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

March 16, 2026 updated by: Darius Ebrahimi-Fakhari, Boston Children's Hospital

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.

Study Overview

Status

Recruiting

Conditions

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:

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

Perform longitudinal Unified Myoclonus Rating Scale (UMRS) assessments and clinical interviews via video-teleconference with study participants to track functional impairment and disease progression.
Establish a biobank for samples from participants with CSTB mutations, including EPM1 and CSTB-null disease, enabling quantitative profiling of biochemical biomarkers.
Conduct a health-related quality of life survey about participants with EPM1 and CSTB-null disease to understand the impact on patients and caregivers.

Study Type

Observational

Enrollment (Estimated)

200

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Name: Darius Ebrahimi-Fakhari, MD, PhD.
Phone Number: 617-355-0097
Email: movementdisorders@childrens.harvard.edu

Study Contact Backup

Name: Joshua Rong, BS.
Phone Number: 617-355-0903
Email: movementdisorders@childrens.harvard.edu

Study Locations

United States
- Massachusetts
  - Boston, Massachusetts, United States, 02115
    - Recruiting
    - Boston Childrens Hospital
    - Contact:
      
      Darius Ebrahimi-Fakhari, MD, PhD.
      
      Phone Number: 617-355-0097
      
      Email: movementdisorders@childrens.harvard.edu
    - Contact:
      
      Joshua Rong, BS
      
      Email: movementdisorders@childrens.harvard.edu

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

Child
Adult
Older Adult

Accepts Healthy Volunteers

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.

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Unified Myoclonus Rating Scale (UMRS) Time Frame: 5 years	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 Time Frame: 5 years	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 Time Frame: 5 years	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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Establish clinical trial readiness Time Frame: 5 years	To facilitate an early diagnosis, enable counseling and anticipatory guidance of affected families and help define clinically meaningful endpoints for future interventional trials.	5 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Boston Children's Hospital

Collaborators

Epilepsy Foundation

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 10, 2024

Primary Completion (Estimated)

October 1, 2029

Study Completion (Estimated)

October 1, 2030

Study Registration Dates

First Submitted

September 10, 2024

First Submitted That Met QC Criteria