Citrate Transporter DeficiencyNCT06144957
SLC13A5 Deficiency Natural History Study - United States Only
An observational study of Citrate Transporter Deficiency and Epilepsy, run by TESS Research Foundation at 3 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Citrate Transporter Deficiency, Epilepsy, Rare Diseases
- How many people
- 17 participants
- Where
- 3 sitesUnited States
- Study dates
- 1 Dec 2021to 30 Sep 2025
- 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: Study population will consist of children, adolescents, and adults with suspected or confirmed diagnosis of SLC13A5 Deficiency and consistent clinical characteristics.
Who may be able to join
- Parent(s)/legal representative and/or patient must be willing and able to give informed consent/assent for participation in the study.
- Males and females of any age are eligible for this study
- 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.
- Participant and caregiver must be willing to provide clinical data, participate in standardized assessments, and provide biological samples.
- Willingness to travel to one of the three sites annually is favored, but not required.
Who cannot join
- 1. The presence of a second, confirmed disorder, genetic or otherwise, affecting neurodevelopment or with other overlapping symptoms of SLC13A5 deficiency.
- -
Trial locations and contacts
3 sites in 1 country. Contact the study team or a site near you to ask about taking part.
United States3 sites
University of Texas Southwestern Dallas
Dallas, Texas, 75390
Lucille Packard Children's Hospital, Stanford University
Palo Alto, California, 94304
Brown University
Providence, Rhode Island, 02903
About this study
Official title: SLC13A5 Deficiency: A Prospective Natural History Study - United States Only
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.
Read the 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.
- Conditions
- Citrate Transporter Deficiency, Epilepsy, Rare Diseases, Movement Disorders, Genetic Disorder, SLC13A5 Deficiency
- Keywords
- Epilepsy, Rare Disease, Movement Disorders, Genetic Disorder, Citrate Transporter Disorder, SLC13A5 Deficiency, EIEE25, Neonatal seizures, autosomal recessive, DEE25
- Medical subject headings
- Epilepsy, Rare Diseases, Movement Disorders, Genetic Diseases, Inborn, Kohlschutter Tonz syndrome
What is being measured
The primary outcome is the main question the study is designed to answer.
Detailed phenotyping of the clinical course of SLC13A5 deficiency over time: general evaluations
Conducted in patients with SLC13A5 deficiency: general appearance, HEENT, neck, chest and lungs, cardiovascular, abdomen, genitourinary, rectal, musculoskeletal, lymph nodes, extremities/skin, mental status (alertness, interaction, language (EXP) (REC)), emotional affect (calm, smiling, laughing, anxious, frowning, crying, irritable, screaming).
As much information as available will also be collected from existing medical records including clinical evaluations, imaging studies and neuropsychological and motor function evaluations.
Measured: Up to 24 months
Detailed phenotyping of the clinical course of SLC13A5 deficiency over time: vitals and biometrics evaluations
Conducted in patients with SLC13A5 deficiency: height (cm), weight (kg), blood pressure (systolic and diastolic), temperature (c), heart rate (beats/minute), respiratory rate (breaths/minute), and head circumference (cm).
As much information as available will also be collected from existing medical records including clinical evaluations, imaging studies and neuropsychological and motor function evaluations.
Measured: Up to 24 months
Detailed phenotyping of the clinical course of SLC13A5 deficiency over time: neurologic evaluation
Conducted in patients with SLC13A5 deficiency: motor, motor stability, muscle bulk, paresis, sensation, reflexes, coordination, gait, and autonomic.
As much information as available will also be collected from existing medical records including clinical evaluations, imaging studies and neuropsychological and motor function evaluations.
Measured: Up to 24 months
Detailed phenotyping of the clinical course of SLC13A5 deficiency over time: dental evaluations
Conducted in patients with SLC13A5 deficiency: baseline pain assessment from a scale of 0-10 (0 being no pain and 10 being highest pain), temperature pain assessment for cold from a scale of 0-10 (0 being no pain and 10 being highest pain), temperate pain assessment for hot from a scale of 0-10 (0 being no pain and 10 being highest pain), toothpaste use (type and frequency), and Fluoride treatments.
