Inoculating Celiac Disease Patients With the Human Hookworm Necator Americanus: Evaluating Immunity and Gluten-sensitivity
Recruitment status was Active, not recruiting
The disappearance of intestinal parasites from humans in developed countries may be responsible for the upsurge in many diseases including Celiac Disease, Crohn's, ulcerative colitis, asthma and hay fever. A parasite's survival relies on its ability to interfere with the host's immune response. The mechanisms employed to do this are similar to those required by a person to regulate against the so-called autoimmune disorders, diseases in which the system turns on itself. The investigators suspect that when parasites are excluded from the environment, some individuals become sufficiently self-reactive to develop an autoimmune disease. American researchers have successfully treated patients with Crohn's and ulcerative colitis using a pig whipworm (Trichuris suis). The investigators have undertaken a similar preliminary study using a human hookworm in Crohn's patients.
Using a small group of healthy people with celiac disease, the investigators will test if a human hookworm, Necator americanus, inhibits immune responsiveness to gluten. Celiac disease is a very common autoimmune-like disease (1% of Americans are affected although only a minority are aware they have the condition). In this condition, an individual becomes reactive to gluten, a protein in foods derived from wheat, barley, oats and rye.
What makes celiac disease such a good model for Crohn's disease is that similar immune changes are common to both, but in celiac disease the people are usually well, are not taking powerful immune suppressive drugs and the provocative antigens (the molecules that engage the immune system and provoke the disease) are known and can be excluded or introduced. As well as being of direct benefit to people with celiac disease, this study may give direction as to the potential of this parasite to manage inflammatory bowel disease.
People with proven celiac disease who live in Brisbane, a modern Australian city, will be invited to participate. Enrollment will require that the candidate has been avoiding gluten for six months.
The study is a blinded study (where the researchers and study subjects do not know who has gotten the parasites) aimed at comparing the disease activity and immunity after a controlled breach of the gluten-free diet in individuals with celiac disease, before and after hookworm infection. The disease severity and the immune system of celiac subjects before and after being inoculated with N. americanus will be examined using conventional and experimental investigations. This group's immunity will be compared to that of a group of matched, celiac control subjects (not infected with hookworm), before and after eating four pieces of standard white bread each day for three to five days. Twenty people, ten subjects per arm, will be recruited. Ten larvae initially, then five more after twelve weeks will be placed on the skin under a light dressing for thirty minutes.
The investigators aim to test whether the hookworm infection will change the immune processes and suppress gluten sensitivity in people with celiac disease. Outcomes to be measured will be those that reflect the activity of celiac disease.
Biological: Necator americanus
Other: Sham inoculation
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||A Phase 2a, Randomized, Double Blinded, Placebo Controlled, Study Evaluating Immunity and Gluten-sensitivity by Inoculating Celiac Disease Patients With the Human Hookworm Necator Americanus.|
- Duodenal histology (Marsh classification) and rectal histology [ Time Frame: 21 weeks ] [ Designated as safety issue: Yes ]
- Peripheral blood mononuclear cells and mucosal lymphocytes will be grown ex vivo and challenged with gluten antigen immunodominant peptide. Cell proliferation and cytokine profiles will also be measured. [ Time Frame: 21 weeks ] [ Designated as safety issue: No ]
|Study Start Date:||October 2007|
|Estimated Study Completion Date:||June 2011|
|Primary Completion Date:||December 2008 (Final data collection date for primary outcome measure)|
Active Comparator: I
Arm I will be inoculated with the human hookworm necator americanus at weeks 0 and 12.
Biological: Necator americanus
10 necator americanus larvae will be inoculated at week 0 with a further 5 larvae inoculated at week 12
Placebo Comparator: II
Arm II participants will receive and identical sham-inoculums comprising a diluted amount of 0.2ml McIlhenny & Co Tabasco Pepper Sauce®
Other: Sham inoculation
A diluted amount of McIlhenny & Co Tabasco Pepper Sauce will be applied via a gauze dressing at weeks 0 and 12.
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|Princess Alexandra Hospital|
|Brisbane, Queensland, Australia, 4102|
|Queensland Institute of Medical Research|
|Brisbane, Queensland, Australia, 4006|
|Logan, Queensland, Australia, 4131|
|Principal Investigator:||John T Croese, FRACP MD||The Townsville Hospital|
|Study Director:||A James M Daveson, MBBS||Princess Alexandra Hospital|
|Study Director:||Alex Loukas, BSc Hon, PhD (UQ)||Queensland Institute of Medical Research|
|Study Director:||James McCarthy, MBBS FRACP PhD||Queensland Institute of Medical Research|
|Study Director:||Robert Anderson, MB ChB BMedSc PhD FRACP||Walter & Eliza Hall Institute of Immunology|
|Study Director:||Graeme Macdonald, MBBS FRACP PhD||Princess Alexandra Hospital|
|Study Director:||Soraya Gaze, BSc PhD||Queensland Institute of Medical Research|
|Study Director:||Rick Speares, MBBS PhD||Anton Breinl Centre for Public Health and Tropical Medicine, James Cook University, Townsville|
|Study Director:||Andrew Clouston, MBBS (Qld) PhD (Qld) FRCPA||Envoi Pathology|
|Study Director:||Andrew Pascoe, B. Pharm, B.Sc, MBBS, FRACP||Princess Alexandra Hospital|
|Study Director:||Geoffrey Cobert, BSc PhD||Queensland Institute of Medical Research|
|Study Director:||Dianne Jones, RN RM BAppSc||Princess Alexandra Hospital|
|Study Director:||Sharon Cooke, RN||The Townsville Hospital|