Clinical trial NCT06054347: Evaluation by a Vineland II Scale of Long-term Development of Children with Pyridoxine Dependent Epilepsy
Official title: Standardized Evaluation of Long-term Neurocognitive Development of Children from Age 3 with Pyridoxine Dependent Epilepsy by Antiquitine Deficiency
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Pyridoxine-Dependent Epilepsy
Lead sponsor: University Hospital, Angers
Sponsor class: OTHER_GOV
First posted: 2023-09-26
Enrollment: 30
Sex: ALL
Minimum age (years): 3
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Cohort of patients diagnosed with pyridoxine dependent epilepsy and already published (Gibaud et al) completed with new cases.

Brief summary: This study aims to evaluate with the VINELAND II scale the long-term neurocognitive development of children above age 3 years with pyridoxine dependent epilepsy related to antiquitine deficiency.

Detailed description: Pyridoxine dependent epilepsy related to antiquitine deficiency is a rare and severe genetic epilepsy that usually starts within the first month of life. The treatment is based on high dose of Vitamin B6 (Pyridoxine) which is usually highly effective to control the seizures. However, most patients show impaired neurodevelopment.

Ten years ago, international recommendations have changed and a lysine restricted diet was added as an adjunct therapy with the hope to improve neurodevelopment.

Very few studies have evaluated the cognitive development of these patients in a standardized way, and these studies evaluate very few patients.

It seems therefore essential to study in a standardized way the neurocognitive development of these patients in order to evaluate the impact of the care.

The VINELAND adaptative behaviour scale II has been chosen because it can evaluate a patient whatever the age or the intellectual abilities through a semi-structured questionnaire completed with the parents, and gives a wide view of the neurocognitive development and everyday life autonomy of the patients.

Eligibility criteria: Inclusion Criteria:

* Age above 3 years old
* Pyridoxine dependent epilepsy genetic diagnosis (mutation in ALDH7A1 gene)
* No objection of the patient or his legal representatives.

Exclusion Criteria:

* Poor understanding of French language.

Primary outcomes:
measure: Vineland II Adaptive Behaviour scales (VABS) total mean score and subscale mean scores
timeFrame: Baseline
Secondary outcomes:
measure: Determine if the treatments actually used for patients with pyridoxine dependent epilepsy have an impact on their long-term neurocognitive development, especially the lysine restricted diet
timeFrame: Baseline
measure: Evaluation of executive functions with the BRIEF scale
timeFrame: Baseline
measure: Clinical and para-clinical description of the population studied
timeFrame: Baseline
measure: genotype phenotype correlation
timeFrame: baseline
Other outcomes:
Locations:
city: Angers
country: France
facility: CHU Angers
city: Besançon
country: France
facility: Centre Hospitalier Universitaire de Besançon
city: Brest
country: France
facility: CHRU Morvan
city: Clermont-Ferrand
country: France
facility: CHU d'Estaing
city: Le Kremlin-Bicêtre
country: France
facility: Hôpital Bicêtre
city: Lille
country: France
facility: Hôpital Jeanne de Flandre
city: Marseille
country: France
facility: Hôpital de la Timone-Enfants
city: Montpeliier
country: France
facility: CHU Gui de Chautiac
city: Paris
country: France
facility: Hôpital Necker-Enfants malades
city: Saint-Nazaire
country: France
facility: Centre Hospitalier Saint Nazaire
city: Toulouse
country: France
facility: CHU Toulouse
city: Tours
country: France
facility: Hôpital Clocheville
Study officials:
affiliation: University Hospital, Angers
name: Patrick VAN BOGAERT, PhD - MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Coughlin CR 2nd, Swanson MA, Spector E, Meeks NJL, Kronquist KE, Aslamy M, Wempe MF, van Karnebeek CDM, Gospe SM Jr, Aziz VG, Tsai BP, Gao H, Nagy PL, Hyland K, van Dooren SJM, Salomons GS, Van Hove JLK. The genotypic spectrum of ALDH7A1 mutations resulting in pyridoxine dependent epilepsy: A common epileptic encephalopathy. J Inherit Metab Dis. 2019 Mar;42(2):353-361. doi: 10.1002/jimd.12045. Epub 2019 Feb 22.
citation: Wilson MP, Plecko B, Mills PB, Clayton PT. Disorders affecting vitamin B6 metabolism. J Inherit Metab Dis. 2019 Jul;42(4):629-646. doi: 10.1002/jimd.12060. Epub 2019 Mar 20.
citation: Basura GJ, Hagland SP, Wiltse AM, Gospe SM Jr. Clinical features and the management of pyridoxine-dependent and pyridoxine-responsive seizures: review of 63 North American cases submitted to a patient registry. Eur J Pediatr. 2009 Jun;168(6):697-704. doi: 10.1007/s00431-008-0823-x. Epub 2008 Sep 2.
citation: Baxter P. Epidemiology of pyridoxine dependent and pyridoxine responsive seizures in the UK. Arch Dis Child. 1999 Nov;81(5):431-3. doi: 10.1136/adc.81.5.431.
citation: Coughlin CR 2nd, Tseng LA, Abdenur JE, Ashmore C, Boemer F, Bok LA, Boyer M, Buhas D, Clayton PT, Das A, Dekker H, Evangeliou A, Feillet F, Footitt EJ, Gospe SM Jr, Hartmann H, Kara M, Kristensen E, Lee J, Lilje R, Longo N, Lunsing RJ, Mills P, Papadopoulou MT, Pearl PL, Piazzon F, Plecko B, Saini AG, Santra S, Sjarif DR, Stockler-Ipsiroglu S, Striano P, Van Hove JLK, Verhoeven-Duif NM, Wijburg FA, Zuberi SM, van Karnebeek CDM. Consensus guidelines for the diagnosis and management of pyridoxine-dependent epilepsy due to alpha-aminoadipic semialdehyde dehydrogenase deficiency. J Inherit Metab Dis. 2021 Jan;44(1):178-192. doi: 10.1002/jimd.12332. Epub 2020 Dec 1.
citation: Tourrette C., Evaluer les enfants avec déficiences ou troubles du développement. PARIS : Dunod, 2006
citation: Fombonne E. ; Achard S. ; Tuffreau R. L'évaluation du comportement adaptatif : l'échelle de Vineland. In Handicap et inadaptations. Les Cahiers du CTNERHI, n° 67-68, juil. / déc. 1995. p. 79-90.3
citation: Gioia GA, Isquith PK, Guy SC, Kenworthy L. The Behaviour Rating Inventory of Executive Function. Lutz, FL: Psychological Assessment Resources; 2000.
citation: Gibaud M, Barth M, Lefranc J, Mention K, Villeneuve N, Schiff M, Maurey H, Barthez MA, Caubel I, Chouchane M, Doummar D, Kossorotoff M, Lamblin MD, Roubertie A, Nabbout R, Van Bogaert P. West Syndrome Is an Exceptional Presentation of Pyridoxine- and Pyridoxal Phosphate-Dependent Epilepsy: Data From a French Cohort and Review of the Literature. Front Pediatr. 2021 Mar 5;9:621200. doi: 10.3389/fped.2021.621200. eCollection 2021.