Randomized, placebo controlled trial of experimental hookworm infection for improving gluten tolerance in Celiac disease

Croese, John, Miller, Gregory C., Marquart, Louise, Llewellyn, Stacey, Gupta, Rohit, Becker, Luke, Clouston, Andrew D., Welch, Christine, Sidorenko, Julia, Wallace, Leanne, Visscher, Peter M., Remedios, Matthew L., McCarthy, James S., O'Rourke, Peter, Radford-Smith, Graham, Loukas, Alex, Norrie, Mark, Masson, John W., Gearry, Richard B., Rahman, Tony, and Giacomin, Paul (2020) Randomized, placebo controlled trial of experimental hookworm infection for improving gluten tolerance in Celiac disease. Clinical and Translational Gastroenterology, 11. e00274.

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Abstract

INTRODUCTION: Celiac disease is an autoimmune disorder where intestinal immunopathology arises after gluten consumption. Previous studies suggested that hookworm infection restores gluten tolerance; however, these studies were small (n = 12) and not placebo controlled.

METHODS: We undertook a randomized, placebo-controlled trial of hookworm infection in 54 people with celiac disease. The 94-week study involved treatment with either 20 or 40 Necator americanus third-stage larvae (L3-20 or L3-40) or placebo, followed by escalating gluten consumption (50 mg/d for 12 weeks, 1 g intermittent twice weekly for 12 weeks, 2 g/d sustained for 6 weeks, liberal diet for 1 year).

RESULTS: Successful study completion rates at week 42 (primary outcome) were similar in each group (placebo: 57%, L3-20: 37%, and L3-40: 44%; P = 0.61), however gluten-related adverse events were significantly reduced in hookworm-treated participants: Median (range) adverse events/participant were as follows: placebo, 4 (1–9); L3-20, 1 (0–9); and L3-40, 0 (0–3) (P = 0.019). Duodenal villous height:crypt depth deteriorated similarly compared with their enrolment values in each group (mean change [95% confidence interval]: placebo, −0.6 [−1.3 to 0.2]; L3-20, −0.5 [−0.8 to 0.2]; and L3-40, −1.1 [−1.8 to 0.4]; P = 0.12). A retrospective analysis revealed that 9 of the 40 L3-treated participants failed to establish hookworm infections. Although week 42 completion rates were similar in hookworm-positive vs hookworm-negative participants (48% vs 44%, P = 0.43), quality of life symptom scores were lower in hookworm-positive participants after intermittent gluten challenge (mean [95% confidence interval]: 38.9 [33.9–44] vs 45.9 [39.2–52.6]).

DISCUSSION: Hookworm infection does not restore tolerance to sustained moderate consumption of gluten (2 g/d) but was associated with improved symptom scores after intermittent consumption of lower, intermittent gluten doses.

Item ID: 67561
Item Type: Article (Research - C1)
ISSN: 2155-384X
Copyright Information: © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology. s This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.
Funders: Australian National Health and Medical Research Council (NHMRC), Advance Queensland Fellowship (AQF), The Prince Charles Hospital Foundation, Celiac Australia, Bowel and Liver Trust, NZ Lottery Health Research Fund, Australian Institute of Tropical Health and Medicine (AITHM), Australian Research Council (ARC)
Projects and Grants: NHMRC Project Grant, NHMRC Senior Principal Research Fellowship, NHMRC Practitioner Fellowship
Date Deposited: 25 May 2021 04:31
FoR Codes: 32 BIOMEDICAL AND CLINICAL SCIENCES > 3207 Medical microbiology > 320704 Medical parasitology @ 100%
SEO Codes: 20 HEALTH > 2001 Clinical health > 200104 Prevention of human diseases and conditions @ 100%
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