Desensitising Celiac Disease Patients With the Human Hookworm (NaCeD)

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. Identifier: NCT01661933
Recruitment Status : Completed
First Posted : August 10, 2012
Results First Posted : October 13, 2014
Last Update Posted : October 20, 2014
National Health and Medical Research Council, Australia
Information provided by (Responsible Party):
Dr John Croese, The Prince Charles Hospital

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment;   Masking: Single (Outcomes Assessor);   Primary Purpose: Prevention
Condition: Celiac Disease
Intervention: Biological: Necator americanus

  Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Of 20 potential candidates, 2 could not be contacted (address changed), 1 was not interested, and 5 were unavailable (travel-2, pregnancy-2 or study-1 commitments). Twelve enrolled in September 2012. 8 committed to 3 endoscopic procedures and 2 committed to two endoscopies.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
Necator Americanus, Gluten Challenge Single arm, vertical. Necator americanus: Subjects were inoculated with 20 3rd stage Na larvae (10 + 10 over 4-8 weeks). After hookworm colonization, a micro-dose gluten challenge of 10 mg daily for 6 weeks, followed by 50 mg daily for 6 weeks was completed. After this, a detailed assessment including histology was performed to establish it safe for the participant to proceed to a low-dose gluten challenge of 25 mg daily and 1 G (15-20 G of pasta) twice weekly for 12 weeks. After low-dose challenge, a further evaluation was undertaken before inviting participants to undertake a gluten challenge of 3 G daily over for 2 weeks (preceded by a micro-dose 2 week lead-in).

Participant Flow for 3 periods

Period 1:   Gluten Micro-challenge
    Necator Americanus, Gluten Challenge
STARTED   12 [1] 
COMPLETED   12 [2] 
[1] All 12 enrolled completed hookworm inoculation and gluten micro-challenge.
[2] Two gluten intolerant participants did not proceed to the low-dose challenge.

Period 2:   Low-dose Gluten Challenge
    Necator Americanus, Gluten Challenge
STARTED   12 [1] 
COMPLETED   10 [2] 
Physician Decision                2 
[1] One was symptomatically intolerant to gluten >25 mg. One had active CeD pre- & post-micro-challenge
[2] Two had challenge interrupted for 1-2 weeks. All completed challenge.

Period 3:   High-dose Gluten Challenge
    Necator Americanus, Gluten Challenge
STARTED   10 [1] 
Withdrawal by Subject                2 
[1] 2 of 10 available after post-GC-1g did not enroll for reasons unrelated to gluten.

  Baseline Characteristics

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Mean age 53 years, range 39-67; females 9.

Reporting Groups
Gluten Micro-challenge Single arm, vertical. All twelve healthy adults enrolled subjects were successfully inoculated with hookworm and there was no serious adverse response. Individual hemoglobin levels were all normal and the group mean had significantly increased unexpectedly at completion of the study. Histology was not graded until after low-dose challenge but retrospectively confirmed enrollment Marsh scores of M0-8, M1-1, M2-2 and M3a-1. All participants were complying with a gluten-free diet, were symptomatically well and had a normal anti-tTG.

Baseline Measures
   Gluten Micro-challenge 
Overall Participants Analyzed 
[Units: Participants]
[Units: Participants]
<=18 years   0 
Between 18 and 65 years   11 
>=65 years   1 
[Units: Years]
Mean (Full Range)
 (39 to 67) 
[Units: Participants]
Female   9 
Male   3 

  Outcome Measures

1.  Primary:   Duodenal Villus Height:Crypt Depth   [ Time Frame: Week -24 to -36 ]

2.  Secondary:   Intraepithelial Lymphocyte Count   [ Time Frame: Week-24 and -36 ]

3.  Secondary:   Number of Participants With 2 Points Increase in Marsh Score Post GC-1g   [ Time Frame: Longitudinal change between week-24 and week-36 ]

4.  Secondary:   Serum Anti-tissue Transglutaminase Antibodies Measured as International Units/mL (IU/mL)   [ Time Frame: Anti-tTG IU/mL levels pre-trial, mid-trial and after 3 gram/day gluten challenge ]

  Serious Adverse Events

  Other Adverse Events

  Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
Open study. Small number. Historical controls.

  More Information

Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact:  
Name/Title: Dr John Croese. The Chief Investigator
Organization: The Prince Charles Hospital
phone: +61733716164


Responsible Party: Dr John Croese, The Prince Charles Hospital Identifier: NCT01661933     History of Changes
Other Study ID Numbers: AU/3/BOBD012
First Submitted: August 6, 2012
First Posted: August 10, 2012
Results First Submitted: September 21, 2014
Results First Posted: October 13, 2014
Last Update Posted: October 20, 2014