Genetic Investigations in Children With Developmental and Epileptic Encephalopathies in Ho Chi Minh City, Vietnam

NCT05722990 | Recruiting DMC

• 1 other identifier: DEE
• Study Type: observational
• Target: 150
• Locations: 1 country
• Sites: 1

Brief Summary

Early childhood is one of the periods of life in which the risk to develop epilepsy is highest. Besides, genetic causes are much more common in the young. Recently, an ever-increasing amount of genes has been found to be involved in numerous early-onset epilepsies. Thanks to next-generation sequencing (NGS), a diagnosis can now be reached in close to 50% of children with epilepsy and developmental delay. This, in turn, has led to the successful application of the concept of individualized treatment in a growing number of children with epilepsy. Genetic investigations have thus been progressively included in the routine work-up of children with early-onset epilepsies throughout the world, mostly in high-income countries up to now. As a result of a scientific collaboration between pediatric neurology divisions at University Hospitals Geneva (HUG), Switzerland, and Children's Hospital 2 in Ho Chi Minh City (HCMC), Viet Nam, genetic testing of children with early-onset epilepsies followed at the pediatric neurology division, Children's Hospital 2 started at the genetics laboratory of the Vietnam National University in 2017. Aims: Our project aims at establishing the proportion of patients in whom a causal genetic finding can be identified, in a prospective cohort of children with Developmental and Epileptic Encephalopathies (DEE) followed at Children's Hospital 2 (ND2). The investigators also aim at identifying the percentage of these children in whom this approach would change current management. Methods: A series of children diagnosed with DEE and followed at ND2 Hospital, enrolled consecutively. Exome sequencing was applied to all, with biostatistical analyses of a panel of 671 genes involved in epilepsies and developmental disorders performed in parallel at Ho Chi Minh City Vietnam National University and Geneva Genetic Medicine Division. Sanger sequencing confirmation of potentially causal variants in patients, and in parents for familial segregation. Comparison of Vietnamese and Swiss genetic findings, and multidisciplinary discussions in formal Genome Boards. Additional genetic investigations, if deemed necessary in Genome Board sessions. Clinical management adapted to genetic findings wherever applicable, and follow-up according to standard practice. One-hundred-and-fifty patients are expected to participate during the 3-year study period.

Conditions

Whole Exome Sequencing; Epileptic Encephalopathy

Outcome Measures

Primary Outcomes (2)

• The proportion of children with developmental and epileptic encephalopathies for whom advanced genetic investigations allow the identification of pathogenic gene variants

  the proportion of children with developmental and epileptic encephalopathies followed at the largest paediatric neurology facility in South Vietnam and enrolled consecutively for whom advanced genetic investigations allow the identification of pathogenic gene variants.

  36 months

• The proportion of children in whom the genetic results will allow individualized treatment adaptations

  proportion of children in whom the genetic results will allow individualized treatment adaptations

  36 months

Eligibility Criteria

• Age: 1 Day - 3 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)
• Sampling Method: Probability Sample

Study Population

Based on a birth rate of 16.745 children/1000 people in Vietnam (VN), a mortality rate of 15.9/1'000 live births in VN, a total of 1'394'401 live births in VN, and a nationwide population of 97'752'966 which 8'602'317 live in Ho Chi Minh City (HCMC), we estimate that 122'708 to 144'046 children are born in the city each year, of which 120'756 to 141'756 will stay alive. On the basis of a recently calculated general incidence of 54/100'000 live births in Australia, and a comparable age-adjusted incidence of 44.8/100'000 persons in Ba Vi, a rural district of VN, we estimate that 54-75 children with DEE are born every year in HCMC. Given the fact that a majority of these children are followed at Nhi Dong 2 hospital, our aim is to enroll 50 children per year.

You may qualify if:

• Drug-resistant epilepsy, either from onset, or at follow-up, according to ILAE 2010 criteria
• Severe developmental delay or regression, according to paediatric neurologist evaluation (or developmental quotient \<50, if formally assessed)
• Age of onset of principal symptoms (Seizures, Developmental delay): 0-36 months
• Agreement to take part in the study and signed consent form

You may not qualify if:

• Patients with identified structural, infectious or inflammatory causes (such as perinatal hypoxic-ischemic encephalopathy, Cerebrovascular disorders, Sequelae of trauma or encephalitis, neurocutaneous disorders, etc…) will not be asked to take part to the study.

Sponsors & Collaborators

• Number 2 Children's Hospital, Ho Chi Minh City: lead
• Swiss National Science Foundation: collaborator
• School of Medicine - Vietnam National University at Ho Chi Minh city: collaborator
• University of Medicine and Pharmacy at Ho Chi Minh City: collaborator
• University Hospital, Geneva: collaborator

Study Sites (1)

N02 Children's Hospital

Ho Chi Minh City, Ho Chi Minh, 848, Vietnam

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

For each participant and both his/her parents, 2-5 ml of whole blood will be sampled and stored in tubes coated with K2/K3-Ethylenediaminetetraacetic acid (EDTA) anticoagulants. Genomic DNA will be extracted using a DNA Mini Blood Isolation kit (QIAGEN DmbH, Netherlands). DNA quantity will be measured by Quant-iTTM PicoGreenTM dsDNA Assay Kit (Invitrogen), an ultra-sensitive fluorescent nucleic acid stain method for quantitating double-stranded DNA, using Victor 3 fluorometry, and the condition of DNA will be assessed by 1% gel electrophoresis to ensure the quality and quantity of DNA samples before the sequencing step.

Study Officials

• Thuy-Minh-Thu NGUYEN, MD

  http://www.benhviennhi.org.vn/

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Thuy-Minh-Thu NGUYEN, MD

CONTACT

+84983966371; thunguyen@ump.edu.vn

Hoang-Bao-Trang PHAM, MD

CONTACT

+8490903618; trangbaopham.pnt@gmail.com

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: PROSPECTIVE
• Target Duration: 36 Months
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: February 1, 2023
• First Posted: February 10, 2023
• Study Start: March 16, 2022
• Primary Completion: March 16, 2025
• Study Completion: December 31, 2025
• Last Updated: February 21, 2024

Record last verified: 2024-02

Locations

VN (1)