Desensitising Celiac Disease Patients With the Human Hookworm

NCT ID: NCT01661933

Last Updated: 2014-10-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 12 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-08-31
• Study Completion Date: 2014-03-31

Brief Summary

We have established that the hookworm Necator americanus (Na) dramatically alters the local and systemic immune landscape of the infected human host. Consistent with the principle of desensitisation, diet managed celiac disease subjects previously infected by us with Na will be invited to receive small incremental doses of gluten as pasta (3-25 mm straw of spaghetti) over 16 weeks. Each participant will then be carefully re-assessed to determine if it is appropriate to undertake a 12-week gluten challenge.

Detailed Description

Hypothesis The adaptive Th2/regulatory profile imposed by Na will promote gluten tolerance following a micro-dose desensitising programme.

Primary Aim: To determine the safety and efficacy of Na as a tolerising agent in celiac subjects

Specific Aim 1. Undertake a therapeutic pilot study comparing mucosal histopathology before and after a gluten challenge, to be preceded by a programmed desensitising micro-challenge using Na as a tolerising agent.

Specific Aim 2. Assess systemic and mucosal immune responses to gluten micro-challenge, Na infection, and gluten re-challenge throughout the pilot study, to be referenced against hookworm-naive people with treated and untreated celiac disease.

Specific Aim 3. Utilising blood and tissue from hookworm-naive celiac disease volunteers, undertake in vitro studies focusing on the effects of Na-derived excretory/secretory (ES) products on gluten-stimulated gut mucosal cell apoptosis, cytokine and gene profiles.

Conditions

Celiac Disease

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: PREVENTION
• Blinding Strategy: SINGLE

Study Groups

Necator americanus, gluten challenge

Single arm, vertical.

Group Type: EXPERIMENTAL

Necator americanus

Intervention Type: BIOLOGICAL

Previously inoculated subjects will be further inoculated as previously undertaken with 20 3rd stage infective Na larvae (10 + 10 over 4 weeks). Four weeks after the 2nd inoculation, each participant will receive a micro-dose of gluten (10 mg daily) as pasta for 8 weeks, to be followed by a low-dose of gluten (50 mg daily) for 8 weeks. After this, a detailed assessment involving upper endoscopy and duodenal biopsy will be performed before deciding on an individual case basis that it is safe for the participant to proceed to challenge. A gluten challenge of 1 G (15-20 G of pasta or a ½ slice of standard white bread) twice weekly for 12 weeks will commence.

Necator americanus

Intervention Type: BIOLOGICAL

After completion of the previously planned challenge, volunteers will be invited to extend the gluten challenge. The extension is for 4 weeks total. The gluten challenge is stepwise: gluten 10 mg daily for one week, 50 mg daily for one week and finally 3 grams daily for 2 weeks. The outcome measure is serum tissue transglutaminase to be compared before and after the intervention.

Interventions

Necator americanus

Previously inoculated subjects will be further inoculated as previously undertaken with 20 3rd stage infective Na larvae (10 + 10 over 4 weeks). Four weeks after the 2nd inoculation, each participant will receive a micro-dose of gluten (10 mg daily) as pasta for 8 weeks, to be followed by a low-dose of gluten (50 mg daily) for 8 weeks. After this, a detailed assessment involving upper endoscopy and duodenal biopsy will be performed before deciding on an individual case basis that it is safe for the participant to proceed to challenge. A gluten challenge of 1 G (15-20 G of pasta or a ½ slice of standard white bread) twice weekly for 12 weeks will commence.

Intervention Type: BIOLOGICAL

Necator americanus

After completion of the previously planned challenge, volunteers will be invited to extend the gluten challenge. The extension is for 4 weeks total. The gluten challenge is stepwise: gluten 10 mg daily for one week, 50 mg daily for one week and finally 3 grams daily for 2 weeks. The outcome measure is serum tissue transglutaminase to be compared before and after the intervention.

Intervention Type: BIOLOGICAL

Other Intervention Names

Hookworm; Hookworm

Eligibility Criteria

Inclusion Criteria

• Previously enrolled adults who received an experimental hookworm infection with diet treated celiac disease.

Exclusion Criteria

• Immune suppressive therapies

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Health and Medical Research Council, Australia

OTHER

Sponsor Role: collaborator

The Prince Charles Hospital

OTHER_GOV

Sponsor Role: lead

Responsible Party

Dr John Croese

Chief Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

John Croese, MD

Role: STUDY_DIRECTOR

The Prince Charles Hospital, Centre for Biodiscovery and Molecular Development of Therapeutics

Dianne Jones, BAppSc

Role: PRINCIPAL_INVESTIGATOR

Logan Hospital

Alexander Loukas, PhD

Role: PRINCIPAL_INVESTIGATOR

Centre for Biodiscovery and Molecular Development of Therapeutics, James Cook University

Locations

Prince Charles Hospital

Chermside, Queensland, Australia

Countries

Australia

References

Daveson AJ, Jones DM, Gaze S, McSorley H, Clouston A, Pascoe A, Cooke S, Speare R, Macdonald GA, Anderson R, McCarthy JS, Loukas A, Croese J. Effect of hookworm infection on wheat challenge in celiac disease--a randomised double-blinded placebo controlled trial. PLoS One. 2011 Mar 8;6(3):e17366. doi: 10.1371/journal.pone.0017366.

Reference Type: BACKGROUND

PMID: 21408161 (View on PubMed)

Other Identifiers

AU/3/BOBD012

Identifier Type: -

Identifier Source: org_study_id