Worms for Immune Regulation of Multiple Sclerosis (WIRMS)

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2012 by University of Nottingham
Sponsor:
Collaborator:
National Multiple Sclerosis Society
Information provided by (Responsible Party):
University of Nottingham
ClinicalTrials.gov Identifier:
NCT01470521
First received: November 9, 2011
Last updated: October 4, 2012
Last verified: October 2012
  Purpose

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.


Condition Intervention Phase
Multiple Sclerosis, Relapsing-Remitting
Biological: Hookworm larvae
Biological: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Worms for Immune Regulation of Multiple Sclerosis (WIRMS)

Resource links provided by NLM:


Further study details as provided by University of Nottingham:

Primary Outcome Measures:
  • The cumulative number of new or enlarging Gd+ lesions at month 9 [ Time Frame: Month 9 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Percentage of cells positive simultaneously for CD4, CD25, foxp3 [ Time Frame: End of trial ] [ Designated as safety issue: No ]
  • Cumulative number of newly active lesions (new GD+ T1; new and enlarging T2) at month 9 [ Time Frame: Month 9 ] [ Designated as safety issue: No ]
  • Change in expanded disability status scale (EDSS) at month 9 [ Time Frame: Month 9 ] [ Designated as safety issue: No ]

Estimated Enrollment: 72
Study Start Date: December 2011
Estimated Study Completion Date: November 2014
Estimated Primary Completion Date: November 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Hookworm larvae (Necator americanus)
Participants will receive 25 live hookworm larvae
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
Placebo Comparator: Placebo
Participant will receive pharmacopoeial grade water
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

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.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01470521

Contacts
Contact: Cris Constantinescu, MD PhD 01158754597 cris.constantinescu@nottingham.ac.uk
Contact: Bruno Gran, MD PhD 01158231442 bruno.gran@nottingham.ac.uk

Locations
United Kingdom
University of Nottingham Recruiting
Nottingham, Nottinghamshire, United Kingdom, NG7 2UH
Contact: Cris Constantinescu, MD PhD    0115 8754597    cris.constantinescu@nottingham.ac.uk   
Principal Investigator: Cris Constantinescu, MD PhD         
Sub-Investigator: David Pritchard, PhD         
Sponsors and Collaborators
University of Nottingham
National Multiple Sclerosis Society
Investigators
Principal Investigator: Cris Constantinescu, MD phD University of Nottingham
  More Information

No publications provided

Responsible Party: University of Nottingham
ClinicalTrials.gov Identifier: NCT01470521     History of Changes
Other Study ID Numbers: 08126
Study First Received: November 9, 2011
Last Updated: October 4, 2012
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by University of Nottingham:
Multiple sclerosis
Hookworm larvae
Necator americanus
Treg cells

Additional relevant MeSH terms:
Sclerosis
Multiple Sclerosis
Multiple Sclerosis, Relapsing-Remitting
Pathologic Processes
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases

ClinicalTrials.gov processed this record on October 19, 2014