NCT01661933

Desensitising Celiac Disease Patients With the Human Hookworm

Combining Necator Americanus With Trace Gluten to Restore Tolerance in Coeliac Disease: a Pilot Clinical and a Detailed in Vitro Immunological Study.

• Status: Completed
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 12 (actual)
• Sponsor: The Prince Charles Hospital · Other Government
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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

Interventions

Type	Name	Description
BIOLOGICAL	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.
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.

Timeline

• Start date: 2012-08-01
• Primary completion: 2014-03-01
• Completion: 2014-03-01
• First posted: 2012-08-10
• Last updated: 2014-10-20
• Results posted: 2014-10-13

Locations

1 site across 1 country: Australia