NCT00630383

Brief Summary

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.

Trial Health

30
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Timeline
Completed

Started Feb 2008

Shorter than P25 for phase_2 multiple-sclerosis

Geographic Reach
1 country

1 active site

Status
withdrawn

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

February 1, 2008

Completed
26 days until next milestone

First Submitted

Initial submission to the registry

February 27, 2008

Completed
9 days until next milestone

First Posted

Study publicly available on registry

March 7, 2008

Completed
2 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 1, 2008

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

May 1, 2008

Completed
Last Updated

June 14, 2012

Status Verified

June 1, 2012

Enrollment Period

3 months

First QC Date

February 27, 2008

Last Update Submit

June 13, 2012

Conditions

Multiple Sclerosis

Keywords

ParasiteNecatorimmune regulationregulatory T cellsfoxp3cytokinesmultiple sclerosishygiene hypothesis

Outcome Measures

Primary Outcomes (1)

  • Primary outcome measure is an increase in the percentage from total CD4+ T cells of CD4+CD25+foxp3+ cells.

    End of study

Secondary Outcomes (4)

  • The expression of foxp3 mRNA from peripheral blood mononuclear cells (PBMC).

    End of study

  • The percentage from total PBMC of NK and NKT cells (CD3-CD56+ and CD3+CD56+ respectively).

    End of study

  • The percentage from total CD3+ T cells of Tr1 cells (CD3+IL10+ T cells).

    End of study

  • The percentage from total PBMC of B regulatory cells (CD20+IL-10+).

    End of study

Study Arms (2)

1

EXPERIMENTAL

Patients will receive 25 live hookworm larvae.

Biological: Live Hookworm Larvae

2

PLACEBO COMPARATOR

Patients will receive 0.01 % histamine solution.

Other: Histamine

Interventions

Live Hookworm LarvaeBIOLOGICAL

25 live hookworm will be applied to the arm and will infect transdermally. They will be eradicated after 48 weeks.

Also known as: Hookworm, Necator Americanus
1
HistamineOTHER

0.01% histamine solution is pipetted onto a plaster dressing.

2

Eligibility Criteria

Age18 Years - 60 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64)

You may qualify if:

  • 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
  • Patients with at least 1 relapse in the last 12 months
  • Patients with EDSS score in the range of 0 to 5.5 at the baseline visit
  • Patients of both genders, age \>18 years and \< 60 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, sign, and date the written voluntary informed consent form at the screening visit prior to any protocol-specific procedures performed.

You may not qualify if:

  • 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.
  • 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
  • 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 or immunosuppressive drugs within 26 weeks prior to baseline
  • Treatment with bone marrow transplantation, total lymphoid irradiation, monoclonal antibodies, umbilical cord stem cells, AIMSPRO at any time prior to baseline
  • Treatment with corticosteroids or ACTH within 4 weeks prior to baseline
  • +1 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Nottingham University Hospital NHS Trust

Nottingham, Nottinghamshire, NG7 2UH, United Kingdom

Location

Related Publications (13)

  • 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.

    PMID: 12239261BACKGROUND

  • 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.

    PMID: 15471376BACKGROUND

  • 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.

    PMID: 17290272BACKGROUND

  • 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.

    PMID: 15067033BACKGROUND

  • 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.

    PMID: 17159130BACKGROUND

  • 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.

    PMID: 17230481BACKGROUND

  • 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.

    PMID: 12502726BACKGROUND

  • 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.

    PMID: 17123987BACKGROUND

  • Compston A, Coles A. Multiple sclerosis. Lancet. 2002 Apr 6;359(9313):1221-31. doi: 10.1016/S0140-6736(02)08220-X.

    PMID: 11955556BACKGROUND

  • Hotez PJ, Pritchard DI. Hookworm infection. Sci Am. 1995 Jun;272(6):68-74. doi: 10.1038/scientificamerican0695-68.

    PMID: 7761817BACKGROUND

  • 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.

    PMID: 15780835BACKGROUND

  • 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.

    PMID: 15573869BACKGROUND

  • 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.

    PMID: 15771680BACKGROUND

MeSH Terms

Conditions

Multiple Sclerosis

Interventions

ASP-1 protein, Necator americanusHistamine

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNSAutoimmune Diseases of the Nervous SystemNervous System DiseasesDemyelinating DiseasesAutoimmune DiseasesImmune System Diseases

Intervention Hierarchy (Ancestors)

Biogenic MonoaminesBiogenic AminesAminesOrganic ChemicalsEthylaminesImidazolesAzolesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsAutacoidsInflammation MediatorsBiological Factors

Study Officials

  • Cris Constantinescu, MD PhD

    University of Nottingham

    PRINCIPAL INVESTIGATOR
0

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

February 27, 2008

First Posted

March 7, 2008

Study Start

February 1, 2008

Primary Completion

May 1, 2008

Study Completion

May 1, 2008

Last Updated

June 14, 2012

Record last verified: 2012-06

Locations

GB(1)