LeukoencephalopathiesNCT03624374
Natural History Study of Leukoencephalopathy With Brainstem and Spinal Cord Involvement and Lactate Elevation (LBSL)
An observational study of Leukoencephalopathies and LBSL, run by Hugo W. Moser Research Institute at Kennedy Krieger, Inc. at 1 site in United States.
Trial summary
In this study, we will conduct retrospective chart and imaging reviews and prospective longitudinal virtual assessments of individuals with LBSL. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Leukoencephalopathies, LBSL, Leukoencephalopathy With Brainstem and Spinal Cord Involvement and Lactate Elevation
- How many people
- 100 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Apr 2018to May 2029
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: All case subjects will be known to have leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation.
Who may be able to join
- Confirmed DARS2 mutation through genetic analysis
- Ability of the caregiver or participant to speak and understand English at an 8th-grade level
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Hugo Moser Center for Leukodystrophies
Baltimore, Maryland, 21205
Connor Murray, 443-923-2750, murrayc@kennedykrieger.org
Ali Fatemi, MD MBA
About this study
Official title: Characterization of the Natural History of Leukoencephalopathy With Brainstem and Spinal Cord Involvement and Lactate Elevation
In this study, we will conduct retrospective chart and imaging reviews and prospective longitudinal virtual assessments of individuals with LBSL.
Read the 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.
- 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
- Medical subject headings
- Leukoencephalopathies, Leukoencephalopathy with Brainstem and Spinal Cord Involvement and Lactate Elevation, Cerebellar Ataxia, Genetic Diseases, Inborn
What is being measured
The primary outcome is the main question the study is designed to answer.
Track Natural History of LBSL patients using medical record review
Participants will be asked to provide all prior neurological, developmental and genetics medical records and available neuroimaging studies. We will first confirm eligibility by review of MRI and DARS2 mutation analysis. We will determine information about disease duration, rate of symptom progression and prevalence of specific neurological symptoms and the level of disability.
We have derived an MRI severity score by modifying a standard leukodystrophy MRI scoring system, referred to as the Loes severity score (developed by Dr. Daniel Loes). This score is routinely used by radiologists. We will be reviewing and scoring participant neuroimages to better understand correlation with disease severity and progression.
Measured: 4/1/2018 - 3/31/2023
Assessment of behavior in patients with LBSL using standardized neurocognitive surveys.
After the participant is enrolled, they will receive several neurocognitive assessments that will be sent digitally, including the Child or Adult Behavior Checklist (CBCL/ABCL). The CBCL/ABCL is one of most widely used measures in psychology to identify behavioral problems or mood disorders in children or adults, respectively. The scoring of this checklist is grouped by eight empirically based syndrome scales. These include aggressive behavior, anxious/depressed, attention problems, rule-breaking behavior, somatic complaints, social problems, thought problems, withdrawal/depression symptoms. The CBCL has standardized scores for children of the same gender and similar age and are interpreted as falling in the normal, borderline, or clinical range.
Measured: 4/1/2018 - 3/31/2023
Assessment of social communication in patients with LBSL using standardized neurocognitive surveys.
After the participant is enrolled, they will receive several neurocognitive assessments that will be sent digitally, including the Social Communication Questionnaire (SCQ) The SCQ used by the International Autism Network will be used to screen individuals for Autism Spectrum Disorder and is completed by a caregiver. The SCQ is a 40 item, parent report screening measure that identifies whether a child has the associated symptoms of autism spectrum disorder.
Measured: 4/1/2018 - 3/31/2023
Assessment of executive function in patients with LBSL using standardized neurocognitive surveys.
After the participant is enrolled, they will receive several neurocognitive assessments that will be sent digitally, including the Behavioral Rating Inventory of Executive Function (BRIEF).The BRIEF assesses impairment of executive function by evaluating eight clinical scales of executive function including inhibit, shift, emotional control, initiate, working memory, plan/organize, organization of materials, and monitor.The BRIEF exists for preschool children (2-5) and there are self-report versions for adolescents and adults.
Measured: 4/1/2018 - 3/31/2023
Assessment of adaptive function in patients with LBSL using standardized neurocognitive surveys.
After the participant is enrolled, they will receive several neurocognitive assessments that will be sent digitally, including the Adaptive Behavior Assessment System version 3 (ABAS-3). The ABAS-3 survey assesses eleven essential skill areas in 3 major adaptive domains including conceptual, social and practical, and assists in diagnosing various developmental, learning, and behavioral disabilities. This complete battery of adaptive skills can be administered across the life span for ages Birth-89 years.
