Clinical trial NCT00469989: Randomised Placebo Controlled Study of Effects of Therapeutic Hookworm Infection in Asthma
Official title: Randomised Placebo Controlled Study of Effects of Therapeutic Hookworm Infection in Asthma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Asthma
Keywords: immune system
allergy
hookworm infection
parasite infection
asthma
Lead sponsor: University of Nottingham
Sponsor class: OTHER
First posted: 2007-05-07
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: There has been considerable debate over the last 30 years about the interaction between asthma and parasitic infection. It has been suggested that at least part of the reason for the increasing prevalence of asthma in the developed world is a decrease in parasite infections resulting from improved living conditions with economic development. Our previous studies in Ethiopia suggest that hookworm infection may be particularly important in this process.

To establish definitively whether parasites can protect against allergic disease, and specifically asthma, ultimately requires a randomised clinical trial of parasite infection in patients with asthma. We, the researchers at the University of Nottingham, have completed a study in normal volunteers to establish the dose of hookworms necessary to generate infection at the level shown to be protective in population surveys, and shown that infection is well tolerated. In addition, we have recently completed a randomized placebo-controlled clinical trial of hookworm infection in allergic patients with rhinitis which showed that there was no negative effect on bronchial responsiveness during the phase in the lifecycle where the hookworm larvae migrate through the lungs. Consequently, are now proceeding with the definitive randomized placebo-controlled trial of hookworm infection in people with asthma. This study will also provide us with the opportunity to investigate the cellular mechanisms of the effect of hookworm infection on the immune system.

Detailed description: Epidemiological evidence suggests that human hookworm infection is associated with a reduced risk of asthma and allergic disease. This association is potentially important not only to understanding the aetiology of asthma and allergic disease, but also because it suggests that hookworms or their products might be therapeutically effective in these conditions. To test the hypothesis that hookworms protect against asthma ultimately requires a clinical trial.

We have carried out a dose-ranging study to establish the dose of hookworm larvae necessary to generate infection at the intensity shown to be protective in epidemiological studies, with acceptable side effects. We have also completed a randomized controlled clinical trial of hookworm infection in people with allergic rhinoconjunctivitis and have shown that there is no significant change in airway responsiveness during the lung migration phase of the hookworm life cycle. We are now performing the definitive study which is a randomized placebo-controlled trial of the effects of therapeutic hookworm infection in people with asthma. During this study, we will be monitoring various indicators of asthma control but will also be able to measure a range of relevant immunological parameters to explore the relation between these parameters and expression of the allergic and asthmatic phenotypes

Eligibility criteria: Inclusion Criteria:

* Clinical diagnosis of asthma
* Use of regular inhaled corticosteroid treatment to a maximum of 1000mcg beclomethasone or equivalent per day
* Measurable airway responsiveness to AMP
* Negative hookworm serology
* Positive skin prick tests to D.pteronyssinum, cat fur or grass pollen

Exclusion Criteria:

* Possible or planned pregnancy or breastfeeding
* Use of regular oral corticosteroids or immunosuppressive medication
* Anemia
* History of anaphylaxis

Primary outcomes:
measure: Change from baseline airway responsiveness to adenosine-5-monophosphate (AMP) during the 12 weeks of the study.
Secondary outcomes:
measure: Change in peak flow variability, asthma symptom scores, asthma medication usage, allergen skin wheal response,total and specific IgE titres, acidic mammalian chitinase, cytokine profiles, other inflammatory markers
measure: occurrence of adverse effects.
Other outcomes:
Locations:
city: Nottingham
country: United Kingdom
facility: University of Nottingham
Study officials:
affiliation: University of Nottingham
name: John Britton
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Nottingham
name: David Pritchard
role: PRINCIPAL_INVESTIGATOR
References: