Rapalogues for Autism Phenotype in TSC: A Feasibility Study
Condition: Tuberous Sclerosis Complex; Self-injury; Autism
MeSH terms: Tuberous Sclerosis; Sclerosis; Autistic Disorder; Self-Injurious Behavior
Study type: Interventional
Phase: Phase 2

Summary: 
      The purpose of this study is to assess the feasibility and safety of administering
      rapalogues, sirolimus or everolimus, in participants with Tuberous Sclerosis Complex (TSC)
      and self-injury and to measure cognitive and behavioral changes, including reduction in
      autistic symptoms, self-injurious and aggressive behaviors, as well as improvements in
      cognition across multiple domains of cognitive function.
    

Detailed description: 
      This is a feasibility and safety study primarily designed to assess the feasibility and
      safety of conducting a larger clinical trial with sirolimus in individuals with TSC. The
      present study will employ an ABA design in which three pediatric participants will be
      selected to receive baseline medical, developmental, behavioral, and cognitive evaluations,
      followed by a 26 week administration of sirolimus, repeated baseline assessments at the end
      of the 26 week treatment phase, and a 4 week titrated withdrawal followed by a 22 week period
      in which no rapalogue is administered. All participants will again be administered baseline
      medical, behavioral, and cognitive evaluations at the end of the study in order to compare
      all evaluations done at baseline, the end of the 26 week treatment, and completion of the
      study. These comparisons will be done to assess secondary outcomes that include reductions in
      autistic symptoms, self-injury, and aggression, as well as improvements in cognitive function
      across multiple domains. Furthermore, administration of the secondary outcome measures will
      also allow us to better understand the sensitivity of these measures in patients with TSC
      during the course of a clinical trial.

      Families of potentially eligible children who express interest in the study and meet
      prescreening criteria will be invited to attend a screening visit to determine eligibility,
      inclusion/exclusion criteria, and availability for eight additional study visits. Prior to
      enrollment, informed consent will be obtained from the parent or legal guardian.

      Investigators will use the methods of analysis of single-subject research (ABA design, where
      first A represents baseline, B represents treatment, and A represents reversal of treatment.
      The analysis will focus on each of the 3 subjects separately. Data on feasibility and safety
      (primary outcome) and on frequency of disruptive behavior (secondary outcome) will be plotted
      and visually inspected to detect any temporal changes by phase: 1. Baseline, 2. Treatment, 3.
      After treatment. Data in each phase will be summarized as mean +/- standard deviation (SD).
      We will use the summary data to assess the potential effect of the intervention. Consistency
      of the effect will be examined across the 3 study participants.
    

Intervention name(s): Sirolimus; Everolimus
Intervention type(s): Drug; Drug
Other intervention name(s): Rapamune, Rapamycin; Afinitor
Intervention MeSH terms: Sirolimus; Everolimus
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Tuberous Sclerosis Complex (TSC); self-injury; Autism