A Randomized Double-Blind Controlled Trial of Everolimus in Individuals With PTEN Mutations (RAD001XUS257T)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 46
- 试验地点
- 3
- 主要终点
- Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability], Dropout
研究概览
简要总结
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.
详细描述
This is a signal seeking Phase I/II 6-month, randomized, double-blind placebo-controlled trial of everolimus in individuals, ages 5 to 45 years with a PTEN mutation, with safety and neurocognition as the primary endpoints.
Participant's or a legal guardian will need to sign an informed consent prior to enrollment in the study. To determine eligibility participants will undergo a series of screening tests and safety measures. If determined to be eligible for the blinded phase of the study, participants will be randomly assigned to take either the study drug or a placebo (pill with no medicine).
The blinded phase of the study involves about eight visits, five 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, if optional measures are done, while all other visits will be less than 2 hours. The study visits include blood draws, general health exams, and neuropsychological assessments. The study will also include optional eye-tracking, EEG and auditory evoked potential (AEP) measures, and the collection of microbiome/mycobiome and biomarker blood sample. 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. The open label phase assessments will be similar to those done in the blinded phase, but patients/families will only need to return to the study site three times during this phase.
Participants will receive a developmental assessments report after completing the study. After all study data has been analyzed, patients and families will also be informed of the overall results. Treatment on this study may or may not improve an individual's learning skills (neurocognition) or behavior. We hope that future patients and families will benefit from what is learned by this study.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 5 Years 至 45 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
RAD001
RAD001 is formulated as tablets of 5.0 mg or 2.5mg strength, blister-packed under aluminum foil in units of 10 tablets and dosed on a regular basis.
干预措施: RAD001 (Drug)
Placebo
Matching placebo will be provided as a matching tablet and will also be blister packed under aluminum foil in units of 10.
干预措施: Placebo (Drug)
结局指标
主要结局
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability], Dropout
时间窗: Through study completion, an average of 6 months
The primary endpoint will be safety as measured by study drop-out rate due to side effects, comparing everolimus vs. placebo. We will also determine the frequency of adverse events by type and severity. This section displays participant dropout rate and for what reason.
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability], Adverse Events (AEs) Overview (% of Participants)
时间窗: Through study completion, an average of 6 months
The primary endpoint will be safety as measured by study drop-out rate due to side effects, comparing everolimus vs. placebo. We will also determine the frequency of adverse events by type and severity. this section displays the number of participants who experienced an AE and the description of such AEs, pertaining to: 1. Seriousness 2. Grade, 3. Relation to treatment 4. Recovery from AE 5. Category
次要结局
- Change at 6 Months in Composite Score(6 months)
- Change in Processing Speed at 6 Months, Conner's Continuous Performance Test (CPT)-3(6 months)
- Change in Fine Motor Skills at 6 Months, Purdue Pegboard(6 months)
- Change in Global Cognitive Ability at 6 Months, Stanford-Binet Intelligence Scales, Fifth Edition (SB-5) or Mullen Scales of Early Learning(6 months)
- Change in Motor Functioning at 6 Months, Purdue Pegboard and Developmental Coordination Disorder Questionnaire (DCDQ)(6 months)
- Change in Memory, Executive Functioning, Autism Symptoms, Adaptive Behaviors, and Other Behaviors at 6 Months(6 months)
研究者
Mustafa Sahin
Director, Translational Neuroscience Center/ Professor of Neurology, Harvard Medical School
Boston Children's Hospital