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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT02754609




Registration number
NCT02754609
Ethics application status
Date submitted
26/04/2016
Date registered
28/04/2016
Date last updated
13/02/2020

Titles & IDs
Public title
Hookworm Therapy for Coeliac Disease
Scientific title
Hookworm Therapy for Coeliac Disease: A Phase 1B Safety and Dose-ranging Clinical Trial Examining Sustained Gluten Consumption in Hookworm-naive and Hookworm-infection People With Coeliac Disease
Secondary ID [1] 0 0
CT-2016-CTN-01363-1
Universal Trial Number (UTN)
Trial acronym
NainCeD-3
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Celiac Disease 0 0
Condition category
Condition code
Infection 0 0 0 0
Other infectious diseases
Inflammatory and Immune System 0 0 0 0
Autoimmune diseases
Oral and Gastrointestinal 0 0 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - Gluten micro-challenge
Other interventions - Inadvertent gluten challenge
Other interventions - Moderate gluten challenge
Other interventions - Liberal diet
Other interventions - Necator americanus-hookworm larvae L3-10
Other interventions - Tabasco® Sauce
Other interventions - Necator americanus-hookworm larvae L3-20
Other interventions - Gluten free diet

Experimental: Necator americanus-hookworm larvae L3-10 - A total of 40 participants week 0 and week 8 will have low dose hookworms present in 2-3 drops of water applied to their skin and then covered in a light dressing. The hookworms are Necator americanus-hookworm larvae L3; 10 L3 in 200 microliter (uL) of deionized water presented in an Eppendorf tube. All participants will undergo interventions of Gluten free diet, Gluten micro-challenge, Inadvertent gluten challenge and Moderate gluten challenge. At week 42, participants will have the option of going on the liberal diet.

Placebo Comparator: Tabasco® Sauce - A total of 10 participants at week 0 and week 8 will have Tabasco® Sauce present in 2-3 drops of water applied to their skin and covered in a light dressing. Tabasco® Sauce is an ideal placebo as the sensation to the skin is similar to a hookworm. All participants will undergo interventions of Gluten free diet, Gluten micro-challenge, Inadvertent gluten challenge and Moderate gluten challenge.

Experimental: Necator americanus-hookworm larvae L3-20 - A total of 10 participants at week 0 and week 8 will have medium dose hookworms present in 2-3 drops of water applied to their skin and then covered in a light dressing. The hookworms are Necator americanus-hookworm larvae L3; 20 L3 in 200 uL of deionized water presented in an Eppendorf tube. All participants will undergo interventions of Gluten free diet, Gluten micro-challenge, Inadvertent gluten challenge and Moderate gluten challenge. At week 42, participants will have the option of going on the liberal diet.


Other interventions: Gluten micro-challenge
From week 12 to week 24, all participants will start a gluten micro-challenge from 10mg/day for the first 2 weeks escalating over the this period to 50mg/day at the end of week 24.

Other interventions: Inadvertent gluten challenge
From week 24 to week 36, all participants will be on gluten 50mg/day and 1g twice weekly.

Other interventions: Moderate gluten challenge
From week 36 to week 42, all participants will be on gluten 2g/day.

Other interventions: Liberal diet
From week 42, all participants will be unblinded and those who have received hookworm therapy have the option to go on a liberal diet of more than 10g of gluten/day from week 42 to week 94.

Other interventions: Necator americanus-hookworm larvae L3-10
A total of 40 participants at week 0 and week 8 will have hookworms L3-10 present in 2-3 drops of water applied to their skin and then covered in a light dressing.

Other interventions: Tabasco® Sauce
Arm: Placebo Comparator: Tabasco® Sauce A total of 10 participants at week 0 and week 8 will have Tabasco® Sauce present in 2-3 drops of water applied to their skin and covered in a light dressing

Other interventions: Necator americanus-hookworm larvae L3-20
A total of 40 participants at week 0 and week 8 will have hookworms L3-20 present in 2-3 drops of water applied to their skin and then covered in a light dressing.

