Clinical trial NCT06144957: SLC13A5 Deficiency Natural History Study - United States Only
Official title: SLC13A5 Deficiency: a Prospective Natural History Study - United States Only
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Citrate Transporter Deficiency
Epilepsy
Rare Diseases
Movement Disorders
Genetic Disorder
SLC13A5 Deficiency
EIEE25
Kohlschutter-Tonz Syndrome (non-ROGDI)
Citrate Transporter Disorder
DEE25
Keywords: Epilepsy
Rare Disease
Movement Disorders
Genetic Disorder
Citrate Transporter Disorder
SLC13A5 Deficiency
EIEE25
Neonatal seizures
autosomal recessive
DEE25
Lead sponsor: TESS Research Foundation
Sponsor class: OTHER
Collaborators: name: Stanford University
name: Brown University
name: University of Texas Southwestern Medical Center
First posted: 2023-11-22
Enrollment: 17
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Study population will consist of children, adolescents, and adults with suspected or confirmed diagnosis of SLC13A5 Deficiency and consistent clinical characteristics.

Brief summary: SLC13A5 deficiency (Citrate Transporter Disorder, EIEE 25) is a rare genetic disorder with neurodevelopmental delays and seizure onset in the first few days of life. This natural history study is designed to address the lack of understanding of disease progression. Additionally it will identify clinical and biomarker endpoints for use in future clinical trials.

Detailed description: This is a longitudinal observational study of the natural history of SLC13A5 deficiency for up to 2 years. This study does not involve any therapeutic intervention. The study includes in-person clinical assessments and laboratory analyses including standardized clinical evaluations, neurocognitive and quality of life scales, video movement rating scale, laboratory measurements of blood and urine, EEG capturing wake and sleep, EKG. Additionally, remote assessments in 1st year (every 3 months) and 2nd year (every 4 months) of enrollment will be made and caregiver will be asked to keep a seizure diary for the duration of the study. Personnel having expertise to comprehensively evaluate biological pathways that are perturbed by SLC13A5 deficiency will analyze the collected data. Improved understanding of disease pathogenesis will guide therapeutics and reveal clinical and biomarker endpoints for use in future clinical trials.

Eligibility criteria: Inclusion Criteria:

1. Parent(s)/legal representative and/or patient must be willing and able to give informed consent/assent for participation in the study.
2. Males and females of any age are eligible for this study
3. Suspected or confirmed diagnosis of SLC135 deficiency with genetic variants in both SLC13A5 alleles and consistent clinical characteristics. Variants of uncertain significance in one or both alleles are acceptable if deemed good candidates by participant's primary geneticist or neurologist and study personnel.
4. Participant and caregiver must be willing to provide clinical data, participate in standardized assessments, and provide biological samples.
5. Willingness to travel to one of the three sites annually is favored, but not required.

Exclusion Criteria:

1. The presence of a second, confirmed disorder, genetic or otherwise, affecting neurodevelopment or with other overlapping symptoms of SLC13A5 deficiency.

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Primary outcomes:
measure: Detailed phenotyping of the clinical course of SLC13A5 deficiency over time: general evaluations
timeFrame: Up to 24 months
measure: Detailed phenotyping of the clinical course of SLC13A5 deficiency over time: vitals and biometrics evaluations
timeFrame: Up to 24 months
measure: Detailed phenotyping of the clinical course of SLC13A5 deficiency over time: neurologic evaluation
timeFrame: Up to 24 months
measure: Detailed phenotyping of the clinical course of SLC13A5 deficiency over time: dental evaluations
timeFrame: Up to 24 months
measure: Detailed phenotyping of the clinical course of SLC13A5 deficiency over time: clinical and research laboratory studies
timeFrame: Up to 24 months
measure: Detailed phenotyping of the clinical course of SLC13A5 deficiency over time: electroencephalogram (EEG)
timeFrame: Up to 24 months
measure: Detailed phenotyping of the clinical course of SLC13A5 deficiency over time: scoring of movement disorder and SLC13A5 deficiency symptom scales
timeFrame: Up to 24 months
measure: Neurodevelopmental profile of SLC13A5 deficiency as measured using Mullen Scales of Early Learning
timeFrame: Up to 24 months
measure: Neurodevelopmental profile of SLC13A5 deficiency as measured using the Peabody Developmental Motor Scales-2
timeFrame: Up to 24 months
measure: Neurodevelopmental profile of SLC13A5 deficiency as measured using the Vineland-III Adaptive Behavior Scale
timeFrame: Up to 24 months
measure: Seizure burden and semiology as measured using the Seizure Global Impression of Change
timeFrame: Up to 24 months
Secondary outcomes:
measure: Participant quality of life as measured through the Pediatric Quality of Life Inventory (PedsQL) Family Impact
timeFrame: Up to 24 months
measure: Participant quality of life as measured through the Pediatric Quality of Life Inventory (PedsQL) Caregiver Epilepsy Module
timeFrame: Up to 24 months
measure: Participant sleep disturbances as measured through the Sleep Disturbances Scale for Children (SDSC)
timeFrame: Up to 24 months
Other outcomes:
Locations:
city: Palo Alto
country: United States
facility: Lucille Packard Children's Hospital, Stanford University
state: California
city: Providence
country: United States
facility: Brown University
state: Rhode Island
city: Dallas
country: United States
facility: University of Texas Southwestern Dallas
state: Texas
Study officials:
affiliation: Stanford University
name: Brenda E Porter, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Texas Southwestern Dallas
name: Kimberly Goodspeed, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Brown University
name: Judy Liu, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
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