Evidence map›Paper›PMID 33512796›Full record

Trial reportClinical and translational gastroenterology2020

Randomized, Placebo Controlled Trial of Experimental Hookworm Infection for Improving Gluten Tolerance in Celiac Disease.

John Croese, Gregory C Miller, Louise Marquart, Stacey Llewellyn, Rohit Gupta, Luke Becker, Andrew D Clouston, Christine Welch, Julia Sidorenko, Leanne Wallace and 11 more

Open access · goldAbstract readClinical Trial, Phase IMulticenter StudyRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Clinical and translational gastroenterology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed, 2 pooled it
3.4field-weighted citation impact, top 7% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

32 citing papers in PubMed, 2 syntheses or guidelines pooled it, 47 citations in OpenAlex.

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  5. Beyond gluten-free diet: Novel therapeutic frontiers in celiac disease armamentarium.World journal of gastrointestinal pharmacology and therapeutics · 2026
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

21 authors at 8 institutions in 1 country.

John CroeseThe Department of Gastroenterology and Hepatology, The Prince Charles Hospital, Brisbane, Australia.
Gregory C MillerEnvoi Specialist Pathologists, Brisbane, Australia.
Louise MarquartQIMR Berghofer Medical Research Institute, Brisbane, Australia.
Stacey LlewellynQIMR Berghofer Medical Research Institute, Brisbane, Australia.
Rohit GuptaCenter for Molecular Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, Australia.
Luke BeckerCenter for Molecular Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, Australia.
Andrew D CloustonEnvoi Specialist Pathologists, Brisbane, Australia.
Christine WelchDepartment of Gastroenterology, Townsville University Hospital, Townsville, Australia.
Julia SidorenkoInstitute for Molecular Bioscience, The University of Queensland, Brisbane, Australia.
Leanne WallaceInstitute for Molecular Bioscience, The University of Queensland, Brisbane, Australia.
Peter M VisscherInstitute for Molecular Bioscience, The University of Queensland, Brisbane, Australia.
Matthew L RemediosDepartment of Gastroenterology and Hepatology, Royal Brisbane and Women's Hospital, Brisbane, Australia.
James S McCarthyQIMR Berghofer Medical Research Institute, Brisbane, Australia.
Peter O'RourkeQIMR Berghofer Medical Research Institute, Brisbane, Australia.
Graham Radford-SmithQIMR Berghofer Medical Research Institute, Brisbane, Australia.
Alex LoukasCenter for Molecular Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, Australia.
Mark NorrieGastroenterology and Hepatology, Logan Hospital, Brisbane, Australia.
John W MassonDepartment of Gastroenterology, Townsville University Hospital, Townsville, Australia.
Richard B GearryDepartment of Medicine, University of Otago, Christchurch and Canterbury District Health Board, Christchurch, New Zealand.
Tony RahmanThe Department of Gastroenterology and Hepatology, The Prince Charles Hospital, Brisbane, Australia.
Paul R GiacominCenter for Molecular Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, Australia.
QIMR Berghofer Medical Research Institute · AUAustralian Institute of Tropical Health and Medicine · AUJames Cook University · AUThe University of Queensland · AUEnvoi Specialist Pathologists · AUTownsville Hospital · AULogan Hospital · AURoyal Brisbane and Women's Hospital · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionCeliac 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.

methodsWe 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).

resultsSuccessful 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.

Indexed as

AdolescentAdultAgedAged, 80 and overAnimalsCeliac DiseaseDouble-Blind MethodFemaleGlutensHumansLarvaMaleMiddle AgedNecator americanusQuality of LifeTherapy with HelminthsGlutens

Identifiers

PMID33512796
PMCPMC7678792
OpenAlexW3109220664

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.