- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01470521
Worms for Immune Regulation of Multiple Sclerosis (WIRMS)
January 28, 2016 updated by: University of Nottingham
Worms for Immune Regulation of Multiple Sclerosis (WIRMS)
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.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
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.
Study Type
Interventional
Enrollment (Actual)
72
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
-
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Nottinghamshire
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Nottingham, Nottinghamshire, United Kingdom, NG7 2UH
- University of Nottingham
-
-
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 65 years (ADULT, OLDER_ADULT)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- Relapsing remitting MS (RRMS) (McDonald criteria) and secondary MS with super imposing relapse on condition that they fulfil the next conditions, MRI scan consistent with MS by Barkhof or Fazekas criteria
- Patients with at least 1 relapse in the last 12 months or 2 in the last 24 months;
- Patients with Expanded disability status scale (EDSS) score in the range of 0 to 5.5 at the screening and week 0 visit
- Patients of both genders, age >18 years and < 65 years
- 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.
- Be able and willing to comply with study visits and procedures per protocol.
- Understand and sign consent form at the screening
Exclusion Criteria:
No populations at risk of severe illness or death will be included in this study
- Life expectancy < 6 months.
- Patient is < 5 years free of malignancy, except treated basal cell skin cancer or cervical carcinoma in situ.
- 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)
- Patients with severe and/or uncontrolled medical condition.
- Pregnancy, lactation or intention to become pregnant during the course of the study (please also see above under inclusion criterion 5)
- Patient has a known diagnosis of human immunodeficiency virus (HIV) infection.
- Anaemia (Hb <10 g/dL for females, <11 g/dL for males)
- Prior or present evidence of parasitic infection; prior treatment with anti-helminthic drugs in the last 6 years.
- Patient with serious medical or psychiatric illness that could potentially interfere with the completion of the study treatment according to this protocol
- 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,
- 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
- Treatment with interferon or glatiramer acetate within 8 weeks prior to baseline or immunosuppressive drugs within 12 weeks prior to baseline
- Treatment with bone marrow transplantation, total lymphoid irradiation, monoclonal antibodies (other than natalizumab, umbilical cord stem cells, AIMSPRO at any time prior to baseline
- Treatment with corticosteroids or ACTH within 4 weeks prior to baseline
- 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: Hookworm larvae (Necator americanus)
Participants will receive 25 live 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.
Other Names:
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PLACEBO_COMPARATOR: Placebo
Participant will receive pharmacopoeial grade water
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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 Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
The cumulative number of new or enlarging Gd+ lesions at month 9
Time Frame: Month 9
|
Month 9
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Percentage of cells positive simultaneously for CD4, CD25, foxp3
Time Frame: End of trial
|
End of trial
|
Cumulative number of newly active lesions (new GD+ T1; new and enlarging T2) at month 9
Time Frame: Month 9
|
Month 9
|
Change in expanded disability status scale (EDSS) at month 9
Time Frame: Month 9
|
Month 9
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Collaborators
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.
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
December 1, 2011
Primary Completion (ACTUAL)
January 1, 2016
Study Completion (ACTUAL)
January 1, 2016
Study Registration Dates
First Submitted
November 9, 2011
First Submitted That Met QC Criteria
November 9, 2011
First Posted (ESTIMATE)
November 11, 2011
Study Record Updates
Last Update Posted (ESTIMATE)
January 29, 2016
Last Update Submitted That Met QC Criteria
January 28, 2016
Last Verified
January 1, 2016
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 08126
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
NO
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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