Ignite Creation Date:
2025-12-25 @ 2:30 AM
Ignite Modification Date:
2025-12-30 @ 10:17 AM
Study NCT ID:
NCT06827834
Status:
RECRUITING
Last Update Posted:
2025-02-14
First Post:
2025-01-27
Is Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Spinal Cord Monitoring in Multiple Sclerosis
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D009103', 'term': 'Multiple Sclerosis'}], 'ancestors': [{'id': 'D020278', 'term': 'Demyelinating Autoimmune Diseases, CNS'}, {'id': 'D020274', 'term': 'Autoimmune Diseases of the Nervous System'}, {'id': 'D009422', 'term': 'Nervous System Diseases'}, {'id': 'D003711', 'term': 'Demyelinating 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': 155}, 'patientRegistry': False}, 'statusModule': {'overallStatus': 'RECRUITING', 'startDateStruct': {'date': '2024-08-06', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2025-01', 'completionDateStruct': {'date': '2028-06-01', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2025-02-10', 'studyFirstSubmitDate': '2025-01-27', 'studyFirstSubmitQcDate': '2025-02-10', 'lastUpdatePostDateStruct': {'date': '2025-02-14', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2025-02-14', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2028-06-01', 'type': 'ESTIMATED'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Spinal cord lesion count', 'timeFrame': '27 months'}], 'secondaryOutcomes': [{'measure': 'Brain MRI acitivity', 'timeFrame': '27 months', 'description': 'Number of new (new T2, T1 gadolinium-enhancing) and expanding lesions'}, {'measure': 'Expanded disability status scale (EDSS)', 'timeFrame': '27 months', 'description': 'Measured at 3, 15 and 27 months'}, {'measure': 'Timed 25 foot walk test', 'timeFrame': '27 months', 'description': 'Measured at 3, 15 and 27 months'}, {'measure': 'Nine hole peg test', 'timeFrame': '27 months', 'description': 'Measured at 3, 15 and 27 months'}, {'measure': 'No evidence of disease activity', 'timeFrame': '27 months', 'description': 'Composite outcome: no relapses, no progression independent of relapse activity, no new lesions on brain or spinal cord MRI'}, {'measure': 'Biomarkers neuronal damage', 'timeFrame': '27 months', 'description': 'Neurofilament light chain (Nfl) and glial fibrillary acidic protein (GFAP)'}, {'measure': 'Lower urinary tract symptoms', 'timeFrame': '27 months', 'description': '* For females: International Consultation on Incontinence Questionnaire Female Lower Urinary Tract Symptoms Module (ICIQ-FLUTS)\n* For males: International Consultation on Incontinence Questionnaire Male Lower Urinary Tract Symptoms Module (ICIQ-MLUTS)'}]}, 'oversightModule': {'isUsExport': False, 'oversightHasDmc': False, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['spinal cord', 'mri', 'biomarkers', 'multiple sclerosis'], 'conditions': ['Multiple Sclerosis']}, 'referencesModule': {'references': [{'pmid': '34820734', 'type': 'BACKGROUND', 'citation': 'Di Sabatino E, Gaetani L, Sperandei S, Fiacca A, Guercini G, Parnetti L, Di Filippo M. The no evidence of disease activity (NEDA) concept in MS: impact of spinal cord MRI. J Neurol. 2022 Jun;269(6):3129-3135. doi: 10.1007/s00415-021-10901-2. Epub 2021 Nov 24.'}, {'pmid': '37683557', 'type': 'BACKGROUND', 'citation': 'Kreiter D, Spee R, Merry A, Hupperts R, Gerlach O. Effect of disease-modifying treatment on spinal cord lesion formation in multiple sclerosis: A retrospective observational study. Mult Scler Relat Disord. 2023 Nov;79:104994. doi: 10.1016/j.msard.2023.104994. Epub 2023 Sep 4.'}, {'pmid': '27481210', 'type': 'BACKGROUND', 'citation': 'Brownlee WJ, Altmann DR, Alves Da Mota P, Swanton JK, Miszkiel KA, Wheeler-Kingshott CG, Ciccarelli O, Miller DH. Association of asymptomatic spinal cord lesions and atrophy with disability 5 years after a clinically isolated syndrome. Mult Scler. 2017 Apr;23(5):665-674. doi: 10.1177/1352458516663034. Epub 2016 Aug 6.'}, {'pmid': '31494713', 'type': 'BACKGROUND', 'citation': 'Granella F, Tsantes E, Graziuso S, Bazzurri V, Crisi G, Curti E. Spinal cord lesions are frequently asymptomatic in relapsing-remitting multiple sclerosis: a retrospective MRI survey. J Neurol. 2019 Dec;266(12):3031-3037. doi: 10.1007/s00415-019-09526-3. Epub 2019 Sep 7.'}, {'pmid': '26459149', 'type': 'BACKGROUND', 'citation': 'Zecca C, Disanto G, Sormani MP, Riccitelli GC, Cianfoni A, Del Grande F, Pravata E, Gobbi C. Relevance of asymptomatic spinal MRI lesions in patients with multiple sclerosis. Mult Scler. 2016 May;22(6):782-91. doi: 10.1177/1352458515599246. Epub 2015 Oct 12.'}]}, 'descriptionModule': {'briefSummary': 'Multiple sclerosis (MS) is the most common demyelinating disease of the central nervous system and the most common cause of non-traumatic neurological disability in young adults. Magnetic resonance imaging (MRI) is the most important paraclinical investigation used in the diagnosis and monitoring of the disease. In the past years, spinal cord MRI has improved significantly and has become an important part of the diagnostic workup for MS. Presently, follow-up imaging of the spinal cord is only performed when spinal cord related symptoms occur. However, there is increasing evidence that asymptomatic spinal cord lesions can occur, independently of brain disease activity. Despite these cord lesions being asymptomatic, they impact disability accrual in the long term. Although this might be an imaging marker for monitoring and treatment, it is not yet applied in the clinical setting.\n\nThe investigators will prospectively collect spinal cord MRI data (in addition to routine brain MRI), and blood-based biomarkers (plus cerebral spinal fluid markers, if available), in recently diagnosed MS patients, to address the following research questions:\n\n* What is the incidence of asymptomatic spinal cord lesions in patients commencing DMT?\n* And in the absence of radiological progression on brain imaging, how frequently do asymptomatic spinal cord lesions occur? In other words, how often is disease activity solely proven by spinal cord MRI and what is the number-needed-to-scan?\n* A secondary objective is to investigate which patients are predisposed to developing new spinal cord lesions during follow-up in the early stages of the disease. For this question, factors such as cerebrospinal fluid (CSF) profiles, B-cell composition in blood, soluble blood markers, and clinical features will be focused on.', 'detailedDescription': 'The investigators aim to prospectively collect spinal cord MRI data (in addition to routine brain MRI), in recently diagnosed MS patients, to address the following research questions:\n\nWhat is the incidence of asymptomatic spinal cord lesions in patients commencing DMT?\n\nAnd in the absence of radiological progression on brain imaging, how frequently do asymptomatic spinal cord lesions occur? In other words, how often is disease activity solely proven by spinal cord MRI and what is the number-needed-to-scan?\n\n1. What is the incidence of asymptomatic spinal cord lesions in patients commencing DMT?\n2. In the absence of radiological progression on brain imaging, how frequently do asymptomatic spinal cord lesions occur? In other words, how often is disease activity solely proven by spinal cord MRI and what is the number-needed-to-scan?\n\nHypothesis: The hypothesis is that the detected incidence of asymptomatic cord lesions independent of brain MRI activity will be higher than the approximately 10% per year reported in retrospective studies.\n\nA secondary objective is to investigate which patients are predisposed to developing new spinal cord lesions during follow-up in the early stages of the disease. For this question, factors such as cerebrospinal fluid (CSF) profiles, B-cell composition in blood, soluble blood markers, and clinical features will be focused on.\n\n2\\. What subgroups are prone to new spinal cord lesions at follow-up in early disease? In particular:\n\n* Can disease activity on spinal cord MRI be predicted by baseline CSF profiles, i.e. is there an association between intrathecal IgM/IgG synthesis, number of oligoclonal bands and/or kappa free light chains at baseline and formation of new spinal cord lesions at follow-up?\n* Is there an association between low number of transitional B cells in blood at baseline and formation of new spinal cord lesions?\n* Is there an association between soluble blood markers and other blood biomarkers at baseline and formation of new spinal cord lesions at follow-up?\n* What subtype of clinical presentation or certain physical complaints are associated with new spinal cord lesions during follow-up?\n\nHypothesis: The hypothesis is that more new spinal cord lesions occur in patients with CSF profile positive for intrathecal IgM, IgG synthesis and higher number oligoclonal bands, a low number of transitional B cells at baseline, a low number of CD56bright NK cells, high levels of activating sICPs and low levels of inhibitory sICPs at baseline, and/or a presenting syndrome of optic neuritis or myelitis.