Desensitising Celiac Disease Patients With the Human Hookworm

NCT01661933 | Completed Phase 1 Results DMC

• 1 other identifier: AU/3/BOBD012
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

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.

Conditions

Celiac Disease

Keywords

celiac disease; hookworm; probiotic

Outcome Measures

Primary Outcomes (1)

• Duodenal Villus Height:Crypt Depth

  Biopsies were fixed in neutral buffered formalin, processed and carefully orientated and embedded in paraffin wax. Sections (3 µm) were stained with H\&E. Slides from both time-points were de-identified, shuffled and graded by Dr John Croese after which results from poorly orientated slides were verified by Dr Andrew Clouston. The Vh:Cd ratios were measured on 5 randomly selected well-orientated sites. The null hypothesis is that hookworm infection will not protect against mucosal damage following 12-week exposure to gluten in celiac disease.

  Week -24 to -36

Secondary Outcomes (3)

• Intraepithelial Lymphocyte Count

  Week-24 and -36

• Number of Participants With 2 Points Increase in Marsh Score Post GC-1g

  Longitudinal change between week-24 and week-36

• Serum Anti-tissue Transglutaminase Antibodies Measured as International Units/mL (IU/mL)

  Anti-tTG IU/mL levels pre-trial, mid-trial and after 3 gram/day gluten challenge

Study Arms (1)

Necator americanus, gluten challenge

EXPERIMENTAL

Single arm, vertical.

Biological: Necator americanus

Interventions

Necator americanus 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.

Also known as: Hookworm

Necator americanus, gluten challenge

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• Immune suppressive therapies

Sponsors & Collaborators

• The Prince Charles Hospital: lead
• National Health and Medical Research Council, Australia: collaborator

Study Sites (1)

Prince Charles Hospital

Chermside, Queensland, 4032, Australia

Location

Related Publications (1)

• 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.

  PMID: 21408161 BACKGROUND

MeSH Terms

Conditions

Celiac Disease; Ancylostomiasis

Interventions

ASP-1 protein, Necator americanus

Condition Hierarchy (Ancestors)

Malabsorption Syndromes; Intestinal Diseases; Gastrointestinal Diseases; Digestive System Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases; Hookworm Infections; Strongylida Infections; Secernentea Infections; Nematode Infections; Helminthiasis; Parasitic Diseases; Infections

Limitations and Caveats

Open study. Small number. Historical controls.

Results Point of Contact

• Title: Dr John Croese. The Chief Investigator
• Organization: The Prince Charles Hospital

jcroese@bigpond.com

+61733716164

Study Officials

• John Croese, MD

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

  STUDY DIRECTOR

• Dianne Jones, BAppSc

  Logan Hospital

  PRINCIPAL INVESTIGATOR

• Alexander Loukas, PhD

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

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief Investigator

Study Record Dates

• First Submitted: August 6, 2012
• First Posted: August 10, 2012
• Study Start: August 1, 2012
• Primary Completion: March 1, 2014
• Study Completion: March 1, 2014
• Last Updated: October 20, 2014
• Results First Posted: October 13, 2014

Record last verified: 2014-10

Locations

AU (1)