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Helminth therapy (worms) for induction of remission in inflammatory bowel disease

  1. Sushil K Garg1,*,
  2. Ashley M Croft2,
  3. Peter Bager3

Editorial Group: Cochrane IBD Group

Published Online: 20 JAN 2014

Assessed as up-to-date: 13 JUL 2013

DOI: 10.1002/14651858.CD009400.pub2


How to Cite

Garg SK, Croft AM, Bager P. Helminth therapy (worms) for induction of remission in inflammatory bowel disease. Cochrane Database of Systematic Reviews 2014, Issue 1. Art. No.: CD009400. DOI: 10.1002/14651858.CD009400.pub2.

Author Information

  1. 1

    University of Minnesota, Department of Surgery, Minneapolis, MN, USA

  2. 2

    Ministry of Defence, Surgeon General's Department, London, UK

  3. 3

    Statens Serum Institut, Department of Epidemiology Research, Copenhagen, Denmark

*Sushil K Garg, Department of Surgery, University of Minnesota, 420 Delaware Street SE, Mayo Mail Code 195, Minneapolis, MN, 55455, USA. sushilaiims@gmail.com. kumar154@umn.edu.

Publication History

  1. Publication Status: New
  2. Published Online: 20 JAN 2014

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Characteristics of included studies [ordered by study ID]
Sandborn 2013

MethodsRandomised, double blind, placebo-controlled, parallel group trial

Clinical and laboratory examinations were performed at entry, 2 weeks and 6 months


ParticipantsAdult patients (18 to 55 years) with a confirmed diagnosis of Crohn's disease by established criteria with a minimum duration of 3 months were recruited from were recruited from 6 investigational centres in US


InterventionsA single treatment of Trichuris suis ova at doses of 500 (n = 9), 2500 (n = 9) or 7500 (n = 9) embryonated viable T. suis ova or matching placebo (n = 9)


OutcomesAdverse events

Patient diary card


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low risk"The randomisation was generated by the drug packaging vendor using a software algorithm that allocated patients to each treatment according to the study design specifications"

Allocation concealment (selection bias)Low riskCentralized allocation by the drug packaging vendor

Blinding of participants and personnel (performance bias)
All outcomes
Low riskMatching placebo

Blinding of outcome assessment (detection bias)
All outcomes
Low riskMatching placebo

Incomplete outcome data (attrition bias)
All outcomes
Low riskPatient withdrawal was equal in all groups

Selective reporting (reporting bias)Low riskThe published report included all expected outcomes

Other biasLow riskThe study appears to be free of other sources of bias

Summers 2005a

MethodsRandomised, double blind, placebo-controlled, parallel group trial

Clinical and laboratory examinations were performed at recruitment, and weeks 2, 4 and 8


ParticipantsAdult patients (18 to 72 years) with active ulcerative colitis (defined by a UCDAI score of > 4) were recruited from the University of Iowa's Center for Digestive Diseases and select gastroenterology practices in the State of Iowa (N = 54)


InterventionsAll patients received 2500 Trichuris suis ova (n = 30) or placebo (n = 24) orally at 2 week intervals for 12 weeks


OutcomesClinical improvement at 12 weeks (defined as a decrease in the UCDAI of more than 3 from baseline) was the primary measure of efficacy

Clinical remission, as defined by UCDAI of less than 3, was a secondary end point


NotesThe sponsors did not take part in and in no way influenced the research design,data collection, data analyses, interpretation of the data, or preparation and approval of the manuscript


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low risk"This individual, an experienced nurse investigator, assigned participants to receive ova or placebo by using a set of random numbers that was selected at the time of enrolment".

