Clinical Trial: RAD001 and Neurocognition in PTEN Hamartoma Tumor Syndrome (PTEN)

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: A Randomized Double-Blind Controlled Trial of Everolimus in Children and Adolescents With PTEN Mutations (RAD001XUS257T)

Brief Summary: Phosphatase and TENsin homolog (PTEN) gene germline mutations are associated with a spectrum of clinical manifestations characterized by neurocognitive deficits, intellectual disability, autism symptomatology, skin lesions, macrocephaly, hamartomatous overgrowth of tissues, and an increased risk of cancers. Investigators are conducting research to evaluate the potential safety and efficacy of RAD001 (everolimus) in this patient population, and the potential neurocognitive benefits from treatment with RAD001 or placebo for a six month period. The investigators hope this trial will lead to a better understanding of PTEN and to new forms of treatment that may benefit children and adults with PTEN in the future.

Detailed Summary:

This is a signal seeking Phase I/II 6-month, randomized, double-blind placebo-controlled trial of RAD001 in children and adolescents, ages 6 to 21 years with a PTEN mutation, with safety and neurocognition as the primary endpoints.

Prior to enrolling in the study and undergoing a series of screening tests to confirm eligibility, the participant or a legal guardian will need to sign an informed consent. If determined to be eligible for the treatment phase of the trial, participants will be randomly assigned to take either the study drug or a placebo (pill with no medicine).

The study involves about nine visits, six of which will occur at the study site, and three of which will be conducted over the phone. These visits will take place over a six month period. Study visits will vary in length. Baseline, three month and six month visits may last up to 8 hours, while all other visits will be less than 2 hours. The study visits include blood draws, laboratory tests and neuropsychological assessments. The study will also include eye-tracking, the collection of EEG data, and the option to participate in microbiome sample collections. There is no fee to participate in this study. The study drug will be provided at no charge during the study.

After the 6 month treatment phase, individuals who were randomly assigned to take placebo will be offered inclusion in a 6 month open label phase where the study drug will be provided at no charge and assessments will continue as they did in the initial 6 month period.

After all study data has been analyzed, families will be informed of the overall results. Treatment on this study may or may not improve a child's learning skills (neurocognition). Future patients may benefit from what is learned.<
Sponsor: Boston Children’s Hospital

Current Primary Outcome: Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] [ Time Frame: Through study completion, an average of 6 months ]

Original Primary Outcome: Same as current

Current Secondary Outcome:

• Change in Working Memory at 6 Months [ Time Frame: 6 months ]
  Working memory will be evaluated using the Stanford Binet 5 or Mullen Scales of Early Learning at 6 months
• Change in Processing Speed at 3 Months [ Time Frame: 3 months ]
  Processing speed will be evaluated using mean reaction time on the Conner's Continuous Performance Test (CPT)-3.
• Change in Processing Speed at 6 Months [ Time Frame: 6 months ]
  Processing speed will be evaluated using mean reaction time on the Conner's Continuous Performance Test (CPT)-3.
• Change in Fine Motor Skills at 3 Months [ Time Frame: 3 months ]
  Fine motor skills will be evaluated using the Purdue Pegboard sub-tests average of both hands
• Change in Fine Motor Skills at 6 Months [ Time Frame: 6 months ]
  Fine motor skills will be evaluated using the Purdue Pegboard sub-tests average of both hands
• Change in Attention at 3 Months [ Time Frame: 3 months ]
  Attention will be measured by Conners' Continuous Performance Test - 3 - Discriminability index (d') and Omissions
• Change in Attention at 6 Months [ Time Frame: 6 months ]
  Attention will be measured by Conners' Continuous Performance Test - 3 - Discriminability index (d') and Omissions
• Change in Impulsivity at 3 Months [ Time Frame: 3 months ]
  Impulsivity will be measured by Conners' Continuous Performance Test-3- Commissions and Bias (B').
• Change in Impulsivity at 6 Months [ Time Frame: 6 months ]
  Impulsivity will be measured by Conners' Continuous Performance Test-3- Commissions and Bias (B').
• Change in Global Cognitive Ability at 6 Months [ Time Frame: 6 months ]
  Change in global cognitive ability will be measured by Stanford-Binet 5 or Mullen; Full scale, verbal and nonverbal ability (IQ)
• Change in Motor Functioning at 3 Months [ Time Frame: 3 months ]
  Motor functioning will be measured by the Purdue Pegboard (Pegs): Dominant and non-dominant hand combined standard scores and Developmental Coordination Disorder Questionnaire (DCDQ): Total score.
• Change in Motor Functioning at 6 Months [ Time Frame: 6 months ]
  Motor functioning will be measured by the Purdue Pegboard (Pegs): Dominant and non-dominant hand combined standard scores and Developmental Coordination Disorder Questionnaire (DCDQ): Total score.
• Change in Communication Ability at 3 Months [ Time Frame: 3 months ]
  Communication ability will be measured by using standard scores of the Peabody Picture Vocabulary Test (PPVT-4), Expressive Vocabulary Test (EVT-2)
• Change in Communication Ability at 6 Months [ Time Frame: 6 months ]
  Communication ability will be measured by using standard scores of the Peabody Picture Vocabulary Test (PPVT-4), Expressive Vocabulary Test (EVT-2)

Original Secondary Outcome: Same as current

Information By: Boston Children’s Hospital

Dates:
Date Received: December 2, 2016
Date Started: May 2017
Date Completion: June 2019
Last Updated: May 11, 2017
Last Verified: May 2017