NCT01470521

Worms for Immune Regulation of Multiple Sclerosis

Worms for Immune Regulation of Multiple Sclerosis (WIRMS)

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 72 (actual)
• Sponsor: University of Nottingham · Academic / Other
• Sex: All
• Age: 18 Years – 65 Years
• Healthy volunteers: Not accepted

Summary

The purpose of this study is to determine whether people with MS who are exposed to a small number of hookworms will have less inflammation and less MS disease activity.

Detailed description

There is evidence that certain parasitic infections may protect against autoimmune or inflammatory diseases, including multiple sclerosis (MS), asthma and type1 diabetes. The 'hygiene hypothesis' postulates exposure to infectious agents confers protection against these disorders. One putative mechanism depends on the activity of regulatory T cells (Treg), naturally occurring or induced cells that prevent excessive immune activation and autoimmunity. Reports in the last 5 years lend credence to the hygiene hypothesis in MS: epidemiological investigations show an inverse relationship to infections with the nematode Trichuris, and a study with serial clinical, immunological and MRI follow-up shows MS patients developing intestinal parasitoses have much milder disease course compared with uninfected matched MS controls followed over 5 years. A role for Treg and also a novel population of B regulatory (Breg) cells is suggested in this study. The University of Nottingham has extensive experience with human parasite research and have completed essential safety studies of controlled infection with hookworm in normal volunteers and people with atopy. Asthma and Crohn's disease studies are underway and show an immunological effect even with 10 larvae. This is the first controlled parasite exposure study in patients with relapsing MS with in 36 patients 25 hookworm larvae vs 36 patients with placebo. Patients will be followed clinically (relapse rate, disability scores), immunologically and radiologically (serial MRI scans with Gadolinium) for 1 year. The cumulative number of new and active lesions on T2 weighted MRI will be the primary outcome measure. Regulatory network induction (Treg induction, Breg/Tr1 and NK) will be the immunological secondary outcome measure. Relapse rate will be secondary clinical outcome measure. A number of clinical, MRI and immune parameters will be exploratory measures. Cytokine profiles, eosinophil and egg counts, IgE and IgG subsets and IgE/IgG4 ratios will be measured, to relate altered immune responses to disease modulation. Immune responses will be assessed to neuroantigen and to mitogen, and parasite antigens (excretory/secretory products). This study will be an essential early step in assessing the potential for therapeutic immunomodulation with parasites in MS.

Conditions

• Multiple Sclerosis, Relapsing-Remitting

Interventions

Type	Name	Description
BIOLOGICAL	Hookworm larvae	Hookworm larvae solution is pipetted onto a plaster dressing which is then placed on the upper forearm for 24 hours. This is administered only once.
BIOLOGICAL	Placebo	Pharmacopoeial grade water is pipetted onto a plaster dressing which is then placed on the upper forearm for 24 hours. This is administered only once.

Timeline

• Start date: 2011-12-01
• Primary completion: 2016-01-01
• Completion: 2016-01-01
• First posted: 2011-11-11
• Last updated: 2016-01-29

Locations

1 site across 1 country: United Kingdom