Immunoregulation by Controlled Parasite Exposure in Multiple Sclerosis.
NCT ID: NCT00630383
Last Updated: 2012-06-14
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
WITHDRAWN
PHASE2
INTERVENTIONAL
2008-02-29
2008-05-31
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
Related Clinical Trials
Explore similar clinical trials based on study characteristics and research focus.
Worms for Immune Regulation of Multiple Sclerosis
NCT01470521
Safety of RG2077 in Patients With Multiple Sclerosis
NCT00076934
Natalizumab Subcutaneous Immunogenicity and Safety Study
NCT02142192
Exploratory Study of the Safety, Tolerability and Efficacy of Multiple Regimens of Natalizumab in Adult Participants With Relapsing Multiple Sclerosis (MS)
NCT01405820
Study to Investigate the Immune Response and Safety of Prophylactic Vaccines in Patients Treated for Multiple Sclerosis
NCT02275741
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
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.
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
RANDOMIZED
PARALLEL
TREATMENT
QUADRUPLE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
1
Patients will receive 25 live hookworm larvae.
Live Hookworm Larvae
25 live hookworm will be applied to the arm and will infect transdermally. They will be eradicated after 48 weeks.
2
Patients will receive 0.01 % histamine solution.
Histamine
0.01% histamine solution is pipetted onto a plaster dressing.
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
Live Hookworm Larvae
25 live hookworm will be applied to the arm and will infect transdermally. They will be eradicated after 48 weeks.
Histamine
0.01% histamine solution is pipetted onto a plaster dressing.
Other Intervention Names
Discover alternative or legacy names that may be used to describe the listed interventions across different sources.
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion 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
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
18 Years
60 Years
ALL
No
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
University of Nottingham
OTHER
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
Cris Constantinescu, MD PhD
Role: PRINCIPAL_INVESTIGATOR
University of Nottingham
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
Nottingham University Hospital NHS Trust
Nottingham, Nottinghamshire, United Kingdom
Countries
Review the countries where the study has at least one active or historical site.
References
Explore related publications, articles, or registry entries linked to this study.
Bach JF. The effect of infections on susceptibility to autoimmune and allergic diseases. N Engl J Med. 2002 Sep 19;347(12):911-20. doi: 10.1056/NEJMra020100. No abstract available.
Edwards LJ, Constantinescu CS. A prospective study of conditions associated with multiple sclerosis in a cohort of 658 consecutive outpatients attending a multiple sclerosis clinic. Mult Scler. 2004 Oct;10(5):575-81. doi: 10.1191/1352458504ms1087oa.
Steinman L. A brief history of T(H)17, the first major revision in the T(H)1/T(H)2 hypothesis of T cell-mediated tissue damage. Nat Med. 2007 Feb;13(2):139-45. doi: 10.1038/nm1551.
Viglietta V, Baecher-Allan C, Weiner HL, Hafler DA. Loss of functional suppression by CD4+CD25+ regulatory T cells in patients with multiple sclerosis. J Exp Med. 2004 Apr 5;199(7):971-9. doi: 10.1084/jem.20031579.
Fleming JO, Cook TD. Multiple sclerosis and the hygiene hypothesis. Neurology. 2006 Dec 12;67(11):2085-6. doi: 10.1212/01.wnl.0000247663.40297.2d. No abstract available.
Correale J, Farez M. Association between parasite infection and immune responses in multiple sclerosis. Ann Neurol. 2007 Feb;61(2):97-108. doi: 10.1002/ana.21067.
Sewell D, Qing Z, Reinke E, Elliot D, Weinstock J, Sandor M, Fabry Z. Immunomodulation of experimental autoimmune encephalomyelitis by helminth ova immunization. Int Immunol. 2003 Jan;15(1):59-69. doi: 10.1093/intimm/dxg012.
Mortimer K, Brown A, Feary J, Jagger C, Lewis S, Antoniak M, Pritchard D, Britton J. Dose-ranging study for trials of therapeutic infection with Necator americanus in humans. Am J Trop Med Hyg. 2006 Nov;75(5):914-20.
Compston A, Coles A. Multiple sclerosis. Lancet. 2002 Apr 6;359(9313):1221-31. doi: 10.1016/S0140-6736(02)08220-X.
Hotez PJ, Pritchard DI. Hookworm infection. Sci Am. 1995 Jun;272(6):68-74. doi: 10.1038/scientificamerican0695-68.
Falcone FH, Pritchard DI. Parasite role reversal: worms on trial. Trends Parasitol. 2005 Apr;21(4):157-60. doi: 10.1016/j.pt.2005.02.002.
Raine T, Zaccone P, Dunne DW, Cooke A. Can helminth antigens be exploited therapeutically to downregulate pathological Th1 responses? Curr Opin Investig Drugs. 2004 Nov;5(11):1184-91.
Quinnell RJ, Bethony J, Pritchard DI. The immunoepidemiology of human hookworm infection. Parasite Immunol. 2004 Nov-Dec;26(11-12):443-54. doi: 10.1111/j.0141-9838.2004.00727.x.
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
WIRMS-Pilot
Identifier Type: -
Identifier Source: secondary_id
08025
Identifier Type: -
Identifier Source: org_study_id
More Related Trials
Additional clinical trials that may be relevant based on similarity analysis.