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Desensitising Celiac Disease Patients With the Human Hookworm (NaCeD)

This study has been completed.
Sponsor:
Collaborator:
National Health and Medical Research Council, Australia
Information provided by (Responsible Party):
Dr John Croese, The Prince Charles Hospital
ClinicalTrials.gov Identifier:
NCT01661933
First received: August 6, 2012
Last updated: October 10, 2014
Last verified: October 2014
Results First Received: September 21, 2014  
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
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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
  Description
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] 
NOT COMPLETED   0 
[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] 
NOT COMPLETED   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] 
COMPLETED   8 
NOT COMPLETED   2 
Withdrawal by Subject                2 
[1] 2 of 10 available after post-GC-1g did not enroll for reasons unrelated to gluten.



  Baseline Characteristics
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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
  Description
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]
 12 
Age 
[Units: Participants]
 
<=18 years   0 
Between 18 and 65 years   11 
>=65 years   1 
Age 
[Units: Years]
Mean (Full Range)
 53 
 (39 to 67) 
Gender 
[Units: Participants]
 
Female   9 
Male   3 


  Outcome Measures
  Show All 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
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Time Frame No text entered.
Additional Description No text entered.

Frequency Threshold
Threshold above which other adverse events are reported   0%  

Reporting Groups
  Description
Gluten Micro-challenge Single arm, longitudinal study of responses to escalating gluten doses in people with celiac disease after infection with Necator americanus, a human hookworm.

Other Adverse Events
    Gluten Micro-challenge
Total, Other (not including serious) Adverse Events   
# participants affected / at risk   2/12 (16.67%) 
Gastrointestinal disorders   
Symptomatic gluten intolerance † [3]   
# participants affected / at risk   1/12 (8.33%) 
# events   1 
Active CeD * [4]   
# participants affected / at risk   1/12 (8.33%) 
# events   1 
Events were collected by systematic assessment
* Events were collected by non-systematic assessment
[3] One subject experienced nausea and pain when gluten doses exceeded 25 mg/d and was advised not to continue.
[4] One subject had Marsh 3a inflammation on biopsy collected immediately post-micro-challenge. Retrospective analysis established that this was likely present immediately pre-trial.



  Limitations and Caveats
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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
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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
e-mail: jcroese@bigpond.com


Publications:

Responsible Party: Dr John Croese, The Prince Charles Hospital
ClinicalTrials.gov Identifier: NCT01661933     History of Changes
Other Study ID Numbers: AU/3/BOBD012
Study First Received: August 6, 2012
Results First Received: September 21, 2014
Last Updated: October 10, 2014