As much information as available will also be collected from existing medical records including clinical evaluations, imaging studies and neuropsychological and motor function evaluations.
Measured: Up to 24 months
Detailed phenotyping of the clinical course of SLC13A5 deficiency over time: clinical and research laboratory studies
Conducted in patients with SLC13A5 deficiency:
Clinical: ammonia, amylase, CKMB, GGT, lactate, lipase, PT/PTT, vitamin d 25-oh, CBC with differential, comprehensive MET panel, lipid panel with calculated LDL, and urine studies (calcium/creatinine ratio, spot ph, spot citrate concentration, citrate/creatinine ratio).
Research: Citrate and metabolomics.
As much information as available will also be collected from existing medical records including clinical evaluations, imaging studies and neuropsychological and motor function evaluations.
Measured: Up to 24 months
Detailed phenotyping of the clinical course of SLC13A5 deficiency over time: electroencephalogram (EEG)
Conducted in patients with SLC13A5 deficiency: looking at the duration of EEG, if they are captured awake or asleep, and if it is abnormal.
As much information as available will also be collected from existing medical records including clinical evaluations, imaging studies and neuropsychological and motor function evaluations.
Measured: Up to 24 months
Detailed phenotyping of the clinical course of SLC13A5 deficiency over time: scoring of movement disorder and SLC13A5 deficiency symptom scales
Conducted in patients with SLC13A5 deficiency: using scale titled "Movement Exam for SLC13A5 Natural History Study". Assessing typical gait, standing in natural position, sitting on chair, head control, attempt to vocalize, speech quality, speech content, ability to grab items, and ability to draw. Symptom scales consist of chorea, dystonia, ataxia, myoclonus, tremor, hypokinetic-rigid syndrome, and tic.
As much information as available will also be collected from existing medical records including clinical evaluations, imaging studies and neuropsychological and motor function evaluations.
Measured: Up to 24 months
Neurodevelopmental profile of SLC13A5 deficiency as measured using Mullen Scales of Early Learning
Consists of a gross-motor scale and four cognitive scales: visual reception, fine motor, receptive language, and expressive language. T-Scores (mean of 50 and a standard deviation of 10) are given for individual scales, and an optional Early Learning Composite standard score (mean of 100 and a standard deviation of 15) serves as an overall estimate of cognitive functioning. This is based on child's age and there are no higher or lower scores that indicate a better or worse outcome.
Developmental assessment at baseline and longitudinally, if age and ability-appropriate.
Measured: Up to 24 months
Neurodevelopmental profile of SLC13A5 deficiency as measured using the Peabody Developmental Motor Scales-2
Six subtests that measure motor ability in children: reflexes, stationary, locomotion, object manipulation, grasping, and visual motor integration. The Peabody has quotients that measure a child's motor ability: gross motor quotient, fine motor quotient, total motor quotient. This is based on child's age and there are no higher or lower scores that indicate a better or worse outcome.
Developmental assessment at baseline and longitudinally, if age and ability-appropriate.
Measured: Up to 24 months
Neurodevelopmental profile of SLC13A5 deficiency as measured using the Vineland-III Adaptive Behavior Scale
Vineland is a semi-structured interview that assesses adaptive behavior in several domains, summarized by the Adaptive Behavior Composite (ABC) standard score. ABC standard scores may range from 20 to 160, with a population mean of 100 and a standard deviation of 15. There are no higher or lower scores that indicate a better or worse outcome.
Developmental assessment at baseline and longitudinally, if age and ability-appropriate. Additionally, Vineland-III Adaptive Behavior Scale questionnaire will be included in the remote assessment interview.
Measured: Up to 24 months
Seizure burden and semiology as measured using the Seizure Global Impression of Change
Assessing the status of the patient's overall condition using a scale ranging from very much improved, much improved, slightly improved, no change, slightly worse, much worse, very much worse. Assessing the average number of participants' seizures on a scale of decreased, stayed the same, increased. Assessing the average duration of the participants' seizures on a scale of decreased, stayed the same, increased.
Caregiver will be asked to maintain a seizure diary throughout the study and seizure burden will be assessed at in-person and remote assessments.
