Ignite Creation Date:
2025-12-24 @ 11:43 PM
Ignite Modification Date:
2025-12-31 @ 6:11 PM
Study NCT ID:
NCT06593951
Status:
RECRUITING
Last Update Posted:
2024-10-15
First Post:
2024-09-10
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Registry and Natural History Study for Progressive Myoclonus Epilepsy Type 1 (EPM1)
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D020191', 'term': 'Myoclonic Epilepsies, Progressive'}, {'id': 'D020194', 'term': 'Unverricht-Lundborg Syndrome'}, {'id': 'D009207', 'term': 'Myoclonus'}], 'ancestors': [{'id': 'D004831', 'term': 'Epilepsies, Myoclonic'}, {'id': 'D004829', 'term': 'Epilepsy, Generalized'}, {'id': 'D004827', 'term': 'Epilepsy'}, {'id': 'D001927', 'term': 'Brain Diseases'}, {'id': 'D002493', 'term': 'Central Nervous System Diseases'}, {'id': 'D009422', 'term': 'Nervous System Diseases'}, {'id': 'D000073376', 'term': 'Epileptic Syndromes'}, {'id': 'D020271', 'term': 'Heredodegenerative Disorders, Nervous System'}, {'id': 'D019636', 'term': 'Neurodegenerative Diseases'}, {'id': 'D030342', 'term': 'Genetic Diseases, Inborn'}, {'id': 'D009358', 'term': 'Congenital, Hereditary, and Neonatal Diseases and Abnormalities'}, {'id': 'D020820', 'term': 'Dyskinesias'}, {'id': 'D009461', 'term': 'Neurologic Manifestations'}, {'id': 'D012816', 'term': 'Signs and Symptoms'}, {'id': 'D013568', 'term': 'Pathological Conditions, Signs and Symptoms'}]}}, 'protocolSection': {'designModule': {'bioSpec': {'retention': 'SAMPLES_WITH_DNA', 'description': 'Blood and / or urine samples'}, 'studyType': 'OBSERVATIONAL', 'designInfo': {'timePerspective': 'PROSPECTIVE', 'observationalModel': 'COHORT'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 200}, 'targetDuration': '5 Years', 'patientRegistry': True}, 'statusModule': {'overallStatus': 'RECRUITING', 'startDateStruct': {'date': '2024-10-10', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2024-10', 'completionDateStruct': {'date': '2030-10-01', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2024-10-10', 'studyFirstSubmitDate': '2024-09-10', 'studyFirstSubmitQcDate': '2024-09-10', 'lastUpdatePostDateStruct': {'date': '2024-10-15', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2024-09-19', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2029-10-01', 'type': 'ESTIMATED'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Unified Myoclonus Rating Scale (UMRS)', 'timeFrame': '5 years', 'description': 'Perform longitudinal Unified Myoclonus Rating Scale (UMRS) assessments and clinical interviews via video-teleconference in EPM1 patients to track functional impairment and disease progression.'}, {'measure': 'Creation of Biorepository', 'timeFrame': '5 years', 'description': 'Establish a biobank for patients with CSTB mutations, including EPM1 and CSTB-null disease, enabling quantitative profiling of biochemical biomarkers.'}, {'measure': 'Assess Health-Related Quality of Life', 'timeFrame': '5 years', 'description': 'Conduct a health-related quality of life survey on EPM1 and CSTB-null disease patients to understand the priorities of and impact on patients and caregivers.'}], 'secondaryOutcomes': [{'measure': 'Establish clinical trial readiness', 'timeFrame': '5 years', 'description': 'To facilitate an early diagnosis, enable counseling and anticipatory guidance of affected families and help define clinically meaningful endpoints for future interventional trials.'