Clinical trial NCT01661933: Desensitising Celiac Disease Patients With the Human Hookworm
Official title: Combining Necator Americanus With Trace Gluten to Restore Tolerance in Coeliac Disease: a Pilot Clinical and a Detailed in Vitro Immunological Study.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Celiac Disease
Keywords: celiac disease
hookworm
probiotic
Lead sponsor: The Prince Charles Hospital
Sponsor class: OTHER_GOV
Collaborators: name: National Health and Medical Research Council, Australia
First posted: 2012-08-10
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

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.

Eligibility criteria: Inclusion Criteria:

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

Exclusion Criteria:

* Immune suppressive therapies

Primary outcomes:
measure: Duodenal Villus Height:Crypt Depth
timeFrame: Week -24 to -36
Secondary outcomes:
measure: Intraepithelial Lymphocyte Count
timeFrame: Week-24 and -36
measure: Number of Participants With 2 Points Increase in Marsh Score Post GC-1g
timeFrame: Longitudinal change between week-24 and week-36
measure: Serum Anti-tissue Transglutaminase Antibodies Measured as International Units/mL (IU/mL)
timeFrame: Anti-tTG IU/mL levels pre-trial, mid-trial and after 3 gram/day gluten challenge
Other outcomes:
Locations:
city: Chermside
country: Australia
facility: Prince Charles Hospital
state: Queensland
Study officials:
affiliation: The Prince Charles Hospital, Centre for Biodiscovery and Molecular Development of Therapeutics
name: John Croese, MD
role: STUDY_DIRECTOR
affiliation: Logan Hospital
name: Dianne Jones, BAppSc
role: PRINCIPAL_INVESTIGATOR
affiliation: Centre for Biodiscovery and Molecular Development of Therapeutics, James Cook University
name: Alexander Loukas, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.