Measured: Up to 24 months
Secondary outcomes (3)
Participant quality of life as measured through the Pediatric Quality of Life Inventory (PedsQL) Family Impact
The PedsQL Family Impact Module measures parent self-reported physical, emotional, social, and cognitive functioning, communication, and worry. The Module also measures parent-reported family daily activities and family relationships.
Items are reverse-scored and linearly transformed to a 0-100 scale (0 = 100, 1 = 75, 2 = 50, 3 = 25, 4 = 0), so that higher scores indicate better functioning (less negative impact). Scale Scores are computed as the sum of the items divided by the number of items answered (this accounts for missing data).
Quality of life will be evaluated at baseline and longitudinally.
Measured: Up to 24 months
Participant quality of life as measured through the Pediatric Quality of Life Inventory (PedsQL) Caregiver Epilepsy Module
The PedsQL Epilepsy Module is a 29-item measure with five scales: Impact, Cognitive, Sleep, Executive Function, and Mood/Behavior.
Items are reverse-scored and linearly transformed to a 0-100 scale (0 = 100, 1 = 75, 2 = 50, 3 = 25, 4 = 0), so that higher scores indicate better functioning (less negative impact). Scale Scores are computed as the sum of the items divided by the number of items answered (this accounts for missing data).
Quality of life will be evaluated at baseline and longitudinally.
Measured: Up to 24 months
Participant sleep disturbances as measured through the Sleep Disturbances Scale for Children (SDSC)
Consisting of 26 Likert-type items, the SDSC was designed both to evaluate specific sleep disorders in children, and to provide an overall measure of sleep disturbance suitable for use in clinical screening and research.
Higher scores indicate more acute sleep disturbances. To obtain results, scores are tallied for each of the six sleep-disorder categories, and an overall score is calculated.
The sleep disturbances will be evaluated at baseline and longitudinally.
Measured: Up to 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Nov 2023
- Study start1 Dec 2021
- Primary completion30 Sep 2025 (estimated)
- Study completion30 Sep 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (8)Papers the sponsor has linked to this study.
- Other trials for Citrate Transporter DeficiencyStudies 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
- Case only
- Time perspective
- Prospective
- Enrolment
- 17 participants (estimated)
Sponsor and investigators
- Lead sponsor
- TESS Research Foundation
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Brenda E Porter, MD, PhD, Principal investigator, Stanford UniversityKimberly Goodspeed, MD, PhD, Principal investigator, University of Texas Southwestern DallasJudy Liu, MD, PhD, Principal investigator, Brown University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06144957
- Sponsor's protocol ID
- SLC13A5USNHS
- Status last verified
- Nov 2024
- First submitted
- 7 Jan 2022
- Last updated
- 5 Aug 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: The study data will be retained in the study-specific REDCap data base housed at redcap.stanford.edu. Researchers and clinicians with academic interest in SLC13A5 deficiency may be provided access to data obtained through this study. Any data shared outside of Stanford University will be done so in a coded fashion with no protected health information included and with the execution of all applicable agreements or ongoing collaborations as approved.
Publications
Thevenon J, Milh M, Feillet F, St-Onge J, Duffourd Y, Juge C, Roubertie A, Heron D, Mignot C, Raffo E, Isidor B, Wahlen S, Sanlaville D, Villeneuve N, Darmency-Stamboul V, Toutain A, Lefebvre M, Chouchane M, Huet F, Lafon A, de Saint Martin A, Lesca G, El Chehadeh S, Thauvin-Robinet C, Masurel-Paulet A, Odent S, Villard L, Philippe C, Faivre L, Riviere JB. Mutations in SLC13A5 cause autosomal-recessive epileptic encephalopathy with seizure onset in the first days of life. Am J Hum Genet. 2014 Jul 3;95(1):113-20. doi: 10.1016/j.ajhg.2014.06.006.
PubMed 24995870Hardies K, de Kovel CG, Weckhuysen S, Asselbergh B, Geuens T, Deconinck T, Azmi A, May P, Brilstra E, Becker F, Barisic N, Craiu D, Braun KP, Lal D, Thiele H, Schubert J, Weber Y, van 't Slot R, Nurnberg P, Balling R, Timmerman V, Lerche H, Maudsley S, Helbig I, Suls A, Koeleman BP, De Jonghe P; autosomal recessive working group of the EuroEPINOMICS RES Consortium. Recessive mutations in SLC13A5 result in a loss of citrate transport and cause neonatal epilepsy, developmental delay and teeth hypoplasia. Brain. 2015 Nov;138(Pt 11):3238-50. doi: 10.1093/brain/awv263. Epub 2015 Sep 17.
