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Multiple Sclerosis, Relapsing-RemittingPhase 2WIRMSNCT01470521

Worms for Immune Regulation of Multiple Sclerosis

A Phase 2 study testing Hookworm larvae in people with Multiple Sclerosis, Relapsing-Remitting, run by University of Nottingham at 1 site in United Kingdom.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 65 years
Conditions the study is for
Multiple Sclerosis, Relapsing-Remitting
What is being tested?
Hookworm larvae
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
72 participants
Where
1 siteUnited Kingdom
Study dates
Dec 2011to Jan 2016
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 65 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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)
Show all 17Show fewer
  • 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

Trial locations and contacts

1 site in 1 country.

United Kingdom1 site

  • University of Nottingham

    Nottingham, Nottinghamshire, NG7 2UH

Other trials in United Kingdom

About this study

Official title: Worms for Immune Regulation of Multiple Sclerosis (WIRMS)

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.

Read the 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.

Being tested
Hookworm larvae, Placebo
Keywords
Multiple sclerosis, Hookworm larvae, Necator americanus, Treg cells
Medical subject headings
Multiple Sclerosis, Relapsing-Remitting, Multiple Sclerosis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Hookworm larvaeBiological

    Also called Necator americanus

    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.

  • PlaceboBiological

    Also called Water

    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.

Study groups in NCT01470521
Study groupRoleWhat they receive
Hookworm larvae (Necator americanus)ExperimentalParticipants will receive 25 live hookworm larvae
Receives: Biological: Hookworm larvae
PlaceboPlacebo comparatorParticipant will receive pharmacopoeial grade water
Receives: Biological: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

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

    Measured: Month 9

Secondary outcomes (3)

  1. Percentage of cells positive simultaneously for CD4, CD25, foxp3

    Measured: End of trial

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

    Measured: Month 9

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

    Measured: Month 9

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted11 Nov 2011 (estimated)
  2. Study startDec 2011
  3. Primary completionJan 2016
  4. Study completionJan 2016

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
72 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01470521
Sponsor's protocol ID
08126
Acronym
WIRMS
Status last verified
Jan 2016
First submitted
9 Nov 2011
Last updated
29 Jan 2016
Results posted
No
Data monitoring committee
Yes
Individual data sharing
No

Publications

  • 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.

    PubMed 32539079

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Hookworm larvae in people with Multiple Sclerosis, Relapsing-Remitting, run by University of Nottingham at 1 site in United Kingdom.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 29 Jan 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

The cumulative number of new or enlarging Gd+ lesions at month 9 (time frame: Month 9). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01470521, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Jan 2016; AzTrials last refreshed its copy on 6 Nov 2026.

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