Immune Profiles in Myasthenia Gravis

NCT ID: NCT05095103

Last Updated: 2021-10-27

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Total Enrollment

163 participants

Study Classification

OBSERVATIONAL

Study Start Date

2021-10-31

Study Completion Date

2024-04-30

Brief Summary

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The investigators aim to better describe the immune profile in myasthenia gravis (MG), including lymphocyte subset, cytokine and complement profiles; how they differ between patients of different severity, at times of disease exacerbation, and with different immunosuppressive treatments. The investigators hope to build a clearer picture of how different immune measures vary in MG, contributing to the understanding of the patho\[physiology of the disease, and working towards a biomarker that might help clinicians optimise an individual's treatment.

the investigators aim to take into account the heterogeneity of MG by taking into account age of onset of MG (early vs late onset) and focussing on acetylcholine receptor antibody (AChR) positive, non-thymomatous MG aged 18-80.

Detailed Description

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This study is designed to confirm and refine the knowledge around these changes in the immune profile, including lymphocyte subsets, and complement analysis, between different subgroups of patients with MG of different severity, different levels of immunosuppressive treatment, and at different time points in the disease course, ensuring these are put into the context of the patient's disease subtype (late-onset (LOMG) vs early-onset (EOMG)). This should enable us to understand more about the underlying immune changes in MG, how they relate to disease activity or severity, how this is impacted upon by immunosuppression, and guide us towards a markers for disease severity and effective immunosuppression that could be used in clinical practice, and help guide treatment decisions. One of the challenges in studying patients with MG with the relatively low prevalence of the condition, meaning it can be difficult to recruit large enough numbers of patients; the investigators will work with other tertiary neurology centres throughout England in order to meet recruitment targets.

The research project will consist of three work streams:

1. A one-off observational comparison of the immune profile of patients with different MG severity and in comparison to healthy controls.
2. A prospective observational study examining changes in lymphocyte subset, cytokine and complement profiles associated with clinical exacerbation of myasthenia gravis.
3. A prospective cohort study comparing lymphocyte subset, cytokine and complement profile with disease activity following B cell depletion for refractory myasthenia gravis.

Conditions

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Myasthenia Gravis

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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Stable Immunosuppressed

Acetylcholine repector antibody positvie myasthenia gravis, stable for two years on prednsiolone \<5mg/day and azathioprine or mycophenolate.

No interventions assigned to this group

Stable Non-immunosuppressed

Acetylcholine repector antibody positvie myasthenia gravis, stable for two years on ≤120mg pyridostigmine/day and no immunosuppression.

No interventions assigned to this group

Refractory

Acetylcholine repector antibody positvie myasthenia gravis, meeting the NHS England criteria for Rituximab

No interventions assigned to this group

Healthy Controls

No autoimmune disease or current solid organ or haematological malignancy.

No interventions assigned to this group

Eligibility Criteria

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Inclusion Criteria

* All participants:
* Are able to give valid written consent
* are aged between the ages of 18 and 80

Stable Immunosuppressed

* Have a diagnosis of AChR positive myasthenia gravis (can be ocular, bulbar or generalised)
* MGFA Post-intervention Status MM or better with no clinical relapse for 2 years
* On either azathioprine or MMF along with ≤5mg/day of prednisolone
* No prednisolone dose increase or decrease in past 12 months
* No increase in azathioprine or MMF dose for 2 years (allowing for cessation for up to 1 month)

Stable Non-Immunosuppressed

* have a diagnosis of AChR positive myasthenia gravis (can be ocular, bulbar or generalised)
* MGFA Post-intervention Status MM or better on only low-dose cholinesterase inhibitors (≤\<120 mg pyridostigmine/day) for over two years and ≤5mg/day of prednisolone for over two years.
* No prednisolone dose increase or decrease in past 12 months

Refractory

* have a diagnosis of AChR positive myasthenia gravis (can be ocular, bulbar or generalised)
* have been deemed eligible to be refractory to standard treatment and eligible for rituximab as per the NHS England criteria.

Exclusion Criteria

* Are unable to give valid consent
* Co-existing autoimmune condition for which azathioprine or mycophenolate mofetil are treatments (e.g. inflammatory bowel disease, rheumatoid arthritis, neuromyotonia)
* Currently undergoing treatment for solid organ or haematological malignancy, or previous thymoma
* Clinical frailty scale ≥6
Minimum Eligible Age

18 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Northern Care Alliance NHS Foundation Trust

OTHER

Sponsor Role collaborator

Walton Centre NHS Foundation Trust

OTHER

Sponsor Role collaborator

Oxford University Hospitals NHS Trust

OTHER

Sponsor Role collaborator

University College London Hospitals

OTHER

Sponsor Role collaborator

University Hospital Birmingham NHS Foundation Trust

OTHER

Sponsor Role collaborator

Imperial College Healthcare NHS Trust

OTHER

Sponsor Role collaborator

Newcastle-upon-Tyne Hospitals NHS Trust

OTHER

Sponsor Role collaborator

King's College Hospital NHS Trust

OTHER

Sponsor Role collaborator

Nottingham University Hospitals NHS Trust

OTHER

Sponsor Role collaborator

University Hospital Southampton NHS Foundation Trust

OTHER

Sponsor Role collaborator

Cardiff University

OTHER

Sponsor Role collaborator

University of Manchester

OTHER

Sponsor Role lead

Responsible Party

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Katherine Dodd

Neurology Clinical Research Fellow and PhD Student

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Katherine Dodd, MBChB MRCP

Role: PRINCIPAL_INVESTIGATOR

University of Manchester

Central Contacts

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Katherine Dodd, MBChB MRCP

Role: CONTACT

Phone: 07599 072993

Email: [email protected]

Other Identifiers

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NHS001843

Identifier Type: -

Identifier Source: org_study_id