Immune Profiles in Myasthenia Gravis

NCT05095103 | Unknown

• 1 other identifier: NHS001843
• Study Type: observational
• Target: 163
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Myasthenia Gravis

Outcome Measures

Primary Outcomes (3)

• Primary outcome work stream 1

  Difference in CD19 count between cohorts

  Baseline

• Primary outcome work stream 2

  ● CD27 frequency (% of peripheral blood mononuclear cells) at clinical exacerbation of MG compared to when that patient was clinically stable.

  Relapse within 18 months of recrutiment

• Primary outcome work stream 3

  ● CD27+ frequency (% of peripheral blood mononuclear cells) in MG patients who are symptomatic compared to those who are asymptomatic 12 months following B cell depletion.

  12 months after B cell depletion

Secondary Outcomes (7)

• MG Composite Score

  Baseline, at any clinical relapse within 18 months, 3,6 months after relapse in stable groups or 4 weeks, 6 and 12 months post rituximab in refractory groups,

• MGFA - Post Intervention status

  Baseline, at any clinical relapse within 18 months, 3,6 months after relapse in stable groups or 4 weeks, 6 and 12 months post rituximab in refractory groups

• MG QOL-15r

  Baseline, at any clinical relapse within 18 months, 3,6 months after relapse in stable groups or 4 weeks, 6 and 12 months post rituximab in refractory groups

• Acetylcholine receptor antibody titre

  Baseline, at any clinical relapse within 18 months, 3,6 months after relapse in stable groups or 4 weeks, 6 and 12 months post rituximab in refractory groups

• Lymphocyte Count

  Baseline, at any clinical relapse within 18 months, 3,6 months after relapse in stable groups or 4 weeks, 6 and 12 months post rituximab in refractory groups

Study Arms (4)

Stable Immunosuppressed

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

Stable Non-immunosuppressed

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

Refractory

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

Healthy Controls

No autoimmune disease or current solid organ or haematological malignancy.

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Acetylcholine receptor antibody positive myasthenia gravis

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Manchester: lead
• Northern Care Alliance NHS Foundation Trust: collaborator
• Walton Centre NHS Foundation Trust: collaborator
• Oxford University Hospitals NHS Trust: collaborator
• University College London Hospitals: collaborator
• University Hospital Birmingham NHS Foundation Trust: collaborator
• Imperial College Healthcare NHS Trust: collaborator
• Newcastle-upon-Tyne Hospitals NHS Trust: collaborator
• King's College Hospital NHS Trust: collaborator
• Nottingham University Hospitals NHS Trust: collaborator
• University Hospital Southampton NHS Foundation Trust: collaborator
• Cardiff University: collaborator

MeSH Terms

Conditions

Myasthenia Gravis

Condition Hierarchy (Ancestors)

Paraneoplastic Syndromes, Nervous System; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Paraneoplastic Syndromes; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Neurodegenerative Diseases; Neuromuscular Junction Diseases; Neuromuscular Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• Katherine Dodd, MBChB MRCP

  University of Manchester

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Katherine Dodd, MBChB MRCP

CONTACT

07599 072993; katherine.dodd-3@postgrad.manchester.ac.uk

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Neurology Clinical Research Fellow and PhD Student

Study Record Dates

• First Submitted: September 28, 2021
• First Posted: October 27, 2021
• Study Start: October 1, 2021
• Primary Completion: April 1, 2024
• Study Completion: April 1, 2024
• Last Updated: October 27, 2021

Record last verified: 2021-10

Data Sharing

• IPD Sharing: Will not share