Stimulant Medication for ADHD and Tics - Understanding Response versus Non-stimulants (SATURN study): a randomised trial of the clinical and cost-effectiveness of methylphenidate versus guanfacine for ADHD in children and young people with a co-existing tic disorder

RESEARCH QUESTION What is the clinical and cost-effectiveness of stimulant compared with non-stimulant medication for children and young people (CYP) with ADHD and co-existing tics? BACKGROUND Around 3-5% of CYP have attention deficit hyperactivity disorder (ADHD) and around 1 in 5 of these will also experience chronic ‘tics’, which consist of uncontrolled, sudden movements of the body and sounds. Early treatment is crucial to help the person cope and reduce the impact on the family and wider social and healthcare systems. Medication for ADHD is highly effective and the clinically recommended first-line medication is methylphenidate, which is a stimulant. However, there is concern amongst clinicians that using stimulant medication to treat young people with ADHD and tics may make the young person’s tics worse. As a result of this, many clinicians prefer to prescribe non-stimulant medication, which may not be as effective for treating the ADHD symptoms. AIMS AND OBJECTIVES The aim of this research is to understand whether stimulant or non-stimulant medication is most effective for treating children and young people who are experiencing both ADHD and tics.ADHD symptoms and tics are joint primary outcomes; therefore, the trial is powered for both outcomes. We aim to test whether stimulant compared with non-stimulant medication is: a) superior for ADHD symptoms: stimulants should result in a clinically important improvement in ADHD symptoms. b) non-inferior for tics: stimulants should not result in a clinically important worsening with respect to tics. METHODS Design: Two-arm parallel group randomised comparative trial. The co-primary outcomes (ADHD symptoms and tics) will be measured at 12 weeks. The treatment period is 12 months. Anyone wishing to stop or change their allocated medication will be free to do so with any changes recorded. All participants, whether persisting with allocated medication or not, will be followed up for 12 months unless they withdraw consent. Participants' medication will be monitored by the trial team for the 12-month duration. Setting: NHS CAMHS and community paediatric clinics in England. Study population: CYP with ADHD and co-existing tics. Sample size: 314 participants (157 per arm), recruited over 24 months from 3 regional Hubs across England. Randomisation: Eligible patients who consent (age under 16: parental consent, young person’s assent; age 16-17: young person’s consent) will be allocated on 1:1 ratio to receive either stimulant (modified-release methylphenidate) or non-stimulant medication (guanfacine). Randomisation will be stratified by site. TIMELINES FOR DELIVERY Month (M) 1-8: Protocol development, approvals by Medicines and Healthcare products Regulatory Agency (MHRA), database development, site set-up and training. M 9-18: Internal pilot recruitment. M19: Internal pilot progression review by Trial Steering Committee (TSC)/ Data Monitoring and Ethics Committee (DMEC) and report to sponsor & funder. M 20-32: Complete recruitment, target average 15 patients/month, 3 hubs across England. M 20-44: 12-month follow-up completed (First Person Last Visit – Last Person Last Visit). M45: Final data cleaning and data lock. M 45-50: Analysis and write-up of results. M 50: Final Report submission. ANTICIPATED IMPACT AND DISSEMINATION This research will result in high impact peer-reviewed publications, including a full report in the NIHR HTA Journal. We anticipate that results will support a NICE ADHD Evidence Update as the HTA 18/116 call was in response to a NICE research recommendation (NG87 [15]). We will present the findings at national and international conferences, as well as service user/ voluntary sector organisations. We will hold events for NHS providers, commissioners and clinicians.