PubMed 26384929Klotz J, Porter BE, Colas C, Schlessinger A, Pajor AM. Mutations in the Na(+)/citrate cotransporter NaCT (SLC13A5) in pediatric patients with epilepsy and developmental delay. Mol Med. 2016 May 26;22:310-21. doi: 10.2119/molmed.2016.00077.
PubMed 27261973Selch S, Chafai A, Sticht H, Birkenfeld AL, Fromm MF, Konig J. Analysis of naturally occurring mutations in the human uptake transporter NaCT important for bone and brain development and energy metabolism. Sci Rep. 2018 Jul 27;8(1):11330. doi: 10.1038/s41598-018-29547-8.
PubMed 30054523Bainbridge MN, Cooney E, Miller M, Kennedy AD, Wulff JE, Donti T, Jhangiani SN, Gibbs RA, Elsea SH, Porter BE, Graham BH. Analyses of SLC13A5-epilepsy patients reveal perturbations of TCA cycle. Mol Genet Metab. 2017 Aug;121(4):314-319. doi: 10.1016/j.ymgme.2017.06.009. Epub 2017 Jun 24.
PubMed 28673551Weeke LC, Brilstra E, Braun KP, Zonneveld-Huijssoon E, Salomons GS, Koeleman BP, van Gassen KL, van Straaten HL, Craiu D, de Vries LS. Punctate white matter lesions in full-term infants with neonatal seizures associated with SLC13A5 mutations. Eur J Paediatr Neurol. 2017 Mar;21(2):396-403. doi: 10.1016/j.ejpn.2016.11.002. Epub 2016 Nov 19.
PubMed 27913086Irizarry AR, Yan G, Zeng Q, Lucchesi J, Hamang MJ, Ma YL, Rong JX. Defective enamel and bone development in sodium-dependent citrate transporter (NaCT) Slc13a5 deficient mice. PLoS One. 2017 Apr 13;12(4):e0175465. doi: 10.1371/journal.pone.0175465. eCollection 2017.
PubMed 28406943Schossig A, Bloch-Zupan A, Lussi A, Wolf NI, Raskin S, Cohen M, Giuliano F, Jurgens J, Krabichler B, Koolen DA, de Macena Sobreira NL, Maurer E, Muller-Bolla M, Penzien J, Zschocke J, Kapferer-Seebacher I. SLC13A5 is the second gene associated with Kohlschutter-Tonz syndrome. J Med Genet. 2017 Jan;54(1):54-62. doi: 10.1136/jmedgenet-2016-103988. Epub 2016 Sep 6.
PubMed 27600704
Study at a glance
From the registry record, last updated by the sponsor on 5 Aug 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- SLC13A5 Deficiency: A Prospective Natural History Study - United States Only
- ClinicalTrials.gov ID
- NCT06144957
- Acronym / sponsor ID
- SLC13A5USNHS
- Conditions
- Citrate Transporter Deficiency, Epilepsy, Rare Diseases, Movement Disorders, Genetic Disorder, SLC13A5 Deficiency
- Keywords
- Epilepsy, Rare Disease, Movement Disorders, Genetic Disorder, Citrate Transporter Disorder, SLC13A5 Deficiency, EIEE25, Neonatal seizures
- Study type
- Observational
- Recruitment status
- Enrolling by invitation
- Enrolment
- 17 participants (estimated)
- Lead sponsor
- TESS Research FoundationUniversity, hospital or other
- Collaborators
- Stanford University, Brown University, University of Texas Southwestern Medical Center
- Study start
- 1 Dec 2021 (actual)
- Primary completion
- 30 Sep 2025 (estimated)
- Study completion
- 30 Sep 2025 (estimated)
- First posted
- 22 Nov 2023 (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.
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.
Study design
- Observational model
- Case only
- Time perspective
- Prospective
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Study population will consist of children, adolescents, and adults with suspected or confirmed diagnosis of SLC13A5 Deficiency and consistent clinical characteristics.
