Rapalogues for Autism Phenotype in TSC: A Feasibility Study

NCT01929642 | Completed Phase 2 Results DMC

• 1 other identifier: AM00037881
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

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.

Conditions

Tuberous Sclerosis Complex; Self-injury; Autism

Keywords

Tuberous Sclerosis Complex (TSC); self-injury; Autism

Outcome Measures

Primary Outcomes (3)

• Number of Participants With Compliance to the Treatment Protocol.

  One outcome measurement of feasibility will include family/patient compliance with the treatment protocol, which will be assessed and documented at every study visit and telephone follow-up call, by the physician and/or study team member. This was calculated by calculating dividing the total number of study visits and study assessments completed by the total number of study visits and study assessments indicated by the treatment protocol.

  Change from baseline to EOT visit 12 week 53

• Caregiver Burden

  The Caregiver Burden Scale is a standard set of questions which will be used to measure the non-medical impact of TSC on caregivers and how it affects the feasibility of study completion. The Caregiver's Burden Scale (CBS) is a 22-item scale that assess subjectively experienced burden by caregiver's to chronically disabled persons. maximum scores: 88 \& Minumum scores: 22 High values represent a worse outcome

  Change from baseline to EOT visit 12 week 53

• Feasibility Measurements of Parental Stress

  Measurements of stress will be administered. Specifically, we will use the Parental Stress Index. Quantifying stress, as well as compliance with the study protocol, will allow investigators to objectively assess the feasibility of a larger clinical trial of sirolimus in patients with TSC. Parental stress index maximum score: 180 Parental stress index minimum score: 36 higher raw scores indicate higher levels of stress.

  Change from baseline to EOT visit 12 week 53

Secondary Outcomes (5)

• Total Number of Aggressions or Self-injuries

  1 year

• Cognitive Function as Assessed by the Capute Scale

  1 year

• Repetitive Behavior

  1 year

• Self-Injury Trauma Scale--SIT Scale

  1 year

• Frequency of Seizures Assessed by Total Number of Seizures

  at baseline

Study Arms (1)

Sirolimus or Everolimus

EXPERIMENTAL

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

Drug: Sirolimus; Drug: Everolimus

Interventions

Sirolimus DRUG

Also known as: Rapamune, Rapamycin

Sirolimus or Everolimus

Everolimus DRUG

Also known as: Afinitor

Sirolimus or Everolimus

Eligibility Criteria

• Age: 2 Years - 30 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Diagnosed with Tuberous Sclerosis Complex as defined by the revised NIH consensus criteria
• Possible autism or autism spectrum disorder and/or possible intellectual disability and/or global developmental delay
• Currently displaying disruptive behaviors, such as self-injury and aggression
• Seizures or epilepsy with at least one seizure within six months prior to enrollment
• years of age
• English-speaking caregiver if participant is non-verbal.
• If individuals are currently being treated with everolimus, they must have been taking it for less than or equal to 6 months.

You may not qualify if:

• 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.
• 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.
• 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.
• Participants who have medical contraindications to undergoing an MRI will be excluded.
• Participants with devices implanted in the brain will be excluded.
• 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.
• Participants who have a history of herpes simplex virus, cytomegalovirus, and/or HIV infection will be excluded

Sponsors & Collaborators

• Hugo W. Moser Research Institute at Kennedy Krieger, Inc.: lead

Study Sites (1)

Kennedy Krieger Institute

Baltimore, Maryland, 21205, United States

Location

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Related Links

• Kennedy Krieger Institute Clinical Trials Unit
• TSC clinic at Kennedy Krieger Institute

MeSH Terms

Conditions

Tuberous Sclerosis; Self-Injurious Behavior; Autistic Disorder

Interventions

Sirolimus; Everolimus

Condition Hierarchy (Ancestors)

Hamartoma; Neoplasms; Neoplasms, Multiple Primary; Neoplastic Syndromes, Hereditary; Malformations of Cortical Development, Group I; Malformations of Cortical Development; Nervous System Malformations; Nervous System Diseases; Neurocutaneous Syndromes; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, Inborn; Behavioral Symptoms; Behavior; Autism Spectrum Disorder; Child Development Disorders, Pervasive; Neurodevelopmental Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals

Results Point of Contact

• Title: Dr. Tanjala Gipson
• Organization: Boling Center for Developmental Disabilities

sbarden@uthsc.edu

901-448-6512

Study Officials

• Tanjala Gipson, MD

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

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 7, 2013
• First Posted: August 28, 2013
• Study Start: July 1, 2013
• Primary Completion: July 1, 2016
• Study Completion: August 1, 2016
• Last Updated: March 29, 2021
• Results First Posted: March 29, 2021

Record last verified: 2021-03

Locations

US (1)