Quantifying Disease Progression in LBSL

NCT05750979 | Unknown

• 1 other identifier: LBSL
• Study Type: observational
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

Leukoencephalopathy with brain stem involvement and lactate elevation (LBSL) is a genetic disorder caused by biallelic mutations in the DARS2 gene that encodes mitochondrial aspartyl tRNA synthase.(1, 2) It is characterized by typical abnormalities on MRI of the brain and spinal cord.(3) Clinically, the disorder is heterogeneous and can present in the neonatal period, later in childhood or even in adults.(3) In general it can be stated that the earlier presentations are characterized by rapid progression leading to severe disability and death. Presentation at a later age is typically characterized by a more benign disease course, although considerable disability is common. Clinically, the disease presents as a slowly progressive myelopathy with mainly involvement of the corticospinal tracts and the dorsal columns. Although the natural history has been studied in large cohorts, the rate of progression has not been systematically studied with clinimetric outcome scales or potential surrogate outcomes for spinal cord disease.

Conditions

LBSL; Leukoencephalopathies

Outcome Measures

Primary Outcomes (1)

• The primary outcome is disease progression on all parameters

  disease progression

  5 years

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

LBSL patients and healthy age-matched controls.

In order to be eligible to participate in this study, a subject must meet all of the following criteria: * Age \> 16 years * Definite diagnosis of LBSL confirmed by DARS2 mutation analysis. * Able to understand Dutch or English and provide informed consent. * No contra-indications for MRI of brain and spinal cord. Subjects eligible to participate as healthy controls must meet all of the following criteria: * Willing to visit the hospital * 16 years or older * Provision of written informed consent to participate in the study obtained from the participant For the MRI controls: \- No contra-indications for MRI of the brain and spinal cord A potential subject (patient or healthy control) who meets any of the following criteria will be excluded from participation in this study: * Unable to visit the hospital for the follow-up visits * Co-existing neurological disease that can cause pyramidal tract signs making interpretation of acquired data difficult (for instance, multiple sclerosis, stroke, etc)

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• M. Engelen: lead

Study Sites (1)

Amsterdam UMC

Amsterdam-Zuidoost, North Holland, 1105AZ, Netherlands

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

Plasma Leukocytes PAXGene for RNA storage

MeSH Terms

Conditions

Leukoencephalopathies

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Study Officials

• M. Engelen, Dr

  Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Marije Voermans

CONTACT

+31205668227; m.m.voermans@amsterdamumc.nl

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: February 18, 2023
• First Posted: March 2, 2023
• Study Start: March 11, 2021
• Primary Completion: December 31, 2025
• Study Completion: December 31, 2025
• Last Updated: March 2, 2023

Record last verified: 2023-02

Locations

NL (1)