Ignite Creation Date:
2025-12-24 @ 7:17 PM
Ignite Modification Date:
2025-12-25 @ 4:54 PM
Study NCT ID:
NCT05095103
Status:
UNKNOWN
Last Update Posted:
2021-10-27
First Post:
2021-09-28
Is NOT Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
Immune Profiles in Myasthenia Gravis
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D009157', 'term': 'Myasthenia Gravis'}], 'ancestors': [{'id': 'D020361', 'term': 'Paraneoplastic Syndromes, Nervous System'}, {'id': 'D009423', 'term': 'Nervous System Neoplasms'}, {'id': 'D009371', 'term': 'Neoplasms by Site'}, {'id': 'D009369', 'term': 'Neoplasms'}, {'id': 'D010257', 'term': 'Paraneoplastic Syndromes'}, {'id': 'D020274', 'term': 'Autoimmune Diseases of the Nervous System'}, {'id': 'D009422', 'term': 'Nervous System Diseases'}, {'id': 'D019636', 'term': 'Neurodegenerative Diseases'}, {'id': 'D020511', 'term': 'Neuromuscular Junction Diseases'}, {'id': 'D009468', 'term': 'Neuromuscular Diseases'}, {'id': 'D001327', 'term': 'Autoimmune Diseases'}, {'id': 'D007154', 'term': 'Immune System Diseases'}]}}, 'protocolSection': {'designModule': {'studyType': 'OBSERVATIONAL', 'designInfo': {'timePerspective': 'PROSPECTIVE', 'observationalModel': 'COHORT'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 163}, 'patientRegistry': False}, 'statusModule': {'overallStatus': 'UNKNOWN', 'lastKnownStatus': 'NOT_YET_RECRUITING', 'startDateStruct': {'date': '2021-10', 'type': 'ESTIMATED'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2021-10', 'completionDateStruct': {'date': '2024-04', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2021-10-13', 'studyFirstSubmitDate': '2021-09-28', 'studyFirstSubmitQcDate': '2021-10-13', 'lastUpdatePostDateStruct': {'date': '2021-10-27', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2021-10-27', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2024-04', 'type': 'ESTIMATED'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Primary outcome work stream 1', 'timeFrame': 'Baseline', 'description': 'Difference in CD19 count between cohorts'}, {'measure': 'Primary outcome work stream 2', 'timeFrame': 'Relapse within 18 months of recrutiment', 'description': '● CD27 frequency (% of peripheral blood mononuclear cells) at clinical exacerbation of MG compared to when that patient was clinically stable.'}, {'measure': 'Primary outcome work stream 3', 'timeFrame': '12 months after B cell depletion', 'description': '● 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.'}], 'secondaryOutcomes': [{'measure': 'MG Composite Score', 'timeFrame': '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,'}, {'measure': 'MGFA - Post Intervention status', 'timeFrame': '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'}, {'measure': 'MG QOL-15r', 'timeFrame': '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'}, {'measure': 'Acetylcholine receptor antibody titre', 'timeFrame': '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'}, {'measure': 'Lymphocyte Count', 'timeFrame': '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'}, {'measure': 'Number of relapses requiring hospital admission or rescue therapy', 'timeFrame': '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'}, {'measure': 'Average daily dose of prednisolone over the three months prior to review', 'timeFrame': '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'}]}, 'oversightModule': {'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'conditions': ['Myasthenia Gravis']}, 'descriptionModule': {'briefSummary': "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.\n\nthe 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.", 'detailedDescription': "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.\n\nThe research project will consist of three work streams:\n\n1. A one-off observational comparison of the immune profile of patients with different MG severity and in comparison to healthy controls.\n2. A prospective observational study examining changes in lymphocyte subset, cytokine and complement profiles associated with clinical exacerbation of myasthenia gravis.\n3. A prospective cohort study comparing lymphocyte subset, cytokine and complement profile with disease activity following B cell depletion for refractory myasthenia gravis."}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'maximumAge': '80 Years', 'minimumAge': '18 Years', 'samplingMethod': 'NON_PROBABILITY_SAMPLE', 'studyPopulation': 'Acetylcholine receptor antibody positive myasthenia gravis', 'healthyVolunteers': True, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* All participants:\n* Are able to give valid written consent\n* are aged between the ages of 18 and 80\n\nStable Immunosuppressed\n\n* Have a diagnosis of AChR positive myasthenia gravis (can be ocular, bulbar or generalised)\n* MGFA Post-intervention Status MM or better with no clinical relapse for 2 years\n* On either azathioprine or MMF along with ≤5mg/day of prednisolone\n* No prednisolone dose increase or decrease in past 12 months\n* No increase in azathioprine or MMF dose for 2 years (allowing for cessation for up to 1 month)\n\nStable Non-Immunosuppressed\n\n* have a diagnosis of AChR positive myasthenia gravis (can be ocular, bulbar or generalised)\n* 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.\n* No prednisolone dose increase or decrease in past 12 months\n\nRefractory\n\n* have a diagnosis of AChR positive myasthenia gravis (can be ocular, bulbar or generalised)\n* have been deemed eligible to be refractory to standard treatment and eligible for rituximab as per the NHS England criteria.\n\nExclusion Criteria for all participants:\n\n* Are unable to give valid consent\n* Co-existing autoimmune condition for which azathioprine or mycophenolate mofetil are treatments (e.g. inflammatory bowel disease, rheumatoid arthritis, neuromyotonia)\n* Currently undergoing treatment for solid organ or haematological malignancy, or previous thymoma\n* Clinical frailty scale ≥6'}, 'identificationModule': {'nctId': 'NCT05095103', 'briefTitle': 'Immune Profiles in Myasthenia Gravis', 'organization': {'class': 'OTHER', 'fullName': 'University of Manchester'}, 'officialTitle': 'Comparison of Lymphocyte Subset, Cytokine and Complement Profiles in Myasthenia Gravis of Different Severity, Disease Time-points, and Treatment History', 'orgStudyIdInfo': {'id': 'NHS001843'}}, 'armsInterventionsModule': {'armGroups': [{'label': 'Stable Immunosuppressed', 'description': 'Acetylcholine repector antibody positvie myasthenia gravis, stable for two years on prednsiolone \\<5mg/day and azathioprine or mycophenolate.'}, {'label': 'Stable Non-immunosuppressed', 'description': 'Acetylcholine repector antibody positvie myasthenia gravis, stable for two years on ≤120mg pyridostigmine/day and no immunosuppression.'}, {'label': 'Refractory', 'description': 'Acetylcholine repector antibody positvie myasthenia gravis, meeting the NHS England criteria for Rituximab'}, {'label': 'Healthy Controls', 'description': 'No autoimmune disease or current solid organ or haematological malignancy.'}]}, 'contactsLocationsModule': {'centralContacts': [{'name': 'Katherine Dodd, MBChB MRCP', 'role': 'CONTACT', 'email': 'katherine.dodd-3@postgrad.manchester.ac.uk', 'phone': '07599 072993'}], 'overallOfficials': [{'name': 'Katherine Dodd, MBChB MRCP', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'University of Manchester'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'University of Manchester', 'class': 'OTHER'}, 'collaborators': [{'name': 'Northern Care Alliance NHS Foundation Trust', 'class': 'OTHER'}, {'name': 'Walton Centre NHS Foundation Trust', 'class': 'OTHER'}, {'name': 'Oxford University Hospitals NHS Trust', 'class': 'OTHER'}, {'name': 'University College London Hospitals', 'class': 'OTHER'}, {'name': 'University Hospital Birmingham NHS Foundation Trust', 'class': 'OTHER'}, {'name': 'Imperial College Healthcare NHS Trust', 'class': 'OTHER'}, {'name': 'Newcastle-upon-Tyne Hospitals NHS Trust', 'class': 'OTHER'}, {'name': "King's College Hospital NHS Trust", 'class': 'OTHER'}, {'name': 'Nottingham University Hospitals NHS Trust', 'class': 'OTHER'}, {'name': 'University Hospital Southampton NHS Foundation Trust', 'class': 'OTHER'}, {'name': 'Cardiff University', 'class': 'OTHER'}], 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'Neurology Clinical Research Fellow and PhD Student', 'investigatorFullName': 'Katherine Dodd', 'investigatorAffiliation': 'University of Manchester'}}}}