Rapalogues for Autism Phenotype in TSC: A Feasibility Study

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Brief Title

Rapalogues for Autism Phenotype in TSC: A Feasibility Study

Official Title

Rapalogues for Autism Phenotype in TSC: A Feasibility Study

Brief 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.
    

Study Phase

Phase 2

Study Type

Interventional


Primary Outcome

Number of Participants With Compliance to the Treatment Protocol.

Secondary Outcome

 Total Number of Aggressions or Self-injuries

Condition

Tuberous Sclerosis Complex

Intervention

Sirolimus

Study Arms / Comparison Groups

 Sirolimus or Everolimus
Description:  Oral solution or tablet,titrated to therapeutic serum trough range (sirolimus); Oral tablet, titrated to therapeutic serum trough range (everolimus)

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

3

Start Date

July 2013

Completion Date

August 2016

Primary Completion Date

July 2016

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
      

Gender

All

Ages

2 Years - 30 Years

Accepts Healthy Volunteers

No

Contacts

Tanjala Gipson, MD, , 

Location Countries

United States

Location Countries

United States

Administrative Informations


NCT ID

NCT01929642

Organization ID

AM00037881


Responsible Party

Sponsor

Study Sponsor

Hugo W. Moser Research Institute at Kennedy Krieger, Inc.


Study Sponsor

Tanjala Gipson, MD, Principal Investigator, Hugo W. Moser Research Institute at Kennedy Krieger, Inc.


Verification Date

March 2021