Other interventions: Gluten free diet
From week 0 to week 12, all participants will be on a gluten free diet.
Intervention code [1] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Safety of 30-week gluten challenge
Timepoint [1] 0 0
44 weeks
Secondary outcome [1] 0 0
Difference in mucosal intraepithelial lymphocyte count between baseline (week -2) and week 42
Timepoint [1] 0 0
14 weeks
Secondary outcome [2] 0 0
Difference in V:C ratio between baseline (week -2) and week 42
Timepoint [2] 0 0
14 weeks
Secondary outcome [3] 0 0
Difference in mucosal intraepithelial lymphocyte count between baseline (week -2) and week 42
Timepoint [3] 0 0
38 weeks
Secondary outcome [4] 0 0
Difference in mucosal intraepithelial lymphocyte count between baseline (week -2) and week 36
Timepoint [4] 0 0
44 weeks
Secondary outcome [5] 0 0
Difference in mucosal intraepithelial lymphocyte count between baseline (week -2) and week 94
Timepoint [5] 0 0
96 weeks
Secondary outcome [6] 0 0
Difference in Celiac Symptom Index (CSI Questionnaire) between baseline (week 0) and week 36
Timepoint [6] 0 0
36 weeks
Secondary outcome [7] 0 0
Difference in Celiac Symptom Index (CSI Questionnaire) between baseline (week 0) and week 42
Timepoint [7] 0 0
42 weeks
Secondary outcome [8] 0 0
Difference in Celiac Symptom Index (CSI Questionnaire) between baseline (week 0) and week 94
Timepoint [8] 0 0
94 weeks
Secondary outcome [9] 0 0
Difference in Celiac-Quality of Life Score (QOL questionnaire) between baseline (week 0) and week 36
Timepoint [9] 0 0
36 weeks
Secondary outcome [10] 0 0
Difference in Celiac-Quality of Life Score (QOL questionnaire) between baseline (week 0) and week 42
Timepoint [10] 0 0
42 weeks
Secondary outcome [11] 0 0
Difference in Celiac-Quality of Life Score (QOL questionnaire) between baseline (week 0) and week 94
Timepoint [11] 0 0
94 weeks
Secondary outcome [12] 0 0
Difference in Immunoglobulin A tissue transaminase (tTG) between baseline (week -4) and week 36
Timepoint [12] 0 0
40 weeks
Secondary outcome [13] 0 0
Difference in Immunoglobulin A tissue transaminase (tTG) between baseline (week -4) and week 42
Timepoint [13] 0 0
46 weeks
Secondary outcome [14] 0 0
Difference in Immunoglobulin A tissue transaminase (tTG) between baseline (week -4) and week 94
Timepoint [14] 0 0
98 weeks
Secondary outcome [15] 0 0
Difference in V:C ratio between baseline (week -2) and week 24
Timepoint [15] 0 0
38 weeks
Secondary outcome [16] 0 0
Difference in V:C ratio between baseline (week -2) and week 94
Timepoint [16] 0 0
96 weeks
Secondary outcome [17] 0 0
Difference in V:C ratio between baseline (week -2) and week 12
Timepoint [17] 0 0
14 weeks

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 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.

2. Aged between 18-80 (at time of consent);

3. Have a pre-treatment histological diagnosis of Marsh grade 3 CeD;

4. Have a pre-trial V:C >2.0;

5. Have elevated tTG or endomysial Ab +ve pre-trial;

6. Have been adherent to a gluten-free diet for >6 months pre-enrolment;

7. Have a tTG <20 IU/mL (normal <15) at screening;

8. Have a CSI <35 at screening;

9. If female, has met either of criterion "a or b" below:

1. If of non-childbearing potential, has met 1 of the following - Amenorrheic for at
least 2 years, or has had a hysterectomy and/or bilateral oophorectomy at least 8
weeks prior to screening, or has had a tubal ligation at least 8 weeks prior to
screening.

2. If of childbearing potential, must be willing to use the acceptable methods of
contraception and abide by the timelines as indicated

10. In the opinion of the Investigator is in good general health
Minimum age
18 Years
Maximum age
80 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1. Have any finding at screening that in the opinion of the Investigator or medical
monitor would compromise the safety of the Participant or affect their ability to
adhere to protocol scheduled visits, treatment plan, laboratory tests, and other trial
procedures.

2. Have participated in any other clinical trial and/or have received an investigational
drug or device within 30 days of screening.

3. Have history or current evidence of any of the following: compromised respiratory
function (chronic obstructive pulmonary disease, respiratory depression, signs or
symptoms of hypoxia at screening); thyroid pathology (unless stabilized and euthyroid
for >3 months at the time of screening); hepatitis B, hepatitis C, or human
immunodeficiency virus (HIV) infection; evidence of clinically significant chronic
cardiac, hepatic or renal disease; psychiatric illness (poorly controlled); seizure
disorder or any other chronic health issues that in the opinion of the Investigator
would exclude the Participant from the trial.

