Clinical trial NCT03624374: Natural History Study of Leukoencephalopathy With Brainstem and Spinal Cord Involvement and Lactate Elevation (LBSL)
Official title: Characterization of the Natural History of Leukoencephalopathy With Brainstem and Spinal Cord Involvement and Lactate Elevation
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Leukoencephalopathies
LBSL
Leukoencephalopathy With Brainstem and Spinal Cord Involvement and Lactate Elevation
White Matter Disease
Ataxia, Cerebellar
Genetic Disease
Keywords: Natural History Study
Kennedy Krieger Institute
Virtual assessment
DARS2
Johns Hopkins Hospital
Lead sponsor: Hugo W. Moser Research Institute at Kennedy Krieger, Inc.
Sponsor class: OTHER
First posted: 2018-08-10
Enrollment: 100
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: All case subjects will be known to have leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation.

Brief summary: In this study, we will conduct retrospective chart and imaging reviews and prospective longitudinal virtual assessments of individuals with LBSL.

Detailed description: LBSL (leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation) is a rare genetic disorder characterized by slowly progressive cerebellar ataxia and spasticity with dorsal column dysfunction (decreased position and vibration sense) in most patients. Manual dexterity becomes impaired to a variable degree. Associated problems include dysarthria, mild cognitive decline and learning problems, and epilepsy. LBSL is diagnosed by identification of biallelic pathogenic variants in DARS2, encoding mitochondrial aspartyl tRNA synthetase and characteristic abnormalities observed on the brain and spinal cord MRI. Most of the literature consists of case reports and case series and there are only limited data that provide details on genotype-phenotype correlations. There is very little quantitative or semi-quantitative information about neurocognitive and neuromotor impairment in LBSL. There are currently no targeted therapies or guidelines about supportive therapies for LBSL.

In this study, we will conduct retrospective chart and imaging reviews and prospective longitudinal virtual assessments of individuals with LBSL.

We hypothesize that 1) there will be a broad phenotypic spectrum of neuromotor and neurocognitive deficits in LBSL patients; 2) most impairment will likely be related to gait; 3) there will be a threshold of impairment in gait that is associated with poorer quality of life for these patients; 4) and that even in patients with apparently mild disease there will be neurocognitive deficits related to cortical and cerebellar white matter abnormalities.

Answering these hypotheses will form the basis of a better understanding of the natural history of LBSL. It will help further characterize the expected level of impairment based on a patient's genotype. This will be particularly helpful for providing anticipatory guidance for newly diagnosed infants and children with LBSL. The information will also help identify priorities for existing supportive therapies and help clarify the common or clinically meaningful symptoms that should be targeted for new treatments.

Eligibility criteria: Inclusion Criteria:

1. Confirmed DARS2 mutation through genetic analysis
2. Ability of the caregiver or participant to speak and understand English at an 8th-grade level

Exclusion Criteria:

* The vulnerable populations of prisoners, non-viable neonates, pregnant women, adults lacking the capacity to consent, non-English speakers or children who are in foster care or wards of the state.

Primary outcomes:
measure: Track Natural History of LBSL patients using medical record review
timeFrame: 4/1/2018 - 3/31/2023
measure: Assessment of behavior in patients with LBSL using standardized neurocognitive surveys.
timeFrame: 4/1/2018 - 3/31/2023
measure: Assessment of social communication in patients with LBSL using standardized neurocognitive surveys.
timeFrame: 4/1/2018 - 3/31/2023
measure: Assessment of executive function in patients with LBSL using standardized neurocognitive surveys.
timeFrame: 4/1/2018 - 3/31/2023
measure: Assessment of adaptive function in patients with LBSL using standardized neurocognitive surveys.
timeFrame: 4/1/2018 - 3/31/2023
measure: Assessment of quality of life in patients with LBSL using standardized surveys.
timeFrame: 4/1/2018 - 3/31/2023
measure: Assessment of ataxia in patients with LBSL using wearable sensor technology and standardized clinical scales.
timeFrame: 4/1/2018 - 3/31/2023
measure: Assessment of balance in patients with LBSL using wearable sensor technology.
timeFrame: 4/1/2018 - 3/31/2023
measure: Timed Up and Go Test
timeFrame: 4/1/2018 - 3/31/2023
measure: Long Walk Test
timeFrame: 4/1/2018 - 3/31/2023
Secondary outcomes:
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Hugo Moser Center for Leukodystrophies
state: Maryland
Study officials:
affiliation: Moser Center for Leukodystrophies at Kennedy Krieger Institute
name: Amena S Fine, MD PhD
role: PRINCIPAL_INVESTIGATOR
References: