Evaluation of sleep in the genetic condition known as SYNGAP1, in children who have SYNGAP1-related intellectual disability

Plain English Summary

Background and study aims
We are investigating how DNA changes (variants) in the SYNGAP1 gene affect sleep. The SYNGAP1 gene provides instructions for making a protein, called SynGAP, that plays an important role in nerve cells in the brain. SynGAP is found at the junctions between nerve cells (synapses) where cell-to-cell communication takes place. Sleep problems have been noted in 61.8% to 100% of participants in research studies who have SYNGAP1-related Intellectual Disability (ID) which is caused by SYNGAP1 variants. Preliminary work from our research group also found sleep problems in all thirteen individuals whose parents completed a measure called the Children’s Sleep Habits Questionnaire. Although it is clear that poor sleep is a significant issue for those with SYNGAP1-related ID, the nature of sleep patterns in affected individuals is yet to be fully evaluated.

We have neuroscience colleagues who are studying sleep in laboratory models of SYNGAP1-related ID. They have found certain types of seizure around the time of falling asleep and changes in the different stages of sleep. Laboratory researchers in the USA have also found seizure activity during sleep. Our aim is to identify any sleep changes or patterns that are specific to SYNGAP1-related ID by comparing sleep in children with the condition to children who don’t have SYNGAP1-related ID. We will also be able to identify seizure activity or clinical sleep disorders that might require further evaluation or treatment by participants doctor.

Who can participate?
Children (<16 years) with a confirmed SYNGAP1 gene variant, who live in the UK, and can consent, or have a parent or someone with parental responsibility who can consent on their behalf, study partners (siblings, family members, other matched controls).

What does the study involve?
We will meet you and your child/ward by video-link. If they are aged 12 years or over we will assess their ability to decide whether to take part or not. If they lack the ability to consent for themselves or if they are younger than 12 years old, we will seek consent from you if agree to them participating in the study. Legally, children younger than 12 cannot consent for themselves, but we will ask them how they feel about the study. We will do the same for young people over the age of 12 if they can’t consent for themselves. If we are uncertain via video-link if your child/ward has capacity to consent, then a face-to-face appointment will be required to assess this further.
The person giving consent will be able to either sign and return the consent form by post or electronically sign it. When we use video-links during this study we will always use University of Edinburgh approved software/platforms.

If your child/ward has SYNGAP1-related intellectual disability, we will ask you for proof of this from something like a doctor’s letter or genetic testing report.

We will ask you or someone of your choosing who knows your child/ward well to fill in some questionnaires about their health, quality of life and any sleep problems they may have. These questionnaires will take on average around 90 minutes to complete, but don’t have to be filled in all at once. We will also ask for a diary of your child’s sleep to be kept for 7 nights, which will take 5-10 minutes each morning, for 7 days in a row.

We will visit your child/ward’s house to study their sleep for 2 nights using techniques similar to, but less invasive than those used in gold standard sleep evaluations in the NHS. Your child/ward will be asked to wear recording equipment similar to that shown in picture 1 for the overnight recordings. Researchers will visit to help to set up the equipment, but will not need to remain present overnight during data collection. The measurements recorded will include:
• Electroencephalography (EEG – measures electrical activity in the brain)
• Electrooculography (EOG – measures eye movements)
• Electrocardiography (ECG – measures electrical activity in the heart)
• Electromyography (EMG – measures electrical activity in muscle)
• Oxygen levels (SpO2)
• Video – for body position and movements
• Body movement
• Airflow (via nasal cannula)
• Pulse

During our visits researchers will wear appropriate PPE (which is highly likely to include face coverings) and social distancing will be maintained wherever possible. Government guidance and University of Edinburgh specific guidance regarding COVID-19 and other transmissible infections will be followed at all times. All non-invasive, reusable items will be disinfected with alcohol wipes prior to and after use.
As well as studying sleep itself, we are also researching circadian rhythm. This is the daily body rhythm that links to the sleep-wake cycle over roughly each 24 hour period. To measure this, we will ask your child/ward to wear a watch-like device called an actigraph (see picture 2) on a wrist or ankle continuously for a week; it measures activity levels. Our laboratory neuroscience colleagues are also now collecting circadian rhythm data.

