## Protocol Section
### Identification Module
**NCT ID:** NCT05750979

**Acronym:** LBSL

**Brief Title:** Quantifying Disease Progression in LBSL

**Official Title:** Quantifying Disease Progression in Leukoencephalopathy With Brainstem and Spinal Cord Involvement and Lactate Elevation (LBSL)

#### Organization Study ID Info
**ID:** LBSL
#### Organization
**Class:** OTHER
**Full Name:** Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
### Status Module
#### Completion Date
**Date:** 2025-12-31

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2023-03-02

**Type:** ACTUAL

**Last Update Submit Date:** 2023-02-28

**Overall Status:** RECRUITING

#### Primary Completion Date
**Date:** 2025-12-31

**Type:** ESTIMATED

#### Start Date
**Date:** 2021-03-11

**Type:** ACTUAL

**Status Verified Date:** 2023-02

#### Study First Post Date
**Date:** 2023-03-02
**Type:** ACTUAL
**Study First Submit Date:** 2023-02-18
**Study First Submit QC Date:** 2023-02-28
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** OTHER

**Name:** M. Engelen

#### Responsible Party

**Investigator Affiliation:** Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

**Investigator Full Name:** M. Engelen

**Investigator Title:** Principal Investigator

**Type:** SPONSOR_INVESTIGATOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** False

**Oversight Has DMC:** False

### Description Module

**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 Module

**Conditions:**

- LBSL

- Leukoencephalopathies

### Design Module

#### Bio Spec

**Description:** Plasma Leukocytes PAXGene for RNA storage

**Retention:** SAMPLES_WITH_DNA

#### Design Info

**Observational Model:** COHORT

**Time Perspective:** PROSPECTIVE

#### Enrollment Info

**Count:** 20

**Type:** ESTIMATED

**Study Type:** OBSERVATIONAL

### Outcomes Module

#### Primary Outcomes

**Description:** disease progression

**Measure:** The primary outcome is disease progression on all parameters

**Time Frame:** 5 years

### Eligibility Module

**Eligibility Criteria:** 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)

**Healthy Volunteers:** True

**Minimum Age:** 16 Years

**Sampling Method:** NON_PROBABILITY_SAMPLE

**Sex:** ALL

**Standard Ages:**

- CHILD

- ADULT

- OLDER_ADULT

**Study Population:** LBSL patients and healthy age-matched controls.

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** m.m.voermans@amsterdamumc.nl

**Name:** Marije Voermans

**Phone:** +31205668227

**Role:** CONTACT

#### Locations

**Location 1:**

**City:** Amsterdam-Zuidoost

**Contacts:**

***Contact 1:***

- **Email:** m.m.voermans@amsterdamumc.nl

- **Name:** Marije Voermans, RN

- **Phone:** 0205668227

- **Role:** CONTACT

**Country:** Netherlands

**Facility:** Amsterdam UMC

**State:** Noord-Holland

**Status:** RECRUITING

**Zip:** 1105AZ

#### Overall Officials

**Official 1:**

**Affiliation:** Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

**Name:** M. Engelen, Dr

**Role:** PRINCIPAL_INVESTIGATOR

### IPD Sharing Statement Module

**IPD Sharing:** UNDECIDED

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000020969

- Term: Disease Attributes

- ID: D000010335

- Term: Pathologic Processes

- ID: D000001927

- Term: Brain Diseases

- ID: D000002493

- Term: Central Nervous System Diseases

- ID: D000009422

- Term: Nervous System Diseases

### Condition Browse Module - Browse Branches

- Abbrev: BC23

- Name: Symptoms and General Pathology

- Abbrev: All

- Name: All Conditions

- Abbrev: BC10

- Name: Nervous System Diseases

### Condition Browse Module - Browse Leaves

- ID: M20559

- Name: Disease Progression

- Relevance: HIGH

- As Found: Disease Progression

- ID: M28591

- Name: Leukoencephalopathies

- Relevance: HIGH

- As Found: Leukoencephalopathy

- ID: M22700

- Name: Disease Attributes

- Relevance: LOW

- As Found: Unknown

- ID: M5204

- Name: Brain Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M5742

- Name: Central Nervous System Diseases

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000056784

- Term: Leukoencephalopathies

- ID: D000018450

- Term: Disease Progression

### Misc Info Module

- Version Holder: 2024-05-24