4. History of substance abuse or current substance abuse that in the opinion of the
Investigator would exclude the Participant from the trial.

5. Have a history of intolerance, allergy or hypersensitivity to the proposed placebo -
Tabasco® Sauce or any of its known ingredients.

6. Have a history of intolerance, allergy or hypersensitivity to the proposed
anthelmintic - mebendazole.

7. Have a history of intolerance, allergy or hypersensitivity to the proposed chemicals
used in preparation of N.americanus - amphotericin B and Betadine that in the opinion
of the Investigator would exclude the Participant from the trial.

8. Current requirement for consistent use of anti-inflammatory drugs (includes
prescription and over the counter medication >2 doses per week, that in the opinion of
the Investigator would significantly alter the Participant's immunity), aspirin
exceeding 125 mg/day or the use of immunotherapeutics;

9. Diagnosis of cancer which has been in remission for < 5 years, excluding Participants
with adequately treated or excised non-metastatic basal cell or squamous cell cancer
of the skin or cervical carcinoma in situ.

10. Poor venous access making the Participant unable to comply with the safety laboratory
testing and/or endoscopy sedation requirements.

11. Are an employee of the Sponsor, Investigator or study centre or immediate family of
such employees or the Investigator.

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
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/09/2016
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/10/2019
Sample size
Target
Accrual to date
Final
54
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 0 0
Prince Charles Hospital - Brisbane
Recruitment hospital [2] 0 0
Logan Hospital - Logan
Recruitment hospital [3] 0 0
Townsville Hospital - Townsville
Recruitment postcode(s) [1] 0 0
4032 - Brisbane
Recruitment postcode(s) [2] 0 0
4131 - Logan
Recruitment postcode(s) [3] 0 0
4812 - Townsville
Recruitment outside Australia
Country [1] 0 0
New Zealand
State/province [1] 0 0
Christchurch

Funding & Sponsors
Primary sponsor type
Other
Name
James Cook University, Queensland, Australia
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
Townsville Hospital
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Other
Name [2] 0 0
The Prince Charles Hospital
Address [2] 0 0
Country [2] 0 0
Other collaborator category [3] 0 0
Other
Name [3] 0 0
Christchurch Hospital
Address [3] 0 0
Country [3] 0 0
Other collaborator category [4] 0 0
Other
Name [4] 0 0
Logan Hospital, Queensland
Address [4] 0 0
Country [4] 0 0
Other collaborator category [5] 0 0
Other
Name [5] 0 0
Australian Institute of Tropical Health and Medicine
Address [5] 0 0
Country [5] 0 0
Other collaborator category [6] 0 0
Other
Name [6] 0 0
QIMR Berghofer Medical Research Institute
Address [6] 0 0
Country [6] 0 0
Other collaborator category [7] 0 0
Other
Name [7] 0 0
National Health and Medical Research Council, Australia
Address [7] 0 0
Country [7] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
This trial is a Phase 1b multicentre, multinational, randomized, double-blind with
single-blind arm and open label extension phase, placebo controlled, clinical trial
evaluating the safety and predictability of an escalating gluten consumption to activate
Coeliac Disease (CeD) in (a) a small cohort of people with diet-managed CeD treated with a
placebo (n=10), and in (b) cohorts following low (L3-10; n=40) and medium (L3-20; n=10) dose
hookworm inocula.

The investigators 4 aims for the study are:

Aim 1: Undertake a multiple-phase and escalating gluten challenge assessing safety to gluten
exposure in hookworm-naïve and hookworm-infected people with CeD.

Aim 2: This phase Ib study recognizes that the evidence supporting this novel intervention is
rudimentary and addresses amongst others the following questions: (a) The importance of L3
dose on Participant health, and (b) the importance of L3 dose on the safety of escalating
gluten challenge and (c) the need for a comparator group should a phase II trial be
warranted.

Aim 3: Examine the changes in intestinal T cell responses induced by hookworm infection and
gluten exposure.

Aim 4: Assess the impact of hookworm infection and purified hookworm-derived proteins on
gluten peptide-specific immune responses ex vivo.
Trial website
https://clinicaltrials.gov/ct2/show/NCT02754609
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
John Croese, MBBS, MD
Address 0 0
Prince Charles Hospital
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries