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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT00671138




Registration number
NCT00671138
Ethics application status
Date submitted
1/05/2008
Date registered
5/05/2008
Date last updated
2/02/2016

Titles & IDs
Public title
Inoculating Celiac Disease Patients With the Human Hookworm Necator Americanus: Evaluating Immunity and Gluten-sensitivity
Scientific 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.
Secondary ID [1] 0 0
IBD-0214R
Secondary ID [2] 0 0
2007/115
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Celiac Disease 0 0
Condition category
Condition code
Inflammatory and Immune System 0 0 0 0
Autoimmune diseases
Oral and Gastrointestinal 0 0 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - Necator americanus
Other interventions - Sham inoculation

Active Comparator: I - Arm I will be inoculated with the human hookworm necator americanus at weeks 0 and 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 interventions: Necator americanus
10 necator americanus larvae will be inoculated at week 0 with a further 5 larvae inoculated at week 12

Other interventions: Sham inoculation
A diluted amount of McIlhenny & Co Tabasco Pepper Sauce will be applied via a gauze dressing at weeks 0 and 12.
Intervention code [1] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Duodenal histology (Marsh classification) and rectal histology
Timepoint [1] 0 0
21 weeks
Secondary outcome [1] 0 0
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.
Timepoint [1] 0 0
21 weeks

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/10/2007
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/09/2009
Sample size
Target
Accrual to date
Final
20
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 0 0
Queensland Institute of Medical Research - Brisbane
Recruitment hospital [2] 0 0
Princess Alexandra Hospital - Brisbane
Recruitment hospital [3] 0 0
Logan Hospital - Logan
Recruitment postcode(s) [1] 0 0
4006 - Brisbane
Recruitment postcode(s) [2] 0 0
4102 - Brisbane
Recruitment postcode(s) [3] 0 0
4131 - Logan

Funding & Sponsors
Primary sponsor type
Other
Name
Princess Alexandra Hospital, Brisbane, Australia
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
The Broad Foundation
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Other
Name [2] 0 0
Townsville Hospital
Address [2] 0 0
Country [2] 0 0
Other collaborator category [3] 0 0
Other
Name [3] 0 0
James Cook University, Queensland, Australia
Address [3] 0 0
Country [3] 0 0
Other collaborator category [4] 0 0
Other
Name [4] 0 0
Walter and Eliza Hall Institute of Medical Research
Address [4] 0 0
Country [4] 0 0
Other collaborator category [5] 0 0
Other
Name [5] 0 0
Queensland Institute of Medical Research
Address [5] 0 0
Country [5] 0 0

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT00671138
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
John T Croese, FRACP MD
Address 0 0
The Townsville Hospital
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT00671138