ANZCTR - Registration

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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

7/09/2023

Date data sharing statement initially provided

25/09/2020

Date results provided

7/09/2023

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]

None

Universal Trial Number (UTN)

U1111-1250-6894

Trial acronym

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Ulcerative Colitis

Condition category

Condition code

Oral and Gastrointestinal

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]

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]

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]

52 weeks post administering hookworm/placebo

Primary outcome [2]

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]

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]

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]

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]

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]

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

Sex

Both males and females

Can healthy volunteers participate?

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

Completed

Date of first participant enrolment

Anticipated

Actual

3/08/2020

Date of last participant enrolment

Anticipated

Actual

1/07/2021

Date of last data collection

Anticipated

Actual

1/07/2022

Sample size

Target

Accrual to date

Final

Recruitment outside Australia

Country [1]

New Zealand

State/province [1]

Hutt Valley/Wellington

Funding & Sponsors

Funding source category [1]

Other

Name [1]

Malaghan Institute of Medical Research

Address [1]

Victoria University
Kelburn
Wellington 6012

Country [1]

New Zealand

Funding source category [2]

Government body

Name [2]

Health Research Council of NZ

Address [2]

Health Research Council of New Zealand
South Tower Level 1/110 Symonds Street, Grafton, Auckland 1010

Country [2]

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]

None

Name [1]

Nil

Address [1]

Nil

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Health and Disability Ethics Committee

Ethics committee address [1]

Ministry of Health
Health and Disability Ethics Committees
PO Box 5013
Wellington 6140

Ethics committee country [1]

New Zealand

Date submitted for ethics approval [1]

Approval date [1]

06/07/2020

Ethics approval number [1]

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

Dr Stephen Inns

Address

Gastroenterology Department
Hutt Hospital
638 High St
Boulcott
Lower Hutt 5010

Country

New Zealand

Phone

+64274446732

Fax

Stephen.inns@otago.ac.nz

Contact person for public queries

Name

Thomas Mules

Address

Gastroenterology Department
Hutt Hospital
638 High St
Boulcott
Lower Hutt 5010

Country

New Zealand

Phone

+6445666999

Fax

worms4colitis@malaghan.org.nz

Contact person for scientific queries

Name

Thomas Mules

Address

Gastroenterology Department
Hutt Hospital
638 High St
Boulcott
Lower Hutt 5010

Country

New Zealand

Phone

+6445666999

Fax

worms4colitis@malaghan.org.nz

Data sharing statement

Will individual participant data (IPD) for this trial be available (including data dictionaries)?

No/undecided IPD sharing reason/comment

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

Source	Title	Year of Publication	DOI
Embase	The yin and yang of human soil-transmitted helminth infections.	2021	https://dx.doi.org/10.1016/j.ijpara.2021.11.001

N.B. These documents automatically identified may not have been verified by the study sponsor.

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Documents added manually

Documents added automatically