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
Intervention: Sirolimus; Everolimus
Intervention MeSH terms: Sirolimus; Everolimus
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 3.0
Sex: All
Minimum age: 2 Years
Maximum age: 30 Years
Healthy volunteers: No
Keywords: Tuberous Sclerosis Complex (TSC); self-injury; Autism

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.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Diagnosed with Tuberous Sclerosis Complex as defined by the revised NIH consensus
             criteria

          2. Possible autism or autism spectrum disorder and/or possible intellectual disability
             and/or global developmental delay

          3. Currently displaying disruptive behaviors, such as self-injury and aggression

          4. Seizures or epilepsy with at least one seizure within six months prior to enrollment

          5. 2-30 years of age

          6. English-speaking caregiver if participant is non-verbal.

          7. If individuals are currently being treated with everolimus, they must have been taking
             it for less than or equal to 6 months.

        Exclusion Criteria:

          1. Participants who require live vaccines that are contraindicated with sirolimus will be
             excluded - bacille Calmette Guerin(BCG), measles-mumps-rubella vaccine(MMR),
             poliovirus, rotavirus, smallpox, typhoid, varicella, or yellow fever.

          2. Participants who have a history of multiple or severe infections, or reside in a
             household with anyone who has a chronic, contagious condition will be excluded.
             Multiple infections will be defined as eight or more lifetime episodes of otitis media
             or two or more lifetime episodes of bacterial pneumonia. Severe infections will be
             defined as infections requiring more than one hospital admission for treatment.

          3. Participants with any of the following laboratory abnormalities will be excluded:
             hematocrit < 27%, absolute neutrophil count(ANC) < 1,500, platelet count < 100,000,
             serum glutamate oxaloacetate transaminase(SGOT) or serum glutamate pyruvate
             transaminase (SGPT) > two times normal for age, bilirubin > two times normal for age,
             alkaline phosphatase > two times normal for age, epidermal growth factor receptor
             (eGFR) < 30, or evidence of renal failure, hypercholesterolemia.

          4. Participants who have medical contraindications to undergoing an MRI will be excluded.

          5. Participants with devices implanted in the brain will be excluded.

          6. Pregnant participants will be excluded. All young ladies of child bearing potential
             will have a blood test for pregnancy prior to the start of the study and every study
             visit for the duration of the study.

          7. Participants who have a history of herpes simplex virus, cytomegalovirus, and/or HIV
             infection will be excluded