Key inclusion criteria (5 listed)
- Parent(s)/legal representative and/or patient must be willing and able to give informed consent/assent for participation in the study.
- Males and females of any age are eligible for this study
- 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.
- Participant and caregiver must be willing to provide clinical data, participate in standardized assessments, and provide biological samples.
- Willingness to travel to one of the three sites annually is favored, but not required.
Key exclusion criteria (2 listed)
- 1. The presence of a second, confirmed disorder, genetic or otherwise, affecting neurodevelopment or with other overlapping symptoms of SLC13A5 deficiency.
- -
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
Detailed phenotyping of the clinical course of SLC13A5 deficiency over time: general evaluations
Time frame: Up to 24 months
Conducted in patients with SLC13A5 deficiency: general appearance, HEENT, neck, chest and lungs, cardiovascular, abdomen, genitourinary, rectal, musculoskeletal, lymph nodes, extremities/skin, mental status (alertness, interaction, language (EXP) (REC)), emotional affect (calm, smiling, laughing, anxious, frowning, crying, irritable, screaming). As much information as available will also be collected from existing medical records including clinical evaluations, imaging studies and neuropsychological and motor function evaluations.
Detailed phenotyping of the clinical course of SLC13A5 deficiency over time: vitals and biometrics evaluations
Time frame: Up to 24 months
Conducted in patients with SLC13A5 deficiency: height (cm), weight (kg), blood pressure (systolic and diastolic), temperature (c), heart rate (beats/minute), respiratory rate (breaths/minute), and head circumference (cm). As much information as available will also be collected from existing medical records including clinical evaluations, imaging studies and neuropsychological and motor function evaluations.
Detailed phenotyping of the clinical course of SLC13A5 deficiency over time: neurologic evaluation
Time frame: Up to 24 months
Conducted in patients with SLC13A5 deficiency: motor, motor stability, muscle bulk, paresis, sensation, reflexes, coordination, gait, and autonomic. As much information as available will also be collected from existing medical records including clinical evaluations, imaging studies and neuropsychological and motor function evaluations.
Detailed phenotyping of the clinical course of SLC13A5 deficiency over time: dental evaluations
Time frame: Up to 24 months
Conducted in patients with SLC13A5 deficiency: baseline pain assessment from a scale of 0-10 (0 being no pain and 10 being highest pain), temperature pain assessment for cold from a scale of 0-10 (0 being no pain and 10 being highest pain), temperate pain assessment for hot from a scale of 0-10 (0 being no pain and 10 being highest pain), toothpaste use (type and frequency), and Fluoride treatments. As much information as available will also be collected from existing medical records including clinical evaluations, imaging studies and neuropsychological and motor function evaluations.
Detailed phenotyping of the clinical course of SLC13A5 deficiency over time: clinical and research laboratory studies
Time frame: Up to 24 months
Conducted in patients with SLC13A5 deficiency: Clinical: ammonia, amylase, CKMB, GGT, lactate, lipase, PT/PTT, vitamin d 25-oh, CBC with differential, comprehensive MET panel, lipid panel with calculated LDL, and urine studies (calcium/creatinine ratio, spot ph, spot citrate concentration, citrate/creatinine ratio). Research: Citrate and metabolomics. As much information as available will also be collected from existing medical records including clinical evaluations, imaging studies and neuropsychological and motor function evaluations.
Detailed phenotyping of the clinical course of SLC13A5 deficiency over time: electroencephalogram (EEG)
Time frame: Up to 24 months
Conducted in patients with SLC13A5 deficiency: looking at the duration of EEG, if they are captured awake or asleep, and if it is abnormal. As much information as available will also be collected from existing medical records including clinical evaluations, imaging studies and neuropsychological and motor function evaluations.
Detailed phenotyping of the clinical course of SLC13A5 deficiency over time: scoring of movement disorder and SLC13A5 deficiency symptom scales
Time frame: Up to 24 months
Conducted in patients with SLC13A5 deficiency: using scale titled "Movement Exam for SLC13A5 Natural History Study". Assessing typical gait, standing in natural position, sitting on chair, head control, attempt to vocalize, speech quality, speech content, ability to grab items, and ability to draw. Symptom scales consist of chorea, dystonia, ataxia, myoclonus, tremor, hypokinetic-rigid syndrome, and tic. As much information as available will also be collected from existing medical records including clinical evaluations, imaging studies and neuropsychological and motor function evaluations.
Neurodevelopmental profile of SLC13A5 deficiency as measured using Mullen Scales of Early Learning
Time frame: Up to 24 months
Consists of a gross-motor scale and four cognitive scales: visual reception, fine motor, receptive language, and expressive language. T-Scores (mean of 50 and a standard deviation of 10) are given for individual scales, and an optional Early Learning Composite standard score (mean of 100 and a standard deviation of 15) serves as an overall estimate of cognitive functioning. This is based on child's age and there are no higher or lower scores that indicate a better or worse outcome. Developmental assessment at baseline and longitudinally, if age and ability-appropriate.
Neurodevelopmental profile of SLC13A5 deficiency as measured using the Peabody Developmental Motor Scales-2
Time frame: Up to 24 months
Six subtests that measure motor ability in children: reflexes, stationary, locomotion, object manipulation, grasping, and visual motor integration. The Peabody has quotients that measure a child's motor ability: gross motor quotient, fine motor quotient, total motor quotient. This is based on child's age and there are no higher or lower scores that indicate a better or worse outcome. Developmental assessment at baseline and longitudinally, if age and ability-appropriate.
Neurodevelopmental profile of SLC13A5 deficiency as measured using the Vineland-III Adaptive Behavior Scale
Time frame: Up to 24 months
Vineland is a semi-structured interview that assesses adaptive behavior in several domains, summarized by the Adaptive Behavior Composite (ABC) standard score. ABC standard scores may range from 20 to 160, with a population mean of 100 and a standard deviation of 15. There are no higher or lower scores that indicate a better or worse outcome. Developmental assessment at baseline and longitudinally, if age and ability-appropriate. Additionally, Vineland-III Adaptive Behavior Scale questionnaire will be included in the remote assessment interview.
Seizure burden and semiology as measured using the Seizure Global Impression of Change
Time frame: Up to 24 months
Assessing the status of the patient's overall condition using a scale ranging from very much improved, much improved, slightly improved, no change, slightly worse, much worse, very much worse. Assessing the average number of participants' seizures on a scale of decreased, stayed the same, increased. Assessing the average duration of the participants' seizures on a scale of decreased, stayed the same, increased. Caregiver will be asked to maintain a seizure diary throughout the study and seizure burden will be assessed at in-person and remote assessments.
3 secondary outcomes
Participant quality of life as measured through the Pediatric Quality of Life Inventory (PedsQL) Family Impact
Time frame: Up to 24 months
Participant quality of life as measured through the Pediatric Quality of Life Inventory (PedsQL) Caregiver Epilepsy Module
Time frame: Up to 24 months
Participant sleep disturbances as measured through the Sleep Disturbances Scale for Children (SDSC)
Time frame: Up to 24 months
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 5 Aug 2025.
- Background: PubMed 24995870Thevenon J, Milh M, Feillet F, St-Onge J, Duffourd Y, Juge C, Roubertie A, Heron D, Mignot C, Raffo E, Isidor B, Wahlen S, Sanlaville D, Villeneuve N, Darmency-Stamboul V, Toutain A, Lefebvre M, Chouchane M, Huet F, Lafon A, de Saint Martin A, Lesca G, El Chehadeh S, Thauvin-Robinet C, Masurel-Paulet A, Odent S, Villard L, Philippe C, Faivre L, Riviere JB. Mutations in SLC13A5 cause autosomal-recessive epileptic encephalopathy with seizure onset in the first days of life. Am J Hum Genet. 2014 Jul 3;95(1):113-20. doi: 10.1016/j.ajhg.2014.06.006.
