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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00671138
Recruitment Status : Completed
First Posted : May 5, 2008
Last Update Posted : February 2, 2016
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 (Responsible Party):
A James M Daveson, Princess Alexandra Hospital, Brisbane, Australia

Brief Summary:

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 or disease Intervention/treatment Phase
Celiac Disease Biological: Necator americanus Other: Sham inoculation Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 20 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, 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.
Study Start Date : October 2007
Actual Primary Completion Date : December 2008
Actual Study Completion Date : September 2009

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Celiac Disease

Arm Intervention/treatment
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.

Primary Outcome Measures :
  1. Duodenal histology (Marsh classification) and rectal histology [ Time Frame: 21 weeks ]

Secondary Outcome Measures :
  1. 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 ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00671138

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Australia, Queensland
Queensland Institute of Medical Research
Brisbane, Queensland, Australia, 4006
Princess Alexandra Hospital
Brisbane, Queensland, Australia, 4102
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
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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
Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: A James M Daveson, Doctor, Princess Alexandra Hospital, Brisbane, Australia
ClinicalTrials.gov Identifier: NCT00671138    
Other Study ID Numbers: 2007/115
First Posted: May 5, 2008    Key Record Dates
Last Update Posted: February 2, 2016
Last Verified: January 2016
Keywords provided by A James M Daveson, Princess Alexandra Hospital, Brisbane, Australia:
Celiac disease
Parasitic infections
necator americanus
Additional relevant MeSH terms:
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Celiac Disease
Malabsorption Syndromes
Intestinal Diseases
Gastrointestinal Diseases
Digestive System Diseases
Metabolic Diseases