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Inoculating Celiac Disease Patients With the Human Hookworm Necator Americanus: Evaluating Immunity and Gluten-sensitivity

The recruitment status of this study is unknown because the information has not been verified recently.
Verified January 2009 by Princess Alexandra Hospital, Brisbane, Australia.
Recruitment status was  Active, not recruiting
Sponsor:
Collaborators:
The Broad Foundation
Townsville Hospital
James Cook University, Queensland, Australia
Walter and Eliza Hall Institute of Medical Research
Queensland Institute of Medical Research
Information provided by:
Princess Alexandra Hospital, Brisbane, Australia
ClinicalTrials.gov Identifier:
NCT00671138
First received: May 1, 2008
Last updated: December 8, 2010
Last verified: January 2009
  Purpose

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.


Condition Intervention Phase
Celiac Disease
Biological: Necator americanus
Other: Sham inoculation
Phase 2

Study Type: Interventional
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.

Resource links provided by NLM:


Further study details as provided by Princess Alexandra Hospital, Brisbane, Australia:

Primary Outcome Measures:
  • Duodenal histology (Marsh classification) and rectal histology [ Time Frame: 21 weeks ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • 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 ]

Enrollment: 20
Study Start Date: October 2007
Estimated Study Completion Date: June 2011
Primary Completion Date: December 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diagnosis of celiac disease
  • Positive tTG (IgA)or positive anti IgA gliadin or anti-endomysial antibody test.
  • Marsh score ≥3 on small bowel biopsy (subtotal villous atrophy)
  • Clinical, biochemical or histological improvement on gluten free diet.
  • Compliance with a gluten-free diet for 6 months lead-in.
  • Lifestyle & travel history indicative of a low risk for helminthic infection.
  • Good general health not on immunomodifying agents.
  • Ability to complete study
  • Understand study & risks
  • Social supports
  • Workplace flexibility
  • Normal tTG at enrollment (<10 dependent on serology)
  • A HLA-DQ2 phenotype
  • Negative fecal test for intestinal helminthes.
  • Negative serological test for anti-strongyloides antibodies

Exclusion Criteria:

  • Children (age < 18)
  • Immunomodulating medication in 6 months pre-enrollment
  • Oral or intramuscular/intravascular steroids
  • Regular weekly use of aspirin
  • Regular weekly use of NSAID
  • Regular weekly use of COXII inhibitors
  • Regular weekly use of statin medications
  • Clinical history indicating a likely need to use an immune suppressive agent during the course of the study.
  • Unmanaged risk of pregnancy
  • Past history of infection with helminthes (other than a past history of infection with the pinworm, Enterobius vermicularis)
  • History of insulin dependent diabetes mellitus or Addison's disease
  • History of anaphylaxis or severe allergic reactions
  • Having received a vaccine within the preceding 30 days
  • Positive strongyloides serology
  • Iron deficiency anemia
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00671138

Locations
Australia, Queensland
Princess Alexandra Hospital
Brisbane, Queensland, Australia, 4102
Queensland Institute of Medical Research
Brisbane, Queensland, Australia, 4006
Logan Hospital
Logan, Queensland, Australia, 4131
Sponsors and Collaborators
Princess Alexandra Hospital, Brisbane, Australia
The Broad Foundation
Townsville Hospital
James Cook University, Queensland, Australia
Walter and Eliza Hall Institute of Medical Research
Queensland Institute of Medical Research
Investigators
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
  More Information

Additional Information:
No publications provided by Princess Alexandra Hospital, Brisbane, Australia

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Dr John Croese, Princess Alexandra Hospital
ClinicalTrials.gov Identifier: NCT00671138     History of Changes
Other Study ID Numbers: 2007/115, IBD-0214R
Study First Received: May 1, 2008
Last Updated: December 8, 2010
Health Authority: Australia: Department of Health and Ageing Therapeutic Goods Administration

Keywords provided by Princess Alexandra Hospital, Brisbane, Australia:
Celiac disease
Parasitic infections
necator americanus
Immunity

Additional relevant MeSH terms:
Celiac Disease
Digestive System Diseases
Gastrointestinal Diseases
Intestinal Diseases
Malabsorption Syndromes
Metabolic Diseases

ClinicalTrials.gov processed this record on November 20, 2014