- Background: PubMed 26384929Hardies K, de Kovel CG, Weckhuysen S, Asselbergh B, Geuens T, Deconinck T, Azmi A, May P, Brilstra E, Becker F, Barisic N, Craiu D, Braun KP, Lal D, Thiele H, Schubert J, Weber Y, van 't Slot R, Nurnberg P, Balling R, Timmerman V, Lerche H, Maudsley S, Helbig I, Suls A, Koeleman BP, De Jonghe P; autosomal recessive working group of the EuroEPINOMICS RES Consortium. Recessive mutations in SLC13A5 result in a loss of citrate transport and cause neonatal epilepsy, developmental delay and teeth hypoplasia. Brain. 2015 Nov;138(Pt 11):3238-50. doi: 10.1093/brain/awv263. Epub 2015 Sep 17.
- Background: PubMed 27261973Klotz J, Porter BE, Colas C, Schlessinger A, Pajor AM. Mutations in the Na(+)/citrate cotransporter NaCT (SLC13A5) in pediatric patients with epilepsy and developmental delay. Mol Med. 2016 May 26;22:310-21. doi: 10.2119/molmed.2016.00077.
- Background: PubMed 30054523Selch S, Chafai A, Sticht H, Birkenfeld AL, Fromm MF, Konig J. Analysis of naturally occurring mutations in the human uptake transporter NaCT important for bone and brain development and energy metabolism. Sci Rep. 2018 Jul 27;8(1):11330. doi: 10.1038/s41598-018-29547-8.
- Background: PubMed 28673551Bainbridge MN, Cooney E, Miller M, Kennedy AD, Wulff JE, Donti T, Jhangiani SN, Gibbs RA, Elsea SH, Porter BE, Graham BH. Analyses of SLC13A5-epilepsy patients reveal perturbations of TCA cycle. Mol Genet Metab. 2017 Aug;121(4):314-319. doi: 10.1016/j.ymgme.2017.06.009. Epub 2017 Jun 24.
- Background: PubMed 27913086Weeke LC, Brilstra E, Braun KP, Zonneveld-Huijssoon E, Salomons GS, Koeleman BP, van Gassen KL, van Straaten HL, Craiu D, de Vries LS. Punctate white matter lesions in full-term infants with neonatal seizures associated with SLC13A5 mutations. Eur J Paediatr Neurol. 2017 Mar;21(2):396-403. doi: 10.1016/j.ejpn.2016.11.002. Epub 2016 Nov 19.
- Background: PubMed 28406943Irizarry AR, Yan G, Zeng Q, Lucchesi J, Hamang MJ, Ma YL, Rong JX. Defective enamel and bone development in sodium-dependent citrate transporter (NaCT) Slc13a5 deficient mice. PLoS One. 2017 Apr 13;12(4):e0175465. doi: 10.1371/journal.pone.0175465. eCollection 2017.
- Background: PubMed 27600704Schossig A, Bloch-Zupan A, Lussi A, Wolf NI, Raskin S, Cohen M, Giuliano F, Jurgens J, Krabichler B, Koolen DA, de Macena Sobreira NL, Maurer E, Muller-Bolla M, Penzien J, Zschocke J, Kapferer-Seebacher I. SLC13A5 is the second gene associated with Kohlschutter-Tonz syndrome. J Med Genet. 2017 Jan;54(1):54-62. doi: 10.1136/jmedgenet-2016-103988. Epub 2016 Sep 6.
- Individual participant dataSharing planned: Yes. The study data will be retained in the study-specific REDCap data base housed at redcap.stanford.edu. Researchers and clinicians with academic interest in SLC13A5 deficiency may be provided access to data obtained through this study. Any data shared outside of Stanford University will be done so in a coded fashion with no protected health information included and with the execution of all applicable agreements or ongoing collaborations as approved.
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Citrate Transporter Deficiency, Epilepsy
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.
Brenda E Porter, MD, PhD principal investigator
Stanford University
Kimberly Goodspeed, MD, PhD principal investigator
University of Texas Southwestern Dallas
Judy Liu, MD, PhD principal investigator
Brown University
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Citrate Transporter Deficiency and Epilepsy, run by TESS Research Foundation at 3 sites 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 5 inclusion and 2 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: enrolling by invitation, as of the sponsor's last update on 5 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites 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?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Detailed phenotyping of the clinical course of SLC13A5 deficiency over time: general evaluations (time frame: Up to 24 months). The study lists 11 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06144957, which also lists 8 linked publications.
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 5 Aug 2025.