Clinical trial NCT05858268: NeuralNET Cerebral Palsy Pilot Study
Official title: The NeuralNET: Research to Impact Diagnosis, Mechanistic Understanding and Treatment of Children's Brain and Mental Health Disorders - A Pilot Study in Cerebral Palsy
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Cerebral Palsy
Lead sponsor: University of Cambridge
Sponsor class: OTHER
Collaborators: name: Rosetrees Trust
name: Isaac Newton Trust
name: NIHR Cambridge Biomedical Research Centre
name: Illumina, Inc.
First posted: 2023-05-15
Enrollment: 66
Sex: ALL
Maximum age (years): 15
Standard ages: CHILD
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Children with a clinical diagnosis of cerebral palsy

Brief summary: The NeuralNET Cerebral Palsy Pilot Study is testing a genetic testing pathway in the NHS for children with cerebral palsy (CP). Other studies suggest that almost one in three peoples' CP is caused by a change in their genes, but more studies are needed to confirm this. A genetic test called whole genome sequencing (WGS) will be used for children who have CP to look for rare changes in genes that cause the condition, and the results of the test will be given to children's doctors within 12 weeks. Knowing that CP has a genetic cause could lead to changes being made to a child's care or treatment that could improve their condition.

The study will test 66 children with CP from 3 hospitals, and also their biological parent(s), if they're available. Following informed consent, the investigators will collect a blood sample from everyone taking part which will be sent for WGS. It is important to understand what families think and feel about the testing. The investigators will ask parents/guardians of the children taking part to fill in two questionnaires, one before and one after WGS. Some parents/guardians will also be interviewed after getting the WGS result, to ask about their experience of the testing. The study will take up to 16 months per family.

The results of this pilot study will tell the investigators if it is feasible for the NHS to use WGS to test children with CP. If so, a larger study testing more children with CP can then be carried out to help decide if this type of WGS-based testing should be made available through the NHS to children with CP whose clinical care might be changed by the result. The genetic findings from this study will also be made available to other researchers and doctors to do more research into CP that might help improve general understanding of the condition and its potential treatment.


Eligibility criteria: Inclusion Criteria:

Children with cerebral palsy (CP):

1. Has a clinical diagnosis of CP in the medical record
2. Any GMFCS score (GMFCS 1-5)
3. Does not have a known genetic diagnosis that explains the CP phenotype
4. Has a parent/legal guardian available who can consent and is willing to complete study questionnaires
5. Invited to participate by a clinician at a participating recruitment site

Biological parents of children with CP will also be included in the study if they are:

1. A biological parent of the child
2. Aged 18 years or above
3. Willing and able to give informed consent for participation in the study Participant type

Exclusion Criteria:

Children with cerebral palsy (CP):

1. Children that have a pre-existing genetic diagnosis from whole genome sequencing or whole-exome sequencing
2. Children not matching the inclusion criteria

Biological parents of children with CP will be excluded from the study if they do not meet the biological parent inclusion criteria i.e. they ARE NOT:

1. A biological parent of the child
2. Aged 18 years or above
3. Willing and able to give informed consent for participation in the study

Primary outcomes:
measure: Feasibility of rapid whole-genome sequencing of children with cerebral palsy
timeFrame: 16 months
Secondary outcomes:
measure: Uptake of WGS testing by families with a child with CP
timeFrame: Baseline
measure: Reasons for declining offer of WGS
timeFrame: 16 months
measure: Identification of specific genetic contributors to CP in the UK
timeFrame: 16 months
measure: Parent/guardian intolerance for uncertainty
timeFrame: baseline
measure: Parent/guardian attitude to genome sequencing
timeFrame: baseline and 16 months
measure: Parent/guardian decisional conflict
timeFrame: baseline
measure: Parent/guardian empowerment
timeFrame: baseline, 16 months
measure: Parent/guardian decisional regret
timeFrame: 16 months
measure: Parent/guardian psychological impact of WGS
timeFrame: 16 months
measure: Impact of WGS on family quality of life
timeFrame: 16 months
measure: Clinical utility of WGS testing in children with CP
timeFrame: 16 months
measure: Number of candidate variants which warrant further investigation of pathogenicity
timeFrame: 16 months
measure: Generation of data to support the refinement of clinical criteria for WGS for CP
timeFrame: 16 months
Other outcomes:
Locations:
city: Cambridge
country: United Kingdom
facility: Cambridge University Hospitals NHS Trust
Study officials:
affiliation: University of Cambridge
name: David Rowitch, MD
role: PRINCIPAL_INVESTIGATOR
References: