Immunoregulation by Controlled Parasite Exposure in Multiple Sclerosis. (WIRMS-1)

June 13, 2012 updated by: University of Nottingham
The aim of the study is to determine whether controlled infection with a clinically safe number of larvae of hookworm results in an immune response that is protective in relapsing MS.

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

Detailed Description

Studies have shown that there may be an inverse relationship between infections with worms including hookworms and inflammatory diseases including multiple sclerosis (MS). This has been explained by a protective immune reaction that is triggered by the hookworm in the body that dampens inflammation. In mice with MS, infections with some mouse worms reduced the inflammation and damage to their brain. The primary purpose of this study is to determine whether people with MS who are exposed to a small number of hookworms will develop this protective immune reaction that may reduce MS disease activity. We also plan to determine the effect of the hookworms on relapses during 1 year study.

A study of people with MS naturally infected with intestinal parasites did show significant protection over 5 years, and the levels of biological markers of the infection and some immune substances triggered by it were similar to the ones we obtained with controlled infection in normal volunteers, allergic and asthmatic peoples. We think the study has a genuine potential to benefit people with MS, and there is known interest in the MS patient community. At the therapeutic doses proposed here, this is an innocuous infection. Natural hookworm infection affects 1 billion people worldwide, often without symptoms unless the parasite load is very high. Our controlled exposure studies have shown good tolerability and safety; the risk of infecting others and auto-infection virtually is nil in Western standard hygiene conditions. Many people with MS when asked stated they would prefer an innocuous infection with microscopic larvae to a man-made product that may have more side effects. If the protective mechanisms are determined these studies may also lead to new ways of treating MS, possibly by selecting only the specific chemical components of the worms and the immune response to them that confer protection.

The increase in MS in the Western world, along with other autoimmune inflammatory diseases and asthma may be attributed to decreased exposure to infections such as gut parasites due to improved hygiene ('the hygiene hypothesis'). In animal models, controlled parasite infections including hookworms and related worms protect against MS-like disease. Parasites have evolved host-specific molecular mechanisms to dampen or condition the excessive immune responses against them and thus survive. These parasites induce regulatory mechanisms including Treg and a novel class of B cells that also dampen immune responses called Breg and were recently shown to improve MS in natural infection. They may suppress a class of lymphocytes that cause most damage in MS, Th17 cells. We will produce, with controlled exposure, a similar response to those associated with protective natural exposure in MS. We have the unique combination of expertise in hookworm biology, controlled parasite exposure and immunology of MS and MS trials and our data from our other human studies indicate this is a safe and tolerable intervention of significant potential.

Study Type

Interventional

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United Kingdom
    • Nottinghamshire
      • Nottingham, Nottinghamshire, United Kingdom, NG7 2UH
        • Nottingham University Hospital NHS Trust

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 60 years (ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Patients with documented multiple sclerosis relapsing remitting or secondary progressive with relapses, according to McDonald's criteria, and an MRI scan consistent with MS according to Fazekas criteria
  2. Patients with at least 1 relapse in the last 12 months
  3. Patients with EDSS score in the range of 0 to 5.5 at the baseline visit
  4. Patients of both genders, age >18 years and < 60 years
  5. Women of child bearing potential, (who have a negative pregnancy test) must agree to use methods of medically acceptable forms of contraception during the study.
  6. Be able and willing to comply with study visits and procedures per protocol.
  7. Understand, sign, and date the written voluntary informed consent form at the screening visit prior to any protocol-specific procedures performed.

Exclusion Criteria:

No populations at risk of severe illness or death will be included in this study

  1. Life expectancy < 6 months.
  2. Patient is < 5 years free of malignancy, except treated basal cell skin cancer or cervical carcinoma in situ.
  3. Patient with grade III/IV cardiac problems as defined by the New York Heart Association Criteria. (i.e., congestive heart failure, myocardial infarction within 6 months of study)
  4. Patients with severe and/or uncontrolled medical condition.
  5. Patient has a known diagnosis of human immunodeficiency virus (HIV) infection.
  6. Anaemia (Hb <10 g/dL for females, <11 g/dL for males)
  7. Prior or present evidence of parasitic infection; prior treatment with anti-helminthic drugs
  8. Patient with serious medical or psychiatric illness that could potentially interfere with the completion of the study treatment according to this protocol
  9. History of poor compliance or history of drug/alcohol abuse, or excessive alcohol consumption that would interfere with the ability to comply with the study protocol,
  10. Severe asthma, allergy, other autoimmune disease or any condition that the physician judges could be detrimental to subjects participating in this study; including deviations deemed clinically important from normal clinical laboratory

Previous treatment

  1. Treatment with interferon or glatiramer acetate or immunosuppressive drugs within 26 weeks prior to baseline
  2. Treatment with bone marrow transplantation, total lymphoid irradiation, monoclonal antibodies, umbilical cord stem cells, AIMSPRO at any time prior to baseline
  3. Treatment with corticosteroids or ACTH within 4 weeks prior to baseline
  4. Treatment with any investigational agent within 12 weeks prior to baseline

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: QUADRUPLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 1
Patients will receive 25 live hookworm larvae.
Biological: Live Hookworm Larvae
25 live hookworm will be applied to the arm and will infect transdermally. They will be eradicated after 48 weeks.
Other Names:
  • Hookworm
  • Necator Americanus
Placebo Comparator: 2
Patients will receive 0.01 % histamine solution.
Other: Histamine
0.01% histamine solution is pipetted onto a plaster dressing.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Primary outcome measure is an increase in the percentage from total CD4+ T cells of CD4+CD25+foxp3+ cells.
Time Frame: End of study
End of study

Secondary Outcome Measures

Outcome Measure
Time Frame
The expression of foxp3 mRNA from peripheral blood mononuclear cells (PBMC).
Time Frame: End of study
End of study
The percentage from total PBMC of NK and NKT cells (CD3-CD56+ and CD3+CD56+ respectively).
Time Frame: End of study
End of study
The percentage from total CD3+ T cells of Tr1 cells (CD3+IL10+ T cells).
Time Frame: End of study
End of study
The percentage from total PBMC of B regulatory cells (CD20+IL-10+).
Time Frame: End of study
End of study

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Nottingham

Investigators

  • Principal Investigator: Cris Constantinescu, MD PhD, University of Nottingham

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

February 1, 2008

Primary Completion (Actual)

May 1, 2008

Study Completion (Actual)

May 1, 2008

Study Registration Dates

First Submitted

February 27, 2008

First Submitted That Met QC Criteria

February 27, 2008

First Posted (Estimate)

March 7, 2008

Study Record Updates

Last Update Posted (Estimate)

June 14, 2012

Last Update Submitted That Met QC Criteria

June 13, 2012

Last Verified

June 1, 2012

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 08025
  • WIRMS-Pilot

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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