Lay Summary

Proposal No. IBD-0184
Principal Investigator:   Paul J. Fortun, BM BCh
Applicant Organization:  University of Nottingham (United Kingdom)
Project Title: Hookworm infestation as therapy in Crohn's disease
Period of Award:  August 14, 2006 – August 13, 2008

Hookworms are small worms that live in the intestine of hundreds of millions of people in the world. In most cases, a person would not know they have hookworm because light infections cause few symptoms, and the person and the worm live in relative harmony for years. The worm induces this state of tolerance by calming the inflammatory responses of the bowel, perhaps by releasing anti-inflammatory chemicals. In theory, this should reduce the activity of CD, leading to a reduction in symptoms. There is quite a lot of evidence that this might occur. In countries where hookworm is common, Crohn’s disease is very uncommon.

We have shown in preliminary studies that infection with just ten hookworms has a significant effect on inflammatory processes and is well tolerated. Hookworms have been successfully given to patients with Crohn’s disease and there is some case report evidence that those with active disease experience a reduction in activity.

We would like to investigate under rigorous clinical trial conditions whether hookworm can reduce disease activity and symptoms in people with mild to moderately active Crohn’s disease.  People who take part would be randomized to receive ten hookworm larvae or a placebo (inactive treatment).  This would be administered under a sticking plaster. The tiny larvae make their way through the skin eventually into the intestine (after about three weeks).  This is when benefits of infection might be expected.  Patients whose symptoms of Crohn’s disease are severe enough to warrant it are allowed to take a short course of steroids to control disease activity before this time if necessary.  Treatment is assessed in terms of symptoms after 12 weeks and the hookworm will then be eradicated with tablets. There will be a further visit 12 weeks later.

Although some patients might want us not to eradicate their hookworms, because of improvement, it is important to proceed cautiously. However as experience grows, and for patients who derive clinical benefit from hookworm, there may well be an option to undergo further long-term treatment later. In addition, the research will help us to identify what it is in hookworms that have such a powerful effect on inflammation and that might be the basis for future drug development for Crohn’s disease.