Measured: 4/1/2018 - 3/31/2023
Assessment of quality of life in patients with LBSL using standardized surveys.
After the participant is enrolled, they will receive several quality of life assessments that will be sent digitally. Information on quality of life in LBSL will be collected using well-validated scales addressing physical, emotional, social and school functioning. Relevant scales include quality of life in children and adults with spasticity, quality of life in children and adults with ataxia, and quality of life in children and adults with chronic medical conditions.
Measured: 4/1/2018 - 3/31/2023
Assessment of ataxia in patients with LBSL using wearable sensor technology and standardized clinical scales.
The study team will collect information about ataxia using wearable sensors and by administering the Standardized Assessment and Rating of Ataxia (SARA) scale at participant's homes.
The SARA scale is an 8-item performance based scale that assesses upper and lower extremity ataxia. A total score of 0 indicates no ataxia and the maximum score of 40 indicates severe ataxia.
Measured: 4/1/2018 - 3/31/2023
Assessment of balance in patients with LBSL using wearable sensor technology.
The study team will collect information about gait and balance ability over time using functional surveys as well as wearable sensors to be used at the participant's homes.
This series of tests will require the participant to stand in several different poses for 2 trials of 30 seconds each to assess their balance. This will include standing with their eyes open and their feet apart and together, as well as with their eyes closed and their feet apart and together.
Measured: 4/1/2018 - 3/31/2023
Timed Up and Go Test
This test will require the participant to sit in a chair. When the participant is instructed to, they will stand up from the chair, walk 3 meters in a straight line, turn around and walk back to the chair. The test duration and variables such as walking and turning speed will be obtained.
Measured: 4/1/2018 - 3/31/2023
Long Walk Test
This test will require the participant to walk 22 feet in a straight line for a duration of 2 minutes. Variables such as walking and turning speed, stride length and step-to-step variability will be obtained.
Measured: 4/1/2018 - 3/31/2023
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Aug 2018
- Study start1 Apr 2018
- Primary completionMay 2029 (estimated)
- Study completionMay 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for LeukoencephalopathiesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Hugo W. Moser Research Institute at Kennedy Krieger, Inc.
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Amena S Fine, MD PhD, Principal investigator, Moser Center for Leukodystrophies at Kennedy Krieger Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03624374
- Sponsor's protocol ID
- IRB00150619
- Status last verified
- Jul 2024
- First submitted
- 7 Aug 2018
- Last updated
- 3 Jul 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 Jul 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Characterization of the Natural History of Leukoencephalopathy With Brainstem and Spinal Cord Involvement and Lactate Elevation
- ClinicalTrials.gov ID
- NCT03624374
- Acronym / sponsor ID
- IRB00150619
- 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
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- Hugo W. Moser Research Institute at Kennedy Krieger, Inc.University, hospital or other
- Study start
- 1 Apr 2018 (actual)
- Primary completion
- May 2029 (estimated)
- Study completion
- May 2029 (estimated)
- First posted
- 10 Aug 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- All case subjects will be known to have leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation.
Key inclusion criteria (2 listed)
- Confirmed DARS2 mutation through genetic analysis
- Ability of the caregiver or participant to speak and understand English at an 8th-grade level
Key exclusion criteria (1 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Track Natural History of LBSL patients using medical record review
Time frame: 4/1/2018 - 3/31/2023
Participants will be asked to provide all prior neurological, developmental and genetics medical records and available neuroimaging studies. We will first confirm eligibility by review of MRI and DARS2 mutation analysis. We will determine information about disease duration, rate of symptom progression and prevalence of specific neurological symptoms and the level of disability. We have derived an MRI severity score by modifying a standard leukodystrophy MRI scoring system, referred to as the Loes severity score (developed by Dr. Daniel Loes). This score is routinely used by radiologists. We will be reviewing and scoring participant neuroimages to better understand correlation with disease severity and progression.
Assessment of behavior in patients with LBSL using standardized neurocognitive surveys.
