SLC13A5 Deficiency Natural History Study - United States Only

Официальное название

SLC13A5 Deficiency: A Prospective Natural History Study - United States Only

Обзор

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.

Подробное описание

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.

Первичные конечные точки

• Detailed phenotyping of the clinical course of SLC13A5 deficiency over time: general evaluations [Срок оценки: Up to 24 months]
• Detailed phenotyping of the clinical course of SLC13A5 deficiency over time: vitals and biometrics evaluations [Срок оценки: Up to 24 months]
• Detailed phenotyping of the clinical course of SLC13A5 deficiency over time: neurologic evaluation [Срок оценки: Up to 24 months]
• Detailed phenotyping of the clinical course of SLC13A5 deficiency over time: dental evaluations [Срок оценки: Up to 24 months]
• Detailed phenotyping of the clinical course of SLC13A5 deficiency over time: clinical and research laboratory studies [Срок оценки: Up to 24 months]
• Detailed phenotyping of the clinical course of SLC13A5 deficiency over time: electroencephalogram (EEG) [Срок оценки: Up to 24 months]
• Detailed phenotyping of the clinical course of SLC13A5 deficiency over time: scoring of movement disorder and SLC13A5 deficiency symptom scales [Срок оценки: Up to 24 months]
• Neurodevelopmental profile of SLC13A5 deficiency as measured using Mullen Scales of Early Learning [Срок оценки: Up to 24 months]
• Neurodevelopmental profile of SLC13A5 deficiency as measured using the Peabody Developmental Motor Scales-2 [Срок оценки: Up to 24 months]
• Neurodevelopmental profile of SLC13A5 deficiency as measured using the Vineland-III Adaptive Behavior Scale [Срок оценки: Up to 24 months]

Вторичные конечные точки (3)

• Participant quality of life as measured through the Pediatric Quality of Life Inventory (PedsQL) Family Impact [Срок оценки: Up to 24 months]
• Participant quality of life as measured through the Pediatric Quality of Life Inventory (PedsQL) Caregiver Epilepsy Module [Срок оценки: Up to 24 months]
• Participant sleep disturbances as measured through the Sleep Disturbances Scale for Children (SDSC) [Срок оценки: Up to 24 months]

Критерии участия

Критерии включения

• 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.

Критерии исключения

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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Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Модель наблюдения

Только случаи

Центры проведения

США · 3 центра

• Lucille Packard Children's Hospital, Stanford University — Palo Alto
• Brown University — Providence
• University of Texas Southwestern Dallas — Dallas

Публикации

• 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-rece PMID 24995870
• Hardies 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 r PMID 26384929
• Klotz 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. PMID 27261973
• Selch 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. PMID 30054523
• Bainbridge 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. PMID 28673551
• Weeke 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. PMID 27913086
• Irizarry 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. PMID 28406943
• Schossig 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. PMID 27600704

Идентификаторы

NCT: NCT06144957 · SLC13A5USNHS

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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