Worms for Immune Regulation of Multiple Sclerosis
Condition: Multiple Sclerosis, Relapsing-Remitting
MeSH terms: Multiple Sclerosis; Multiple Sclerosis, Relapsing-Remitting; Sclerosis
Study type: Interventional
Phase: Phase 2

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.
    

Intervention name(s): Hookworm larvae; Placebo
Intervention type(s): Biological; Biological
Intervention description(s): 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.; 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.
Other intervention name(s): Necator americanus; Water
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Multiple sclerosis; Hookworm larvae; Necator americanus; Treg cells