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

NCT ID: NCT06593951

Last Updated: 2024-10-15

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 200 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2024-10-10
• Study Completion Date: 2030-10-01

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.

Detailed Description

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.

The 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.

As 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.

Specifically, the objectives of this protocol are to:

1. Determine the natural history and genotype-phenotype correlations of disease-causing variants in EPM1-related disease.

2. Facilitate an early diagnosis, enable counseling with anticipatory guidance of affected families and help define clinically meaningful endpoints for future interventional traits.

Specific aims include:

1. Perform longitudinal Unified Myoclonus Rating Scale (UMRS) assessments and clinical interviews via video-teleconference with study participants to track functional impairment and disease progression.

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

3. Conduct a health-related quality of life survey about participants with EPM1 and CSTB-null disease to understand the impact on patients and caregivers.

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

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Eligibility Criteria

Inclusion Criteria

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

Exclusion Criteria

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

• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Epilepsy Foundation

OTHER

Sponsor Role: collaborator

Boston Children's Hospital

OTHER

Sponsor Role: lead

Responsible Party

Darius Ebrahimi-Fakhari

Darius Ebrahimi-Fakhari, MD, PhD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Boston Childrens Hospital

Boston, Massachusetts, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Darius Ebrahimi-Fakhari, MD, PhD.

Role: CONTACT

movementdisorders@childrens.harvard.edu

617-355-0097

Joshua Rong, BS.

Role: CONTACT

movementdisorders@childrens.harvard.edu

617-355-0903

Facility Contacts

Darius Ebrahimi-Fakhari, MD, PhD.

Role: primary

movementdisorders@childrens.harvard.edu

617-355-0097

Joshua Rong, BS

Role: backup

movementdisorders@childrens.harvard.edu

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Other Identifiers

IRB-P00048807

Identifier Type: -

Identifier Source: org_study_id