Myasthenia GravisNCT05095103
Immune Profiles in Myasthenia Gravis
An observational study of Myasthenia Gravis, run by University of Manchester.
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. Read more about this study
- Who is it for?
- Ages 18 to 80 yearsHealthy volunteers can take part
- Conditions the study is for
- Myasthenia Gravis
- How many people
- 163 participants
- Where
- No sites listed yet
- Study dates
- Oct 2021to Apr 2024
- Phase
- Observational
- 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 80 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: Acetylcholine receptor antibody positive myasthenia gravis
Who may be able to join
- 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
Show all 16Show fewer
- 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.
Who cannot join
- 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
Trial locations and contacts
No sites are listed yet.
About this study
Official title: Comparison of Lymphocyte Subset, Cytokine and Complement Profiles in Myasthenia Gravis of Different Severity, Disease Time-points, and Treatment History
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.
Read the detailed 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:
- A one-off observational comparison of the immune profile of patients with different MG severity and in comparison to healthy controls.
- A prospective observational study examining changes in lymphocyte subset, cytokine and complement profiles associated with clinical exacerbation of myasthenia gravis.
- A prospective cohort study comparing lymphocyte subset, cytokine and complement profile with disease activity following B cell depletion for refractory myasthenia gravis.
- Conditions
- Myasthenia Gravis
- Medical subject headings
- Myasthenia Gravis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| 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. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Primary outcome work stream 1
Difference in CD19 count between cohorts
Measured: 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.
Measured: 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.
Measured: 12 months after B cell depletion
Secondary outcomes (7)
MG Composite Score
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Number of relapses requiring hospital admission or rescue therapy
Measured: 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
Average daily dose of prednisolone over the three months prior to review
Measured: 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
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Oct 2021
- Study startOct 2021 (estimated)
- Primary completionApr 2024 (estimated)
- Study completionApr 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Myasthenia GravisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 163 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Manchester
- Sponsor type
- University, hospital or other
- Collaborators
- Northern Care Alliance NHS Foundation Trust, Walton Centre NHS Foundation Trust, Oxford University Hospitals NHS Trust, University College London Hospitals, University Hospital Birmingham NHS Foundation Trust, Imperial College Healthcare NHS Trust, Newcastle-upon-Tyne Hospitals NHS Trust, King's College Hospital NHS Trust, Nottingham University Hospitals NHS Trust, University Hospital Southampton NHS Foundation Trust, Cardiff University
- Responsible party
- Principal investigator, Katherine Dodd, University of Manchester
- Investigators
- Katherine Dodd, MBChB MRCP, Principal investigator, University of Manchester
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05095103
- Sponsor's protocol ID
- NHS001843
- Status last verified
- Oct 2021
- First submitted
- 28 Sep 2021
- Last updated
- 27 Oct 2021
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Oct 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Comparison of Lymphocyte Subset, Cytokine and Complement Profiles in Myasthenia Gravis of Different Severity, Disease Time-points, and Treatment History
- ClinicalTrials.gov ID
- NCT05095103
- Acronym / sponsor ID
- NHS001843
- Conditions
- Myasthenia Gravis
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 163 participants (estimated)
- Lead sponsor
- University of ManchesterUniversity, hospital or other
- Collaborators
- Northern Care Alliance NHS Foundation Trust, Walton Centre NHS Foundation Trust, Oxford University Hospitals NHS Trust, University College London Hospitals, University Hospital Birmingham NHS Foundation Trust, Imperial College Healthcare NHS Trust, Newcastle-upon-Tyne Hospitals NHS Trust, King's College Hospital NHS Trust, Nottingham University Hospitals NHS Trust, University Hospital Southampton NHS Foundation Trust, Cardiff University
- Study start
- Oct 2021 (estimated)
- Primary completion
- Apr 2024 (estimated)
- Study completion
- Apr 2024 (estimated)
- First posted
- 27 Oct 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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:
- A one-off observational comparison of the immune profile of patients with different MG severity and in comparison to healthy controls.
- A prospective observational study examining changes in lymphocyte subset, cytokine and complement profiles associated with clinical exacerbation of myasthenia gravis.
- A prospective cohort study comparing lymphocyte subset, cytokine and complement profile with disease activity following B cell depletion for refractory myasthenia gravis.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| 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. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Acetylcholine receptor antibody positive myasthenia gravis
Key inclusion criteria (16 listed)
- 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)
Key exclusion criteria (4 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Primary outcome work stream 1
Time frame: Baseline
Difference in CD19 count between cohorts
Primary outcome work stream 2
Time frame: Relapse within 18 months of recrutiment
● CD27 frequency (% of peripheral blood mononuclear cells) at clinical exacerbation of MG compared to when that patient was clinically stable.
Primary outcome work stream 3
Time frame: 12 months after B cell depletion
● 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.
7 secondary outcomes
MG Composite Score
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Number of relapses requiring hospital admission or rescue therapy
Time frame: 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
Average daily dose of prednisolone over the three months prior to review
Time frame: 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
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Oct 2021.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Katherine Dodd, MBChB MRCP principal investigator
University of Manchester
Questions about this trial
What is this clinical trial studying?
An observational study of Myasthenia Gravis, run by University of Manchester.
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 16 inclusion and 4 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: status not confirmed, as of the sponsor's last update on 27 Oct 2021. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Katherine Dodd, MBChB MRCP (07599 072993, katherine.dodd-3@postgrad.manchester.ac.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Primary outcome work stream 1 (time frame: Baseline). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 27 Oct 2021; AzTrials last refreshed its copy on 31 Oct 2026.