JASPER Early Intervention for Tuberous Sclerosis

Tuberous Sclerosis Complex (TSC) is a genetic disorder caused by mutations in either the TSC1
or TSC2 genes. The genetic variation results in the growth of non-malignant tumors throughout
the body. Neurodevelopmental disorders, including global developmental delay, intellectual
disability, and autism spectrum disorder (ASD) are very common in children with TSC, although
developmental outcomes can vary widely. Study investigators, over the past several years, has
been studying infants and young children with TSC, and investigators have found that
developmental delays can be identified in the first year of life, and that these delays and
differences can predict a diagnosis of ASD. Currently, there is no specific treatment for the
neurodevelopmental disorders associated with TSC. Based on this information, researchers now
want to know if early intervention can help to improve development and prevent ASD in
children with TSC.

Investigators are studying the effects of early behavioral intervention on developmental
outcomes in infants and toddlers with TSC. The study focuses on social-communication skills,
as these are tightly linked to the development of ASD. The overarching goal of this research
is to improve outcomes in infants with TSC by conducting rigorous, innovative research in
treatment, using both brain and behavioral measures to study the effects of treatment.

Participation requires four on-site assessment visits at UCLA or Boston Children's Hospital,
and 12 weekly behavioral intervention sessions, administered in-person and remotely. Because
this behavioral intervention is parent-mediated, a parent must be available to attend these
sessions. Behavioral assessments generally take up to 4 hours to complete. This study also
uses research EEG. This non-invasive assessment generally takes 30-45 minutes to complete.
After the participant's first assessment, he/she will be randomly assigned to receive
treatment either immediately or in 6 months, with behavioral assessments throughout.
Participants will be involved in the study for a duration of 15-21 months, depending on
randomization.

There are no anticipated risks from this study, although it is possible that the participant
may react negatively to some of the assessment measures or intervention sessions. For
example, at the most extreme, the participant may be fearful of an age-appropriate toy and
may cry or physically pull back from the toy. If this should occur, that particular toy
presentation, assessment or intervention will be stopped. Sometimes the EEG net can feel
uncomfortable, especially if children do not like wearing hats or having anything touch their
heads. Because of this, the study team will provide families with the demonstration
("practice") net to use with the participant before his/her session. At any time during the
session if the participant becomes too upset or agitated, researchers will stop the session.
Loss of confidentiality is a risk of participating in this research study. As described
below, researchers will take every measure to keep participation in this research study
confidential. Participants may benefit from the intervention by receiving detailed
information about your child's cognitive, language, and communication skills both before the
intervention begins and after the intervention is completed. Participants also may benefit
from the intervention itself, which is aimed at improving social communication skills in
infants and toddlers at high risk for neurodevelopmental disorders. Families will receive
written feedback on the participants's performance on the behavioral assessments administered
during assessment time point 4. These assessments are used for research purposes and
therefore are not comprehensive clinical evaluations. Some of the assessments administered
will measure social communication skills relevant to Autism Spectrum Disorder (ASD), and the
feedback letter will report whether the assessment indicated the possible presence of ASD.
The results of the research may also contribute to the broader TSC and autism fields by
enhancing the knowledge of the effects of early intervention on social communication skills
in TSC. Benefits that participating children may derive from the intervention may lead to
greater benefits for all children with autism and/or TSC.

Inclusion Criteria:

- A confirmed diagnosis of Tuberous Sclerosis Complex

Exclusion Criteria:

- A mental age less than 6 months. A plan for epilepsy surgery during the study
participation period.