 306140 0
Other
Name [1] 306140 0
Malaghan Institute of Medical Research
Address [1] 306140 0
Victoria University
Kelburn
Wellington 6012
Country [1] 306140 0
New Zealand
Primary sponsor type
Other
Name
Malaghan Institute of Medical Research
Address
Victoria University
Kelburn
Wellington 6012
Country
New Zealand
Secondary sponsor category [1] 306852 0
None
Name [1] 306852 0
Nil
Address [1] 306852 0
Nil
Country [1] 306852 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 306357 0
Health and Disability Ethics Committee
Ethics committee address [1] 306357 0
Ministry of Health
Health and Disability Ethics Committees
PO Box 5013
Wellington 6140
Ethics committee country [1] 306357 0
New Zealand
Date submitted for ethics approval [1] 306357 0
Approval date [1] 306357 0
06/07/2020
Ethics approval number [1] 306357 0

Summary
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.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 103602 0
Dr Stephen Inns
Address 103602 0
Gastroenterology Department
Hutt Hospital
638 High St
Boulcott
Lower Hutt 5010
Country 103602 0
New Zealand
Phone 103602 0
+64274446732
Fax 103602 0
Email 103602 0
Stephen.inns@otago.ac.nz
Contact person for public queries
Name 103603 0
Dr Thomas Mules
Address 103603 0
Gastroenterology Department
Hutt Hospital
638 High St
Boulcott
Lower Hutt 5010
Country 103603 0
New Zealand
Phone 103603 0
+6445666999
Fax 103603 0
Email 103603 0
worms4colitis@malaghan.org.nz
Contact person for scientific queries
Name 103604 0
Dr Thomas Mules
Address 103604 0
Gastroenterology Department
Hutt Hospital
638 High St
Boulcott
Lower Hutt 5010
Country 103604 0
New Zealand
Phone 103604 0
+6445666999
Fax 103604 0
Email 103604 0
worms4colitis@malaghan.org.nz

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
What supporting documents are/will be available?
No other documents available
Summary results
No Results