Registry and Natural History Study for Progressive Myoclonus Epilepsy Type 1 (EPM1)

NCT06593951 | Recruiting

• 1 other identifier: IRB-P00048807
• Study Type: observational
• Target: 200
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

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; Progressive Myoclonus Epilepsy Type 1

Keywords

Myoclonus; Progressive Myoclonus; CSTB; Non-epileptic action-induced myoclonus; Non-epileptic stimulus-induced myoclonus; Cerebellar disfunction; EPM1

Outcome Measures

Primary Outcomes (3)

• Unified Myoclonus Rating Scale (UMRS)

  Perform longitudinal Unified Myoclonus Rating Scale (UMRS) assessments and clinical interviews via video-teleconference in EPM1 patients to track functional impairment and disease progression.

  5 years

• Creation of Biorepository

  Establish a biobank for patients with CSTB mutations, including EPM1 and CSTB-null disease, enabling quantitative profiling of biochemical biomarkers.

  5 years

• Assess Health-Related Quality of Life

  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.

  5 years

Secondary Outcomes (1)

• Establish clinical trial readiness

  5 years

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

The study population consists of male and female patients of all ages with a clinical and molecular diagnosis of EPM1-related disease. The 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.

You may qualify if:

• Molecular diagnosis of EPM1-related disease
• Access to web-based communication, including video-teleconference
• Permanent address in the United States

You may not qualify if:

• Not having such a diagnosis of EPM1-related disease.

Sponsors & Collaborators

• Boston Children's Hospital: lead
• Epilepsy Foundation: collaborator

Study Sites (1)

Boston Childrens Hospital

Boston, Massachusetts, 02115, United States

RECRUITING

Related Publications (20)

• 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: 34454274 BACKGROUND

• 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: 18028412 BACKGROUND

• 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: 35195898 BACKGROUND

• 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: 27053715 BACKGROUND

• 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: 37198334 BACKGROUND

• 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: 34754043 BACKGROUND

• 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: 25327891 BACKGROUND

• 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: 28378817 BACKGROUND

• 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: 26843564 BACKGROUND

• 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: 1673790 BACKGROUND

• 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: 26666500 BACKGROUND

• 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: 12918016 BACKGROUND

• 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: 38135787 BACKGROUND

• 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: 11571347 BACKGROUND

• Frucht SJ, Leurgans SE, Hallett M, Fahn S. The Unified Myoclonus Rating Scale. Adv Neurol. 2002;89:361-76. No abstract available.

  PMID: 11968461 BACKGROUND

• 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: 32378798 BACKGROUND

• 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: 34102276 BACKGROUND

• 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: 27582036 BACKGROUND

• 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: 33841303 BACKGROUND

• 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.

  PMID: 37482941 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Blood and / or urine samples

MeSH Terms

Conditions

Myoclonic Epilepsies, Progressive; Unverricht-Lundborg Syndrome; Myoclonus

Condition Hierarchy (Ancestors)

Epilepsies, Myoclonic; Epilepsy, Generalized; Epilepsy; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Epileptic Syndromes; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Dyskinesias; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Central Study Contacts

Darius Ebrahimi-Fakhari, MD, PhD.

CONTACT

617-355-0097; movementdisorders@childrens.harvard.edu

Joshua Rong, BS.

CONTACT

617-355-0903; movementdisorders@childrens.harvard.edu

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 5 Years
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Darius Ebrahimi-Fakhari, MD, PhD

Study Record Dates

• First Submitted: September 10, 2024
• First Posted: September 19, 2024
• Study Start: October 10, 2024
• Primary Completion (Estimated): October 1, 2029
• Study Completion (Estimated): October 1, 2030
• Last Updated: March 18, 2026

Record last verified: 2026-03

Locations

US (1)