}]}, 'oversightModule': {'oversightHasDmc': False, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['Myoclonus', 'Progressive Myoclonus', 'CSTB', 'Non-epileptic action-induced myoclonus', 'Non-epileptic stimulus-induced myoclonus', 'Cerebellar disfunction', 'EPM1'], 'conditions': ['Progressive Myoclonus Epilepsy Type 1', 'EPM1', 'CSTB-related Disease', 'Myoclonus Epilepsies, Progressive', 'Unverricht-Lundborg Disease', 'Progressive Epilepsy and/or Ataxia With Myoclonus as a Major Feature', 'PME', 'Progressive Myoclonus-Epilepsies']}, 'referencesModule': {'references': [{'pmid': '34454274', 'type': 'BACKGROUND', 'citation': 'Rissanen SM, Hypponen J, Silvennoinen K, Saisanen L, Karjalainen PA, Mervaala E, Kalviainen R. Wearable monitoring of positive and negative myoclonus in progressive myoclonic epilepsy type 1. Clin Neurophysiol. 2021 Oct;132(10):2464-2472. doi: 10.1016/j.clinph.2021.06.026. Epub 2021 Jul 30.'}, {'pmid': '18028412', 'type': 'BACKGROUND', 'citation': 'Joensuu T, Lehesjoki AE, Kopra O. Molecular background of EPM1-Unverricht-Lundborg disease. Epilepsia. 2008 Apr;49(4):557-63. doi: 10.1111/j.1528-1167.2007.01422.x. Epub 2007 Nov 19.'}, {'pmid': '35195898', 'type': 'BACKGROUND', 'citation': 'Hadady L, Klivenyi P, Fabo D, Beniczky S. Real-world user experience with seizure detection wearable devices in the home environment. Epilepsia. 2023 Dec;64 Suppl 4:S72-S77. doi: 10.1111/epi.17189. Epub 2022 Feb 23.'}, {'pmid': '27053715', 'type': 'BACKGROUND', 'citation': 'Hainque E, Vidailhet M, Cozic N, Charbonnier-Beaupel F, Thobois S, Tranchant C, Brochard V, Glibert G, Drapier S, Mutez E, Doe De Maindreville A, Lebouvier T, Hubsch C, Degos B, Bonnet C, Grabli D, Legrand AP, Meneret A, Azulay JP, Bissery A, Zahr N, Clot F, Mallet A, Dupont S, Apartis E, Corvol JC, Roze E. A randomized, controlled, double-blind, crossover trial of zonisamide in myoclonus-dystonia. Neurology. 2016 May 3;86(18):1729-35. doi: 10.1212/WNL.0000000000002631. Epub 2016 Apr 6.'}, {'pmid': '37198334', 'type': 'BACKGROUND', 'citation': 'Mullard A. NfL makes regulatory debut as neurodegenerative disease biomarker. Nat Rev Drug Discov. 2023 Jun;22(6):431-434. doi: 10.1038/d41573-023-00083-z. No abstract available.'}, {'pmid': '34754043', 'type': 'BACKGROUND', 'citation': 'Nasseri M, Pal Attia T, Joseph B, Gregg NM, Nurse ES, Viana PF, Worrell G, Dumpelmann M, Richardson MP, Freestone DR, Brinkmann BH. Ambulatory seizure forecasting with a wrist-worn device using long-short term memory deep learning. Sci Rep. 2021 Nov 9;11(1):21935. doi: 10.1038/s41598-021-01449-2.'}, {'pmid': '25327891', 'type': 'BACKGROUND', 'citation': 'Okuneva O, Korber I, Li Z, Tian L, Joensuu T, Kopra O, Lehesjoki AE. Abnormal microglial activation in the Cstb(-/-) mouse, a model for progressive myoclonus epilepsy, EPM1. Glia. 2015 Mar;63(3):400-11. doi: 10.1002/glia.22760. Epub 2014 Oct 18.'}, {'pmid': '28378817', 'type': 'BACKGROUND', 'citation': "O'Brien A, Marshall CR, Blaser S, Ray PN, Yoon G. Severe neurodegeneration, progressive cerebral volume loss and diffuse hypomyelination associated with a homozygous frameshift mutation in CSTB. Eur J Hum Genet. 2017 Jun;25(6):775-778. doi: 10.1038/ejhg.2017.39. Epub 2017 Apr 5."}, {'pmid': '26843564', 'type': 'BACKGROUND', 'citation': 'Mancini GM, Schot R, de Wit MC, de Coo RF, Oostenbrink R, Bindels-de Heus K, Berger LP, Lequin MH, de Vries FA, Wilke M, van Slegtenhorst MA. CSTB null mutation associated with microcephaly, early developmental delay, and severe dyskinesia. Neurology. 2016 Mar 1;86(9):877-8. doi: 10.1212/WNL.0000000000002422. Epub 2016 Feb 3. No abstract available.'}, {'pmid': '1673790', 'type': 'BACKGROUND', 'citation': 'Lehesjoki AE, Koskiniemi M, Sistonen P, Miao J, Hastbacka J, Norio R, de la Chapelle A. Localization of a gene for progressive myoclonus epilepsy to chromosome 21q22. Proc Natl Acad Sci U S A. 1991 May 1;88(9):3696-9. doi: 10.1073/pnas.88.9.3696.'}, {'pmid': '26666500', 'type': 'BACKGROUND', 'citation': 'Kalviainen R, Genton P, Andermann E, Andermann F, Magaudda A, Frucht SJ, Schlit AF, Gerard D, de la Loge C, von Rosenstiel P. Brivaracetam in Unverricht-Lundborg disease (EPM1): Results from two randomized, double-blind, placebo-controlled studies. Epilepsia. 2016 Feb;57(2):210-21. doi: 10.1111/epi.13275. Epub 2015 Dec 15.'}, {'pmid': '12918016', 'type': 'BACKGROUND', 'citation': 'Houseweart MK, Pennacchio LA, Vilaythong A, Peters C, Noebels JL, Myers RM. Cathepsin B but not cathepsins L or S contributes to the pathogenesis of Unverricht-Lundborg progressive myoclonus epilepsy (EPM1). J Neurobiol. 2003 Sep 15;56(4):315-27. doi: 10.1002/neu.10253.'}, {'pmid': '38135787', 'type': 'BACKGROUND', 'citation': 'Gumusgoz E, Kasiri S, Verma M, Wu J, Villarreal Acha D, Marriam U, Fyffe-Maricich S, Lin A, Chen X, Gray SJ, Minassian BA. CSTB gene replacement improves neuroinflammation, neurodegeneration and ataxia in murine type 1 progressive myoclonus epilepsy. Gene Ther. 2024 May;31(5-6):234-241. doi: 10.1038/s41434-023-00433-x. Epub 2023 Dec 22.'}, {'pmid': '11571347', 'type': 'BACKGROUND', 'citation': 'Frucht SJ, Louis ED, Chuang C, Fahn S. A pilot tolerability and efficacy study of levetiracetam in patients with chronic myoclonus. Neurology. 2001 Sep 25;57(6):1112-4. doi: 10.1212/wnl.57.6.1112.'}, {'pmid': '11968461', 'type': 'BACKGROUND', 'citation': 'Frucht SJ, Leurgans SE, Hallett M, Fahn S. The Unified Myoclonus Rating Scale. Adv Neurol. 2002;89:361-76. No abstract available.'}, {'pmid': '32378798', 'type': 'BACKGROUND', 'citation': 'Di Matteo F, Pipicelli F, Kyrousi C, Tovecci I, Penna E, Crispino M, Chambery A, Russo R, Ayo-Martin AC, Giordano M, Hoffmann A, Ciusani E, Canafoglia L, Gotz M, Di Giaimo R, Cappello S. Cystatin B is essential for proliferation and interneuron migration in individuals with EPM1 epilepsy. EMBO Mol Med. 2020 Jun 8;12(6):e11419. doi: 10.15252/emmm.201911419. Epub 2020 May 7.'}, {'pmid': '34102276', 'type': 'BACKGROUND', 'citation': 'Daura E, Tegelberg S, Yoshihara M, Jackson C, Simonetti F, Aksentjeff K, Ezer S, Hakala P, Katayama S, Kere J, Lehesjoki AE, Joensuu T. Cystatin B-deficiency triggers ectopic histone H3 tail cleavage during neurogenesis. Neurobiol Dis. 2021 Aug;156:105418. doi: 10.1016/j.nbd.2021.105418. Epub 2021 Jun 5.'}, {'pmid': '27582036', 'type': 'BACKGROUND', 'citation': 'Crespel A, Ferlazzo E, Franceschetti S, Genton P, Gouider R, Kalviainen R, Korja M, Lehtinen MK, Mervaala E, Simonato M, Vaarmann A. Unverricht-Lundborg disease. Epileptic Disord. 