Worms for Immune Regulation of Multiple Sclerosis

NCT01470521 | Completed Phase 2 DMC

• 1 other identifier: 08126
• Study Type: interventional
• Target: 72
• Locations: 1 country
• Sites: 1

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.

Conditions

Multiple Sclerosis, Relapsing-Remitting

Keywords

Multiple sclerosis; Hookworm larvae; Necator americanus; Treg cells

Outcome Measures

Primary Outcomes (1)

• The cumulative number of new or enlarging Gd+ lesions at month 9

  Month 9

Secondary Outcomes (3)

• Percentage of cells positive simultaneously for CD4, CD25, foxp3

  End of trial

• Cumulative number of newly active lesions (new GD+ T1; new and enlarging T2) at month 9

  Month 9

• Change in expanded disability status scale (EDSS) at month 9

  Month 9

Study Arms (2)

Hookworm larvae (Necator americanus)

EXPERIMENTAL

Participants will receive 25 live hookworm larvae

Biological: Hookworm larvae

Placebo

PLACEBO COMPARATOR

Participant will receive pharmacopoeial grade water

Biological: Placebo

Interventions

Hookworm larvae BIOLOGICAL

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.

Also known as: Necator americanus

Hookworm larvae (Necator americanus)

Placebo BIOLOGICAL

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.

Also known as: Water

Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

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 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

Sponsors & Collaborators

• University of Nottingham: lead
• National Multiple Sclerosis Society: collaborator

Study Sites (1)

University of Nottingham

Nottingham, Nottinghamshire, NG7 2UH, United Kingdom

Location

Related Publications (1)

• Tanasescu R, Tench CR, Constantinescu CS, Telford G, Singh S, Frakich N, Onion D, Auer DP, Gran B, Evangelou N, Falah Y, Ranshaw C, Cantacessi C, Jenkins TP, Pritchard DI. Hookworm Treatment for Relapsing Multiple Sclerosis: A Randomized Double-Blinded Placebo-Controlled Trial. JAMA Neurol. 2020 Sep 1;77(9):1089-1098. doi: 10.1001/jamaneurol.2020.1118.

  PMID: 32539079 DERIVED

MeSH Terms

Conditions

Multiple Sclerosis, Relapsing-Remitting; Multiple Sclerosis

Interventions

ASP-1 protein, Necator americanus; Water

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Hydroxides; Alkalies; Inorganic Chemicals; Anions; Ions; Electrolytes; Oxides; Oxygen Compounds

Study Officials

• Cris Constantinescu, MD phD

  University of Nottingham

  PRINCIPAL INVESTIGATOR

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: November 9, 2011
• First Posted: November 11, 2011
• Study Start: December 1, 2011
• Primary Completion: January 1, 2016
• Study Completion: January 1, 2016
• Last Updated: January 29, 2016

Record last verified: 2016-01

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)