\n\nTo investigate the research questions, MS patients will be enrolled from five Dutch MS centres in an observational study with a follow-up of 27 months. Patients will be asked to participate when they are being screened for DMT initiation and given 7 days to consider. Informed consent will be obtained by a doctor, part of the research team. Next to routine regular follow-up with brain MRI and outpatient clinic visits, patients will receive spinal cord MRI and a structured registration of clinical parameters and collection of blood samples. Towards the end of follow-up, it will be evaluated whether starting an extension study is of additional value.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'maximumAge': '65 Years', 'minimumAge': '18 Years', 'samplingMethod': 'NON_PROBABILITY_SAMPLE', 'studyPopulation': 'Population of treatment-naïve relapsing-remitting MS patients, early in the disease course (within 5 years of first clinical event) between 18 - 65 years old, where a first DMT is initiated.', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Patients between 18 and 65 years old\n* Patients diagnosed with relapsing-remitting MS (≤5 years of first clinical event)\n* Treatment-naïve patients starting (currently in the Netherlands approved) DMT\n\nExclusion Criteria:\n\n* Patients who presented first clinical event more than five years ago\n* Patients who have already started DMT\n* Patients who are incapable of giving informed consent\n* Patients who are unable to undergo local MRI scan, due to for instance\n* Physical problems, for instance due to size/obesity (not fitting in regular MRI scanner), not being able to lie flat for extended periods of time (e.g. due to pain, shortness of breath)\n* Due to claustrophobia\n* Patients who have contraindications for MRI scan, for instance\n* Due to MRI-unsafe or non-compatible implanted material/devices, such as pacemakers or ocular metal splinters\n* Patients who are pregnant at inclusion'}, 'identificationModule': {'nctId': 'NCT06827834', 'acronym': 'MSpine', 'briefTitle': 'Spinal Cord Monitoring in Multiple Sclerosis', 'organization': {'class': 'OTHER', 'fullName': 'Zuyderland Medisch Centrum'}, 'officialTitle': 'A Prospective Longitudinal Study of Spinal Cord Lesions in Multiple Sclerosis: MRI Monitoring and Prognostic Factors for Active Disease', 'orgStudyIdInfo': {'id': 'Z2023148'}}, 'contactsLocationsModule': {'locations': [{'zip': '6815AD', 'city': 'Arnhem', 'state': 'Gelderland', 'status': 'NOT_YET_RECRUITING', 'country': 'Netherlands', 'contacts': [{'name': 'Tom Olde Dubbelink', 'role': 'CONTACT', 'email': 'toldedubbelink@rijnstate.nl', 'phone': '+31880058888'}, {'name': 'Tom Olde Dubbelink', 'role': 'PRINCIPAL_INVESTIGATOR'}], 'facility': 'Rijnstate', 'geoPoint': {'lat': 51.98, 'lon': 5.91111}}, {'zip': '6162BG', 'city': 'Geleen', 'state': 'Limburg', 'status': 'RECRUITING', 'country': 'Netherlands', 'contacts': [{'name': 'Demmie Bouweriks, MD', 'role': 'CONTACT', 'email': 'd.bouweriks@zuyderland.nl', 'phone': '+31884597603'}, {'name': 'Oliver Gerlach', 'role': 'PRINCIPAL_INVESTIGATOR'}], 'facility': 'Zuyderland Medisch Centrum', 'geoPoint': {'lat': 50.97417, 'lon': 5.82917}}, {'zip': '5223GZ', 'city': "'s-Hertogenbosch", 'state': 'North Brabant', 'status': 'NOT_YET_RECRUITING', 'country': 'Netherlands', 'contacts': [{'name': 'Jeroen van Eijk', 'role': 'CONTACT', 'email': 'j.eijkvan@jbz.nl', 'phone': '+31735532325'}, {'name': 'Jeroen van Eijk', 'role': 'PRINCIPAL_INVESTIGATOR'}], 'facility': 'Jeroen Bosch Ziekenhuis', 'geoPoint': {'lat': 51.69917, 'lon': 5.30417}}, {'zip': '3318AT', 'city': 'Dordrecht', 'state': 'South Holland', 'status': 'RECRUITING', 'country': 'Netherlands', 'contacts': [{'name': 'Janet de Beukelaar', 'role': 'CONTACT', 'email': 'beukelaarj@asz.nl', 'phone': '+31786541111'}, {'name': 'Janet de Beukelaar', 'role': 'PRINCIPAL_INVESTIGATOR'}], 'facility': 'Albert Schweitzer ziekenhuis', 'geoPoint': {'lat': 51.81, 'lon': 4.67361}}, {'zip': '3015GD', 'city': 'Rotterdam', 'state': 'South Holland', 'status': 'NOT_YET_RECRUITING', 'country': 'Netherlands', 'contacts': [{'name': 'Joost Smolders', 'role': 'CONTACT', 'email': 'j.j.f.m.smolders@erasmusmc.nl', 'phone': '+31107040130'}, {'name': 'Joost Smolders', 'role': 'PRINCIPAL_INVESTIGATOR'}], 'facility': 'Erasmus MC', 'geoPoint': {'lat': 51.9225, 'lon': 4.47917}}], 'centralContacts': [{'name': 'Demmie Bouweriks, MD', 'role': 'CONTACT', 'email': 'd.bouweriks@zuyderland.nl', 'phone': '+31884597603'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Zuyderland Medisch Centrum', 'class': 'OTHER'}, 'responsibleParty': {'type': 'SPONSOR'}}}}