Clinical trial NCT06593951: Registry and Natural History Study for Progressive Myoclonus Epilepsy Type 1 (EPM1)
Official title: Registry and Natural History Study for Progressive Myoclonus Epilepsy Type 1 (EPM1)
Study type: OBSERVATIONAL
Overall status: RECRUITING
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
Keywords: Myoclonus
Progressive Myoclonus
CSTB
Non-epileptic action-induced myoclonus
Non-epileptic stimulus-induced myoclonus
Cerebellar disfunction
EPM1
Lead sponsor: Boston Children's Hospital
Sponsor class: OTHER
Collaborators: name: Epilepsy Foundation
First posted: 2024-09-19
Enrollment: 200
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

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.

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.

Primary outcomes:
measure: Unified Myoclonus Rating Scale (UMRS)
timeFrame: 5 years
measure: Creation of Biorepository
timeFrame: 5 years
measure: Assess Health-Related Quality of Life
timeFrame: 5 years
Secondary outcomes:
measure: Establish clinical trial readiness
timeFrame: 5 years
Other outcomes:
Locations:
city: Boston
country: United States
facility: Boston Childrens Hospital
state: Massachusetts
Study officials:
References:
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