Early Interventions in Children With Attention Deficit/Hyperactivity Disorder
Condition: Attention Deficit Disorder With Hyperactivity; Preschool Child
MeSH terms: Hyperkinesis; Attention Deficit Disorder with Hyperactivity
Study type: Interventional
Phase: Phase 4

Summary: 
      Introduction: Attention deficit/hyperactivity disorder (ADHD) is one of the most prevalent
      mental disorders in children and is associated with important negative functional outcomes
      throughout development. The first signs and symptoms become apparent in preschool age.
      Therefore, early interventions in this population have the potential of limiting the
      disorder's negative impact and preventing future impairments in affected individuals. The
      first-choice medication for treating ADHD is methylphenidate, which has evidence of efficacy
      and safety in preschool children. However, non-evidence based worries and pressure from the
      media placed parent training as the first-line treatment for ADHD in clinical guidelines.
      Parent training is a behavioral intervention implemented with the parents, with weekly
      sessions for 8 weeks, adequate for treating ADHD dysfunctional symptoms and behaviors.
      However, the level of evidence for this intervention is reduced. Furthermore, the need of
      trained therapists in the public health system, added to the difficulties on adherence and
      comprehension from parents, limit its generalization and raise questions regarding its
      indications. Until now, no study has compared pharmacological treatment with methylphenidate
      to parent training in preschool children with ADHD regarding their clinical efficacy and
      cost-effectiveness. Moreover, no study has evaluated the impact of pharmacological
      intervention and psychotherapy on neurobiological mechanisms of ADHD, which is crucial for
      determining their impact on neurodevelopment.

      Objectives: This is a double-blind randomized clinical trial that aims to evaluate the
      efficacy, tolerability, and acceptability of treatment with methylphenidate compared to
      parental training and placebo in preschool children with ADHD.

      Methods: This study will be a randomized, double-blind, parallel-group, evaluating two active
      interventions and placebo control group. One hundred and fifty children aged 3 years and 11
      months and 5 years and 11 months, diagnosed with ADHD, will be randomized to receive
      treatment with methylphenidate and information (50 children), parental training and treatment
      with placebo medication (50 children) or belong to active control group with educational
      information for parents and placebo treatment with no treatment (active control, 50
      children). The treatment will last eight weeks, the neurobiological outcomes will be assessed
      before and after treatment and clinical outcomes will be assessed at weeks 0, 5 and 9. After
      the end of treatment, all participants will be invited to participate in a 3 years' annual
      follow-up. 50 children with typical development will also be evaluated in relation to
      neurobiological measures.

      Implications: This study proposes an innovative and relevant analysis, which will enable the
      field to advance the knowledge of biological mechanisms related to ADHD and to treatment
      response. Also, the study will expand the evidence to guide early prevention strategies and
      early intervention.
    

Detailed description: 
      The recruitment of participants will be performed through social media divulgation, on our
      official website and through contact with preschools in the city of Sao Paulo. The
      participants that have been selected on the telephonic pre-screening are called for a
      diagnostic evaluation and an eligibility criteria verification performed by a child and
      adolescence psychiatrist and neuropsychologists. The psychiatric care and the outcomes
      evaluation sessions will be conducted by trained professionals, under the principal
      investigator's supervision.

      The children will be randomized using the website randomization.com to one of the three
      groups: drug treatment with methylphenidate and educational information, parental training
      and placebo medication, or active control group with educational information and placebo
      medication. After the eight-week intervention, the participants can receive treatments not
      previously offered according to a clinical decision.

      All selected participants for the clinical trial will be evaluated and accompanied by a child
      and adolescent psychiatrist before the study and bi-weekly until its completion. Furthermore,
      a blind evaluator will be responsible for the outcomes measures evaluation.

      The clinical evaluator (child and adolescent psychiatrist) and the research assistant
      responsible for the questionnaires application will be blind towards the modality of
      treatment that the participant undergoes.

      All of the study's evaluation protocol and monitoring is done on the platform Research
      Electronic Data Capture - REDCap, a software developed by Vanderbilt University - Tennessee,
      which is hosted in The Clinics Hospital of the University of São Paulo Medical School server.
      REDCap presents three main functions: a) electronic data collection; b) data management; c)
      study flow management. This data bank complies with the international policies of data's
      privacy and security on health area. In addition to the collection and storage structure,
      validation, auditing and data exporting tools of the system itself are also used.

      The efficacy analysis will be made from treatment intention (data from all randomized
      patients will be included in the analysis). The outcomes (clinical measures of efficacy and
      tolerability) will be analyzed through mixed effects analyses, with individual models for
      each outcome. This model assumes that missing data occurs at random and avoids potential
      biases associated with the analysis only of the individuals who completed the observations or
      using the strategy to carry the last observation made. The model will include fixed effects
      for treatment (three levels), time (0, 5 and 9 weeks), time-treatment interaction and
      randomization effect for the participants. Effect sizes will be calculated by subtracting of
      the modification of each of the outcomes between the patients in the active groups versus
      active group control, and between both active treatments, divided by the standard deviation
      of the entire sample.
    

Intervention name(s): Methylphenidate; Parental training; Psychoeducational groups for parents; Placebo pill
Intervention type(s): Drug; Behavioral; Other; Drug
Intervention description(s): Methylphenidate treatment with a initial dosage of 0,3 mg/kg per day (weekly dosage adjustments).; Weekly parental training conducted by behavioral psychologists.; Weekly psychoeducational groups conducted by educators.; Placebo pill during 8 weeks.
Intervention MeSH terms: Methylphenidate
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Parental training; Preschool age; Attention Deficit/Hyperactivity Disorder (ADHD)