Hookworm Therapy for Coeliac Disease

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.

Conditions

• Celiac Disease

Interventions

OTHER

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

Inadvertent gluten challenge

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

OTHER

Moderate gluten challenge

From week 36 to week 42, all participants will be on gluten 2g/day.

OTHER

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

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

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

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

Gluten free diet

From week 0 to week 12, all participants will be on a gluten free diet.

Sponsors & Collaborators

• Townsville Hospital

  collaborator OTHER_GOV

• The Prince Charles Hospital

  collaborator OTHER_GOV

• Christchurch Hospital

  collaborator OTHER

• Logan Hospital, Queensland

  collaborator OTHER_GOV

• Australian Institute of Tropical Health and Medicine

  collaborator OTHER

• QIMR Berghofer Medical Research Institute

  collaborator OTHER

• National Health and Medical Research Council, Australia

  collaborator OTHER

• James Cook University, Queensland, Australia

  lead OTHER

Principal Investigators

• John Croese, MBBS, MD · Prince Charles Hospital

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

80 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2016-09-30

Primary Completion

2019-10-31

Completion

2019-10-31

Countries

• Australia
• New Zealand

Study Locations