title: Advancing non-invasive neuromodulation clinical trials in children: Lessons from perinatal stroke.
abstract: Applications of non-invasive brain stimulation including therapeutic neuromodulation are expanding at an alarming rate. Increasingly established scientific principles, including directional modulation of well-informed cortical targets, are advancing clinical trial development. However, high levels of disease burden coupled with zealous enthusiasm may be getting ahead of rational research and evidence. Experience is limited in the developing brain where additional issues must be considered. Properly designed and meticulously executed clinical trials are essential and required to advance and optimize the potential of non-invasive neuromodulation without risking the well-being of children and families. Perinatal stroke causes most hemiplegic cerebral palsy and, as a focal injury of defined timing in an otherwise healthy brain, is an ideal human model of developmental plasticity. Advanced models of how the motor systems of young brains develop following early stroke are affording novel windows of opportunity for neuromodulation clinical trials, possibly directing neuroplasticity toward better outcomes. Reviewing the principles of clinical trial design relevant to neuromodulation and using perinatal stroke as a model, this article reviews the current and future issues of advancing such trials in children.
authors.affiliation: Departments of Pediatrics and Clinical Neurosciences, Cumming School of Medicine, Hotchkiss Brain Institute and Alberta Children's Hospital Research Institute, 2888 Shaganappi Trail NW, Calgary, AB T3B6A8, Canada. Electronic address: adam.kirton@albertahealthservices.ca.
authors.forename: Adam
authors.initials: A
authors.lastname: Kirton
mesh_terms: D001921:Brain / Q000502:physiology; D002547:Cerebral Palsy / Q000503:physiopathology / Q000628:therapy; D002648:Child; D002986:Clinical Trials as Topic; D003131:Combined Modality Therapy; D004599:Electric Stimulation Therapy / Q000379:methods*; D006801:Humans; D007231:Infant, Newborn; D007232:Infant, Newborn, Diseases / Q000503:physiopathology / Q000628:therapy*; D009473:Neuronal Plasticity / Q000502:physiology; D020521:Stroke / Q000503:physiopathology / Q000628:therapy*; D050781:Transcranial Magnetic Stimulation / Q000379:methods; D057170:Translational Research, Biomedical
keywords: Brain stimulation; Cerebral palsy; Clinical trials; Developmental plasticity; Neuroplasticity; Perinatal stroke; Transcranial direct current stimulation; Transcranial magnetic stimulation