None listed
Conditions
Brief summary
The increasing prevalence of neurodevelopmental disorders is a global concern. Autism spectrum disorder (ASD) affects approximately 1/100 children worldwide. More so, sleep disorders (SD) co-occurring with autistic traits have been more frequently reported in 40-80% of children diagnosed with ASD. These symptom constellations are strongly associated with concomitant parental stress, reduced quality of life and an economic burden to family and society. Consequently, the National Sleep Foundation identifies children with ASD as one of the highest-priority populations for sleep research. Several risk factors have been identified in the aetiologies of ASD and SD. For instance, abnormal organisation and maturation of grey matter have been linked to a negative correlation to sleep architecture. Other studies indicate that an imbalance in GABAergic and glutamatergic systems disrupts neural signalling and development with corresponding presentations of ASD behaviours linked to SD. A study suggested a correlation between more severe core ASD symptoms in children and disruption in sleep architecture. Interventions that target these shared pathologies could hold clinical benefits for ASD and SD outcomes. Repetitive Transcranial magnetic stimulation (rTMS) is an intervention of interest due to its effect on abnormal brain functions implicated in ASD. rTMS is a non-pharmacological and non-invasive brain stimulation that uses the magnetic field generated from an electromagnetic coil placed on the scalp to alter neural structures and functions. Its clinical potential has been demonstrated in several neurological conditions, with FDA approval for use in depression. A recent study demonstrated rTMS to be effective and safe in children with ASD and SD. The study showed improved sleep outcomes based on the children's sleep habit questionnaire (CSHQ) following the use of the same rTMS protocol across participants. Such one-shoe-size-fits-all (standard) treatment approaches are thought to limit the optimisation of rTMS potential, especially within a heterogeneous population. The heterogeneous characteristics such as individual alpha frequency (IAF), stimulation frequency, and age are known determinants of the intervention outcome. A chart study of IAF-guided rTMS documented improvement in ASD symptoms and sleep outcomes. Consequently, there is a sparse study on the efficacy and safety of IAF-guided rTMS in children with ASD and SD. This study aims to evaluate the efficacy and safety of IAF-guided rTMS on ASD symptoms and comorbid SD and quality of life in children and their primary caregivers based on pre-post objective and subjective measures. For the primary outcome, the study hypothesis is that IAF-guided rTMS improve sleep quality and quantity and other SD parameters. The study design is a randomised, waitlist-controlled, open-label pilot trial.
Interventions
The intervention is a planned, personalised treatment that uses individual alpha frequency (IAF) to guide repetitive transcranial magnetic stimulation (rTMS) protocol towards optimising outcomes due to the heterogeneous nature of sleep difficulties and an autism spectrum disorder.
Electroencephalogram/electrocardiogram (EEG/ECG) conducted by a trained technician (with over two years experience) on the TruScan acquisition software (Deymed diagnostic, s.r.o, Czech Republic) will be used to dete
The intervention is a planned, personalised treatment that uses individual alpha frequency (IAF) to guide repetitive transcranial magnetic stimulation (rTMS) protocol towards optimising outcomes due to the heterogeneous nature of sleep difficulties and an autism spectrum disorder. Electroencephalogram/electrocardiogram (EEG/ECG) conducted by a trained technician (with over two years experience) on the TruScan acquisition software (Deymed diagnostic, s.r.o, Czech Republic) will be used to determine the participant's IAF, stimulation frequency and location. Briefly, EEG/ECG will be conducted under eyes closed conditions, and the recorded time series will be converted to the frequency domain using Fast Fourier Transform (FFT). The stimulating frequency will be determined by identifying the dominant peak frequency with the highest power in the 8-13Hz range and multiplying it by the higher harmonic frequency (5th to 10th) of the ECG nearest to the dominant peak frequency. The stimulation location will be the brain region with the highest aberrant cortical processes compared to a normative database with equal parameters and measured using the 10-20 system. The EEG/ECG will be conducted at baseline, posttreatment (post-completion of a two-week treatment program) and follow-up (one and four months posttreatment) periods of both treatment and control groups. Data from the IAF, stimulation frequency, and location will be used by the trained technician in personalising the rTMS protocol for each participant. The rTMS is a 5-second stimulation train with pulses to be delivered at the determined stimulation frequency with 28-second intervals between 32 trains per-determined cortical location using an MCF-B65 butterfly coil and Magpro R30 TMS stimulator. The rTMS will be used to determine the resting motor threshold (RMT) by placing the centre of the coil on the motor cortex of the participant and gradually increasing the output of the TMS machine by 5% until a visible twitch in the muscle of the contralateral fingers is observed in two out of three trials. The output intensity of IAF-guided rTMS (if found) will be administered at 80% (RMT) to minimise potential side effects. If the RMT is not found, rTMS will be delivered at 50% and 40% output intensity at the frontal and posterior brain regions, respectively. A session of IAF-guided rTMS will be administered to both active and control groups each weekday for two weeks (I.e., ten sessions in total). Each daily session last approximately 40mins. The intervention is to be delivered within an outpatient clinic. Participants' adherence to the intervention will be documented by the treatment technician during each clinic visit using a self-designed treatment log. The treatment log will report the number of sessions delivered, the output intensity, frequency and location of treatment, sleep onset and awake times, and other feedback from primary caregivers on any distinct observed behavioural changes, side effects from previous sessions.
Sponsors
Uchenna Ezedinma
Study design
Allocation
Randomised controlled trial
Intervention model
Other
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
6 Years to 12 Years
Healthy volunteers
No
Inclusion criteria
i. Children aged 6-12 years with a valid diagnosis of ASD (level 2) and SD, and their primary caregivers, ii. Meet the definition of sleep difficulties based on the clinical cut-off of >41 on the Children's Sleep Habits Questionnaire (CSHQ). iii. Children who can complete pre-assessment EEG and polysomnography (level 2 home sleep study).
Exclusion criteria
Co-diagnosis of congenital conditions such as Down syndrome. ii. Child with a reported history of rTMS use. iii. Child with diagnosed nocturnal seizures, blindness, and moderate-severe obstructive sleep apnoea (OSA). iv. Child with body implants such as pacemaker, Defibrillator, Vagal Nerve Stimulator, VP Shunt/ Magnetic intracranial shunts, Deep Brain Stimulator, Epidural Cortical stimulator, Steel shunts/stents, Cranial metal fragments (i.e. shrapnel, excluding titanium), Cochlear implant, aneurysm clips, coils, pipelines flow diversion, magnetic dental implants, Implanted cardioverter defibrillators (ICD), and Ocular implants v. Child that is still breast feeding. vi. Child with primary brain cancer / metastatic legions in the brain (unless palliative care)
Outcome results
None listed