2016 Sep 1;18(S2):28-37. doi: 10.1684/epd.2016.0841.'}, {'pmid': '33841303', 'type': 'BACKGROUND', 'citation': "Assenza G, Nocerino C, Tombini M, Di Gennaro G, D'Aniello A, Verrotti A, Marrelli A, Ricci L, Lanzone J, Di Lazzaro V, Bilo L, Coppola A. Perampanel Improves Cortical Myoclonus and Disability in Progressive Myoclonic Epilepsies: A Case Series and a Systematic Review of the Literature. Front Neurol. 2021 Mar 24;12:630366. doi: 10.3389/fneur.2021.630366. eCollection 2021."}, {'pmid': '37482941', 'type': 'BACKGROUND', 'citation': 'Alecu JE, Saffari A, Ziegler M, Jordan C, Tam A, Kim S, Leung E, Szczaluba K, Mierzewska H, King SD, Santorelli FM, Yoon G, Trombetta B, Kivisakk P, Zhang B, Sahin M, Ebrahimi-Fakhari D. Plasma Neurofilament Light Chain Is Elevated in Adaptor Protein Complex 4-Related Hereditary Spastic Paraplegia. Mov Disord. 2023 Sep;38(9):1742-1750. doi: 10.1002/mds.29524. Epub 2023 Jul 22.'}]}, 'descriptionModule': {'briefSummary': 'The Registry and Natural History Study for Progressive Myoclonus Epilepsy Type 1 (EPM1) is focused on gathering longitudinal clinical data as well as biological samples (blood and/or urine) from male and female patients, of all ages, who have a molecular diagnosis of EPM1or CSTB-null-related disease. Currently, there are no therapies that halt disease progression in any CSTB-related diseases, highlighting the urgency for translational research into this condition. The primary objective of the registry is to determine the natural history and genotype-phenotype correlations of disease-causing variants in EPM1 and CSTB-null-related disease.', 'detailedDescription': 'Progressive myoclonus-epilepsies (PME) are severe epilepsies that insinuate into the lives of previously healthy children or young adults, irrevocably intensify, and become intractable. Progressive Myoclonic Epilepsy type 1 (EPM1), also known as Unverricht-Lundborg disease (ULD), is the prototypical and most common PME. It is caused by bi-allelic variants in the CSTB gene. The phenotypic spectrum of EPM1 is broad and reflects the amount of residual CSTB protein function in an individual. Individuals with classic EPM1 typically develop seizures between 6-16 years of age, followed by progressive non-epileptic action- and stimulus-induced myoclonus, ataxia, and cerebellar dysfunction with speech and swallowing impairment. These individuals generally have one or both CSTB variants partially functional. On the severe end of the spectrum are patients with a complete loss of the CSTB protein due to bi-allelic null variants.\n\nThe characterization of disease progression and biomarker discovery are necessary to define clinically meaningful endpoints for future interventional trials and to meet regulatory requirements for phase 1/2 and later-stage trials.\n\nAs an ultra-rare disease, patients with EPM1 are dispersed across the United States, making on-site visits for natural history studies burdensome to families. In this study, we will overcome this obstacle by adapting a remote- assessment-driven natural history study with clinical, electrophysiological, and biochemical biomarkers. The proposed study will delineate the natural history and evolution of myoclonus as a key disease feature in EPM1 and CSTB-related disease, will create a biobank for biospecimen, and will assess health-related quality of life. This approach will further clinical trial readiness for EPM1-related disease.