Allocation concealment (selection bias)Low riskCentralised randomisation by nurse investigator

"An individual not involved in the study and who had no patient contact prepared and coded all vials"

Blinding of participants and personnel (performance bias)
All outcomes
Low risk"The placebo and active treatment vials were indistinguishable"

Blinding of outcome assessment (detection bias)
All outcomes
Low riskAlthough blinding of outcomes assessment was not clearly described we believe outcome assessors were blind due to the indistinguishable placebo

Incomplete outcome data (attrition bias)
All outcomes
Low riskOne patient in each group discontinued treatment

Selective reporting (reporting bias)Low riskThe published report included all expected outcomes

Other biasLow riskThe study appears to be free of other sources of bias

 
Characteristics of excluded studies [ordered by study ID]

StudyReason for exclusion

Croese 2006Not a RCT

Summers 2003Not a RCT

Summers 2005bNot a RCT

 
Characteristics of ongoing studies [ordered by study ID]
NCT01279577

Trial name or titleTrichuris suis ova (TSO) suspension versus placebo in active Crohn's disease

MethodsRandomised, double-blind, placebo-controlled, multi-centre phase II study

ParticipantsAdult patients (18 to 75 years) with an established diagnosis of Crohn's disease of at least 3 months duration prior to screening

InterventionsDifferent doses of Trichuris suis ova (defined as low, medium and high dose) or placebo

OutcomesPrimary Outcome: rate of clinical remission at week 12 (LOCF) defined as a CDAI < 150
Secondary Outcomes: reduction of > 100 points in CDAI from baseline at week 12 and adverse events

Starting dateNovember 2010

Contact informationDr Ralph Müller

Notes

NCT01434693

Trial name or titleA sequential dose-escalation, double-blind, placebo-controlled, phase I study to evaluate the safety and tolerability of single doses of 3 different doses of oral CNDO-201 Trichuris suis ova suspension (Tso) in patients with Crohn's disease

MethodsRandomised, double-blind, placebo-controlled, multi-centre phase I study

ParticipantsAdult patients (18 to 55 years) with a confirmed diagnosis of Crohn's disease with a minimum disease duration of 3 months

InterventionsTSO 500

TSO 2500

TSO 7500

Placebo

OutcomesIncidence of adverse events with a specific focus on reported gastrointestinal signs and symptoms (6 month follow-up)

Starting dateSeptember 2011

Contact informationCoronado Biosciences, Inc

Notes

 
Comparison 1. Trichuris suis eggs versus placebo

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Clinical remission (UCDAI < 3)1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

 2 Clinical improvement (decrease in UCDAI of > 3)1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

 3 UCDAI at 12 weeks1Mean Difference (IV, Fixed, 95% CI)Totals not selected

 4 Adverse events2Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

    4.1 Ulcerative colitis
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

    4.2 Crohn's disease
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

 5 Study withdrawal2Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

    5.1 Ulcerative colitis
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

    5.2 Crohn's disease
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

 
Summary of findings for the main comparison. Trichuris suis eggs versus placebo for induction of remission in ulcerative colitis

Trichuris suis eggs versus placebo for induction of remission in ulcerative colitis

Patient or population: induction of remission in ulcerative colitis
Settings: Outpatient
Intervention: Trichuris suis eggs versus placebo

OutcomesIllustrative comparative risks* (95% CI)Relative effect
(95% CI)
No of Participants
(studies)
Quality of the evidence
(GRADE)
Comments

Assumed riskCorresponding risk

ControlTrichuris suis eggs versus placebo

Clinical remission
Follow-up: 12 weeks
42 per 10001100 per 1000
(11 to 533)
RR 2.40 (0.27 to 21.63)54
(1 study)
⊕⊕⊝⊝
Low2

Clinical improvement at 12 weeks
Follow-up: 12 weeks
167 per 10001434 per 1000

(162 to 1161)
RR 2.60 (0.97 to 6.95)54
(1 study)
⊕⊕⊝⊝
Low3

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: Confidence interval; RR: Risk ratio

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

 1 The control group risk estimate comes from the control arm of the included study.
2 There is serious imprecision as there are relatively few events (4 events) and wide confidence interval around estimate of effect.
3 There is serious imprecision as there are relatively few events (17 events) and wide confidence interval around estimate of effect.