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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/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]

IBD-0214R

Secondary ID [2]

2007/115

Universal Trial Number (UTN)

Trial acronym

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Celiac Disease

Condition category

Condition code

Inflammatory and Immune System

Autoimmune diseases

Oral and Gastrointestinal

Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon

Human Genetics and Inherited Disorders

Other human genetics and inherited disorders

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

Treatment: Other - 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®

Treatment: Other: 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]

Treatment: Other

Intervention code [2]

Other interventions

Comparator / control treatment

Control group

Outcomes

Primary outcome [1]

Duodenal histology (Marsh classification) and rectal histology

Timepoint [1]

21 weeks

Secondary outcome [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.

Timepoint [1]

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?

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

Recruitment in Australia

Recruitment state(s)

QLD

Recruitment hospital [1]

Queensland Institute of Medical Research - Brisbane

Recruitment hospital [2]

Princess Alexandra Hospital - Brisbane

Recruitment hospital [3]

Logan Hospital - Logan

Recruitment postcode(s) [1]

4006 - Brisbane

Recruitment postcode(s) [2]

4102 - Brisbane

Recruitment postcode(s) [3]

4131 - Logan

Funding & Sponsors

Primary sponsor type

Other

Name

Princess Alexandra Hospital, Brisbane, Australia

Address

Country

Other collaborator category [1]

Other

Name [1]

The Broad Foundation

Address [1]

Country [1]

Other collaborator category [2]

Government body

Name [2]

Townsville Hospital

Address [2]

Country [2]

Other collaborator category [3]

Other

Name [3]

James Cook University, Queensland, Australia

Address [3]

Country [3]

Other collaborator category [4]

Other

Name [4]

Walter and Eliza Hall Institute of Medical Research

Address [4]

Country [4]

Other collaborator category [5]

Other

Name [5]

Queensland Institute of Medical Research

Address [5]

Country [5]

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/study/NCT00671138

Trial related presentations / publications

Cantacessi C, Giacomin P, Croese J, Zakrzewski M, Sotillo J, McCann L, Nolan MJ, Mitreva M, Krause L, Loukas A. Impact of experimental hookworm infection on the human gut microbiota. J Infect Dis. 2014 Nov 1;210(9):1431-4. doi: 10.1093/infdis/jiu256. Epub 2014 May 3.
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.

Public notes

Contacts

Principal investigator

Name

John T Croese, FRACP MD

Address

The Townsville Hospital

Country

Phone

Fax

Contact person for public queries

Name

Address

Country

Phone

Fax

Contact person for scientific queries

No information has been provided regarding IPD availability

What supporting documents are/will be available?

No Supporting Document Provided

Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results not provided in https://clinicaltrials.gov/study/NCT00671138

Trial Review

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