What are the possible benefits and risks of participating?
We will be able to tell you more about the sleep and circadian rhythm of participants. We will also be able to tell if we identify specific clinical sleep disorders, sleep-related seizures, and/or circadian rhythm disorders which may require further investigation and treatment. We know that sleep disruption and circadian rhythm disorders can result in problems with learning, memory, behaviour, emotional functioning, and quality of life. Therefore if any treatable cause of sleep disturbance is identified, successful management of it may improve various aspects of the participant's life. With consent, we will inform the participant's doctor(s) about any seizures or sleep problems that may need treatment.

Although at present there is no specific treatment for SYNGAP1-related ID, trials of therapeutics in laboratory models are in progress. If your child/ward takes part in this study, their data will directly assist with the search for biomarkers (specific patterns) of sleep in SYNGAP1-related ID which hopefully will help assess how effective any new therapeutics are.

The risks of taking part are low, but there is a time commitment to the study. We don’t expect participants to suffer any health problems due to taking part in the study. Some participants might find wearing the equipment overnight uncomfortable, it can be removed at any time by themselves or their care-givers. We know that some people can find new experiences or meeting new people anxiety provoking.

Where is the study run from?
University of Edinburgh (UK)

When is the study starting and how long is it expected to run for?
May 2021 to July 2023

Who is funding the study?
This study has been organised/sponsored by the University of Edinburgh (UK). Funding comes from the University’s Simons Initiative for the Developing Brain funded by the Simons Foundation Autism Research Initiative (www.sfari.org) and from The Patrick Wild Centre at the University of Edinburgh which conducts research into Autism, Fragile X Syndrome and Intellectual Disabilities (https://patrickwildcentre.com).

Who is the main contact?
Dr Lindsay Mizen, lmizen@ed.ac.uk

Study website

Contact information

Dr Lindsay Mizen
Principal Investigator

The Patrick Wild Centre
Division of Psychiatry
The University of Edinburgh
Kennedy Tower
Royal Edinburgh Hospital
Morningside Park
Edinburgh
EH10 5HF
United Kingdom

ORCID ID	0000-0002-3540-9717
Phone	+44 131 537 6263
Email	lmizen@exseed.ed.ac.uk

Study information

Eligibility

Locations

Countries of recruitment

• Scotland
• United Kingdom

Study participating centre

Sponsor information

Accord (United Kingdom)
University/education

University of Edinburgh
47 Little France Crescent
Edinburgh
EH16 4TJ
Scotland
United Kingdom

Phone	+44 131 242 3330
Email	enquiries@accord.scot
Website	http://accord.scot/
"ROR"	https://ror.org/01x6s1m65

Funders

Funder type

Research organisation

Results and Publications

Study outputs

Additional files

40932 EVOSIS - Protocol_v2.0_07July2021.pdf

40932 EVOSIS - Detailed Information sheet_PIS_v3.0_22July2021.pdf

Detailed information sheet

40932 EVOSIS - Moderate detail information sheet PIS_v2.0_07July2021.pdf

Moderate detail

40932 EVOSIS - Basic information sheet_PIS_v1.0_09June2021.pdf

Basic

40932 EVOSIS - Information sheet for parents_guardians_v3.0_22July2021.pdf

For parents/guardians

Editorial Notes

19/06/2024: The intention to publish date was changed from 01/05/2024 to 01/11/2024.
29/01/2024: The intention to publish date was changed from 01/01/2024 to 01/05/2024.
02/11/2023: The intention to publish date was changed from 01/10/2023 to 01/01/2024.
29/06/2023: The intention to publish date has been changed from 01/07/2023 to 01/10/2023.
28/07/2022: The following changes were made to the trial record:
1. The overall end date was changed from 31/07/2022 to 31/07/2023.
2. The recruitment end date was changed from 15/07/2022 to 22/07/2022.
3. The plain English summary was updated to reflect these changes.
4. The total final enrolment was added.
18/01/2022: Trial's existence confirmed by University of Edinburgh.