Effects of Methylphenidate on Brain and Cognition in 22q11 Deletion Syndrome
Condition: 22q11.2 Deletion Syndrome
MeSH terms: DiGeorge Syndrome; Syndrome
Study type: Interventional

Summary: 
      Chromosome 22q11.2 deletion syndrome (22q11DS) is a neurogenetic condition associated with a
      high risk of psychiatric disorders, including schizophrenia spectrum disorders. This
      population is characterized by a specific neurocognitive profile and atypical brain
      development. Methylphenidate is a psychostimulant used in the treatment of attention deficit
      with/without hyperactivity (ADHD). Although ADHD is one of the most important co-morbidities
      in 22q11DS, affecting 35-45% of patients, to date only two studies have focused on
      quantifying the efficacy of this treatment in this population. The objective of this study is
      to quantify the improvement in cognitive performance as well as the differences in brain
      connectivity associated with the methylphenidate molecule in a population at risk of
      cognitive impairment and the development of schizophrenia.
    

Detailed description: 
      This study aimed to investigate the effects of methylphenidate (Concerta ®) in patients with
      22q11DS. Outcome is evaluated based on changes in clinical and cognitive measures as well as
      brain connectivity (with magnetic resonance imaging and electroencephalography). Treatment
      benefits are evaluated in an intra-subject design, i.e. performance with/without treatment
      are compared for each patient. Depending on medication history and current psychostimulant
      medication, participants are included either in the consumer group (composed of participants
      with ongoing methylphenidate treatment) or in the naïve group (composed of participants naïve
      to the molecule). To the naive participants the investigators prescribe a 13-day treatment of
      Concerta ® at a weight-adjusted dose of 0.7 mg/kg). The treatment phase begins with a lower
      introductory dose for the first 5 days before moving on to the weight-adjusted dose. The
      effect of treatment on cognitive measures is assessed on day 6, with memory monitoring on
      days 7 and 13. The treatment effect evaluated using clinical measures and questionnaires was
      conducted at the end of the treatment phase to ensure multiple opportunities for observation
      by the participant and caregivers. For consumer participants, the procedure was similar. For
      visits with methylphenidate, participants will be asked to take their usual prescription. In
      order to best follow the procedure of the naïve group, for the visits without
      methylphenidate, the consumer participants were asked to interrupt their usual prescription
      for 13 days. Since many participants usually interrupt their treatment during vacations or
      sometimes on weekends, compliance is not a barrier. For methylphenidate-free visits, a 5-day
      break prior to assessment with cognitive measures will be requested from each participant.
      Again, in order to ensure several opportunities for observation for the participant and
      caregivers, assessments with clinical measures and questionnaires will be conducted at the
      end of the break, on day 13.

      The research hypothesis of this study is that methylphenidate treatment has a beneficial
      effect on clinical and cognitive performance. Scores in the tests evaluating these areas are
      expected to be significantly better than when the tests were administered in the absence of
      the substance. A change in brain connectivity is also expected when the drug is taken,
      tending towards a "normalization" of brain connectivity. Finally, to find the link between
      changes in cognitive measures and changes in brain connectivity is investigated.
    

Intervention name(s): Concerta
Intervention type(s): Drug
Intervention description(s): Evaluation of a treatment of Concerta over a period of 13 days.
Intervention MeSH terms: Methylphenidate
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Intervention model description: Depending on medication history and current psychostimulant medication, participants are included either in the consumer group (composed of participants with ongoing methylphenidate treatment) or in the naïve group (composed of participants naïve to the molecule)
Masking: None (Open Label)
Primary purpose: Other