Frameshift Peptides of Children With Neurofibromatosis Type 1 (NF1) and Either Low-Grade Gliomas or Plexiform Neurofibromas
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 60
- 试验地点
- 3
- 主要终点
- Measure mean florescent intensity of serum/plasma samples for each cohort by assaying the study samples on frameshift peptide arrays consisting of peptides representing the ~220,000 frameshifts tumors can make in RNA processing.
研究概览
简要总结
The objective of this study is to determine if children and young adults with Neurofibromatosis Type 1 (NF1) and either Low Grade Gliomas (LGGs) or Plexiform Neurofibromas (PNs) have a specific frameshift peptide protein profile and whether a disease specific vaccine created to address these frameshift mutations and variants can be developed. Three study populations will be analyzed; patients with NF1 and active LGGs, NF1 and active PNs, and NF1 and no evidence of active LGGs or PNs. Participation involves a onetime blood draw.
详细描述
I. Objective and Specific Aims
A. Objectives:
To determine if children and young adults with NF1 and either Low Grade Gliomas (LGGs) or Plexiform Neurofibromas (PNs) have a specific frameshift peptide protein profile and whether a disease specific vaccine created to address these frameshift mutations and variants can be developed.
B. Primary Aims:
- Determine the frameshift peptide profile of children and young adults with NF1 and active LGGs, NF1 and active PNs, and NF1 and no evidence of active LGGs or PNs.
- Determine if the frameshift peptide profiles of children and young adults with NF1 in each of the populations of interest differ.
- Determine if specific frameshift peptide profiles can be used to create a disease specific vaccine for children and young adults with NF1 and either LGGs or PNs.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 1 Day 至 30 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subjects must be between 1 day and 30 years of age, inclusive
- •Subjects must either meet clinical criteria for NF1 or have molecular genetic germ line evidence of NF1
- •Subject is able to have his/her blood sample drawn within a reasonable period of time after signing consent
- •Subjects must either have:
- •Active* LGGs, no active PNs (Cohort 1)
- •Active* PNs, no active LGGs (Cohort 2)
- •No active* LGGs or PNs (Cohort 3) *Active is defined as any LGG or PN that has shown growth (determined by MRI) in the past 12 months or is causing ongoing symptomatic visual, neurologic, or organ dysfunction or disfigurement as determined by the site investigator.
排除标准
- •Patients with NF1 with evidence of both LGG and PN
结局指标
主要结局
Measure mean florescent intensity of serum/plasma samples for each cohort by assaying the study samples on frameshift peptide arrays consisting of peptides representing the ~220,000 frameshifts tumors can make in RNA processing.
时间窗: 2 years
All samples will be assayed on the FSP arrays consisting of peptides representing the frameshifts tumors can make in RNA processing. The amount of IgG bound to each feature will be determined as florescent intensity generated by bound secondary antibody. The mean intensity across the 20 subjects for each peptide for each of the 3 groups will be determined. All peptides in the NF1+LGG group with mean intensities greater than 3 SD higher than the mean of the NF1-LGG/PN group will be determined. Those that meet this criterion in more than 3 of the 20 samples will be chosen. The 20 peptides with the highest prevalence across the 20 samples of NF1+LGG will be chosen for the vaccine. If two peptides have the same prevalence, the one with the highest average florescence will be chosen. The same procedure will be applied to determine the 20 peptide components for the NF1+PN vaccine.
Use a feature counting method to establish a mean distinguishable frameshift peptide protein profile for early detection of tumors in patients with NF1.
时间窗: 2 years
The same data as generated in Outcome 1 will be analyzed for the ability to distinguish NF1+LGG and NF1+PN samples from the NF1-LGG/PN samples. Since the antibody reactions to frameshift peptides are stochastic, a feature counting method is employed. A mean is established for each of the NF1-LGG/PN peptides. Any peptide in the NF1+LGG and NF1+PN samples that scores 3 SD higher than NF1-LGG/PN mean is scored as a positive. The total number of positives in the NF1+LGG and NF1+PN pool will be compared to that in the NF1-LGG/PN set. The number of samples that are distinguished by these counts will determine a first pass accuracy estimate of this diagnostic approach as a preamble to an expanded study.
Use a feature counting method to establish a mean distinguishable frameshift peptide protein profile for patient who develop LGGs versus patients who develop PNs.
时间窗: 2 years
The same array data generated in Outcome 1 will be used. The feature counting method used in Outcome 2 will be used to compare the NF1+LGG features to the NF1+PN features. The investigators will determine if there are a set of features that can distinguish the 20 NF1+LGG from the 20 NF1+PN samples. The number of NF1+LGG and NF1+PN samples that can be distinguished will provide a first estimate of accuracy and whether an expanded study is merited.
次要结局
- Correlate age, gender, family history of NF, disease state (stable, progressive, or improving), and disease history with frameshift peptide profiles, in children and young adults with NF1 and LGGs or PNs.(2 years)
研究者
Roger Packer
Senior Vice President of Neurology and Behavorial Medicine
Children's National Research Institute