Worms for Immune Regulation of Multiple Sclerosis (WIRMS)

• Sponsor: University of Nottingham
• Collaborator: National Multiple Sclerosis Society
• Information provided by (Responsible Party): University of Nottingham

Tracking Information

• First Submitted Date: November 9, 2011
• First Posted Date: November 11, 2011
• Last Update Posted Date: January 29, 2016
• Study Start Date: December 2011
• Actual Primary Completion Date: January 2016 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: November 15, 2011): The cumulative number of new or enlarging Gd+ lesions at month 9 [ Time Frame: Month 9 ]
• Original Primary Outcome Measures (submitted: November 9, 2011): The cumulative number if new or enlarging Gd+ lesions at month 9 [ Time Frame: Month 9 ]
• Change History: Complete list of historical versions of study NCT01470521 on ClinicalTrials.gov Archive Site

Current Secondary Outcome Measures (submitted: November 9, 2011)

• Percentage of cells positive simultaneously for CD4, CD25, foxp3 [ Time Frame: End of trial ]
• Cumulative number of newly active lesions (new GD+ T1; new and enlarging T2) at month 9 [ Time Frame: Month 9 ]
• Change in expanded disability status scale (EDSS) at month 9 [ Time Frame: Month 9 ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Worms for Immune Regulation of Multiple Sclerosis
• Official Title: Worms for Immune Regulation of Multiple Sclerosis (WIRMS)
• Brief 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.
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Multiple Sclerosis, Relapsing-Remitting

Intervention

• 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.
  Other Name: Necator americanus
• 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.
  Other Name: Water

Study Arms

• Experimental: Hookworm larvae (Necator americanus)
  Participants will receive 25 live hookworm larvae
  Intervention: Biological: Hookworm larvae
• Placebo Comparator: Placebo
  Participant will receive pharmacopoeial grade water
  Intervention: Biological: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: November 9, 2011): 72
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: January 2016
• Actual Primary Completion Date: January 2016 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 65 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United Kingdom

Administrative Information

• NCT Number: NCT01470521
• Other Study ID Numbers: 08126
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: No

• Responsible Party: University of Nottingham
• Study Sponsor: University of Nottingham
• Collaborators: National Multiple Sclerosis Society

Investigators

• Principal Investigator: Cris Constantinescu, MD phD; University of Nottingham

• PRS Account: University of Nottingham
• Verification Date: January 2016