\n\nSpecifically, the objectives of this protocol are to:\n\n1. Determine the natural history and genotype-phenotype correlations of disease-causing variants in EPM1-related disease.\n2. Facilitate an early diagnosis, enable counseling with anticipatory guidance of affected families and help define clinically meaningful endpoints for future interventional traits.\n\nSpecific aims include:\n\n1. Perform longitudinal Unified Myoclonus Rating Scale (UMRS) assessments and clinical interviews via video-teleconference with study participants to track functional impairment and disease progression.\n2. Establish a biobank for samples from participants with CSTB mutations, including EPM1 and CSTB-null disease, enabling quantitative profiling of biochemical biomarkers.\n3. Conduct a health-related quality of life survey about participants with EPM1 and CSTB-null disease to understand the impact on patients and caregivers.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['CHILD', 'ADULT', 'OLDER_ADULT'], 'samplingMethod': 'NON_PROBABILITY_SAMPLE', 'studyPopulation': 'The study population consists of male and female patients of all ages with a clinical and molecular diagnosis of EPM1-related disease.\n\nThe initial phase of this study will enroll a minimum of 10 individuals with EPM1-related disease. A total of 200 individuals may be entered in the study.', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Molecular diagnosis of EPM1-related disease\n* Access to web-based communication, including video-teleconference\n* Permanent address in the United States\n\nExclusion Criteria:\n\n* Not having such a diagnosis of EPM1-related disease.'}, 'identificationModule': {'nctId': 'NCT06593951', 'acronym': 'EPM1', 'briefTitle': 'Registry and Natural History Study for Progressive Myoclonus Epilepsy Type 1 (EPM1)', 'organization': {'class': 'OTHER', 'fullName': "Boston Children's Hospital"}, 'officialTitle': 'Registry and Natural History Study for Progressive Myoclonus Epilepsy Type 1 (EPM1)', 'orgStudyIdInfo': {'id': 'IRB-P00048807'}}, 'contactsLocationsModule': {'locations': [{'zip': '02115', 'city': 'Boston', 'state': 'Massachusetts', 'status': 'RECRUITING', 'country': 'United States', 'contacts': [{'name': 'Darius Ebrahimi-Fakhari, MD, PhD.', 'role': 'CONTACT', 'email': 'movementdisorders@childrens.harvard.edu', 'phone': '617-355-0097'}, {'name': 'Joshua Rong, BS', 'role': 'CONTACT', 'email': 'movementdisorders@childrens.harvard.edu'}], 'facility': 'Boston Childrens Hospital', 'geoPoint': {'lat': 42.35843, 'lon': -71.05977}}], 'centralContacts': [{'name': 'Darius Ebrahimi-Fakhari, MD, PhD.', 'role': 'CONTACT', 'email': 'movementdisorders@childrens.harvard.edu', 'phone': '617-355-0097'}, {'name': 'Joshua Rong, BS.', 'role': 'CONTACT', 'email': 'movementdisorders@childrens.harvard.edu', 'phone': '617-355-0903'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': "Boston Children's Hospital", 'class': 'OTHER'}, 'collaborators': [{'name': 'Epilepsy Foundation', 'class': 'OTHER'}], 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'Darius Ebrahimi-Fakhari, MD, PhD', 'investigatorFullName': 'Darius Ebrahimi-Fakhari', 'investigatorAffiliation': "Boston Children's Hospital"}}}}