Time frame: 4/1/2018 - 3/31/2023
After the participant is enrolled, they will receive several neurocognitive assessments that will be sent digitally, including the Child or Adult Behavior Checklist (CBCL/ABCL). The CBCL/ABCL is one of most widely used measures in psychology to identify behavioral problems or mood disorders in children or adults, respectively. The scoring of this checklist is grouped by eight empirically based syndrome scales. These include aggressive behavior, anxious/depressed, attention problems, rule-breaking behavior, somatic complaints, social problems, thought problems, withdrawal/depression symptoms. The CBCL has standardized scores for children of the same gender and similar age and are interpreted as falling in the normal, borderline, or clinical range.
Assessment of social communication in patients with LBSL using standardized neurocognitive surveys.
Time frame: 4/1/2018 - 3/31/2023
After the participant is enrolled, they will receive several neurocognitive assessments that will be sent digitally, including the Social Communication Questionnaire (SCQ) The SCQ used by the International Autism Network will be used to screen individuals for Autism Spectrum Disorder and is completed by a caregiver. The SCQ is a 40 item, parent report screening measure that identifies whether a child has the associated symptoms of autism spectrum disorder.
Assessment of executive function in patients with LBSL using standardized neurocognitive surveys.
Time frame: 4/1/2018 - 3/31/2023
After the participant is enrolled, they will receive several neurocognitive assessments that will be sent digitally, including the Behavioral Rating Inventory of Executive Function (BRIEF).The BRIEF assesses impairment of executive function by evaluating eight clinical scales of executive function including inhibit, shift, emotional control, initiate, working memory, plan/organize, organization of materials, and monitor.The BRIEF exists for preschool children (2-5) and there are self-report versions for adolescents and adults.
Assessment of adaptive function in patients with LBSL using standardized neurocognitive surveys.
Time frame: 4/1/2018 - 3/31/2023
After the participant is enrolled, they will receive several neurocognitive assessments that will be sent digitally, including the Adaptive Behavior Assessment System version 3 (ABAS-3). The ABAS-3 survey assesses eleven essential skill areas in 3 major adaptive domains including conceptual, social and practical, and assists in diagnosing various developmental, learning, and behavioral disabilities. This complete battery of adaptive skills can be administered across the life span for ages Birth-89 years.
Assessment of quality of life in patients with LBSL using standardized surveys.
Time frame: 4/1/2018 - 3/31/2023
After the participant is enrolled, they will receive several quality of life assessments that will be sent digitally. Information on quality of life in LBSL will be collected using well-validated scales addressing physical, emotional, social and school functioning. Relevant scales include quality of life in children and adults with spasticity, quality of life in children and adults with ataxia, and quality of life in children and adults with chronic medical conditions.
Assessment of ataxia in patients with LBSL using wearable sensor technology and standardized clinical scales.
Time frame: 4/1/2018 - 3/31/2023
The study team will collect information about ataxia using wearable sensors and by administering the Standardized Assessment and Rating of Ataxia (SARA) scale at participant's homes. The SARA scale is an 8-item performance based scale that assesses upper and lower extremity ataxia. A total score of 0 indicates no ataxia and the maximum score of 40 indicates severe ataxia.
Assessment of balance in patients with LBSL using wearable sensor technology.
Time frame: 4/1/2018 - 3/31/2023
The study team will collect information about gait and balance ability over time using functional surveys as well as wearable sensors to be used at the participant's homes. This series of tests will require the participant to stand in several different poses for 2 trials of 30 seconds each to assess their balance. This will include standing with their eyes open and their feet apart and together, as well as with their eyes closed and their feet apart and together.
Timed Up and Go Test
Time frame: 4/1/2018 - 3/31/2023
This test will require the participant to sit in a chair. When the participant is instructed to, they will stand up from the chair, walk 3 meters in a straight line, turn around and walk back to the chair. The test duration and variables such as walking and turning speed will be obtained.
Long Walk Test
Time frame: 4/1/2018 - 3/31/2023
This test will require the participant to walk 22 feet in a straight line for a duration of 2 minutes. Variables such as walking and turning speed, stride length and step-to-step variability will be obtained.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Jul 2024.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Amena S Fine, MD PhD principal investigator
Moser Center for Leukodystrophies at Kennedy Krieger Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Leukoencephalopathies and LBSL, run by Hugo W. Moser Research Institute at Kennedy Krieger, Inc. at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 3 Jul 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Aditii Makwana, MS (667-205-4498 ext. 4498, makwana@kennedykrieger.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Track Natural History of LBSL patients using medical record review (time frame: 4/1/2018 - 3/31/2023). The study lists 10 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Jul 2024.