Immune Profiles in Myasthenia Gravis

Myasthenia Gravis Clinical Trial

Official title:

Comparison of Lymphocyte Subset, Cytokine and Complement Profiles in Myasthenia Gravis of Different Severity, Disease Time-points, and Treatment History

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05095103
• Other study ID #: NHS001843
• Status: Not yet recruiting
• Start date: October 2021
• Est. completion date: April 2024

Study information

• Verified date: October 2021
• Source: University of Manchester
• Contact: Katherine Dodd, MBChB MRCP
• Phone: 07599 072993
• Email: katherine.dodd-3[@]postgrad.manchester.ac.uk
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

Description:

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 163
• Est. completion date: April 2024
• Est. primary completion date: April 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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 for all participants:

• 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

Related Conditions & MeSH terms

• Muscle Weakness
• Myasthenia Gravis

Locations

Country	Name	City	State
n/a

Sponsors (12)

Lead Sponsor

Collaborator

University of Manchester

Cardiff University, Imperial College Healthcare NHS Trust, King's College Hospital NHS Trust, Newcastle-upon-Tyne Hospitals NHS Trust, Nottingham University Hospitals NHS Trust, Oxford University Hospitals NHS Trust, Salford Royal NHS Foundation Trust, University College London Hospitals, University Hospital Birmingham NHS Foundation Trust, University Hospital Southampton NHS Foundation Trust, Walton Centre NHS Foundation Trust

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Primary outcome work stream 1	Difference in CD19 count between cohorts	Baseline
Primary	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	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	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,
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Number of relapses requiring hospital admission or rescue therapy		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
Secondary	Average daily dose of prednisolone over the three months prior to review		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