Astronaut Vision Issues and One Carbon Metabolism: Expanded Polymorphism Evaluation and Evaluation in a Potential Analog Population
试验速览
- 阶段
- 不适用
- 状态
- 进行中（未招募）
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- Ophthalmologic exam - US
研究概览
简要总结
The investigators have documented a genetic predisposition for some astronauts to develop ophthalmologic issues (e.g., choroidal folds, cotton wool spots, optic disc edema). Women with polycystic ovary syndrome (PCOS) have several characteristics similar to those described in astronauts, including: higher homocysteine concentrations, increased incidence of intracranial hypertension, increased retinal nerve fiber layer thickness, increased incidence of white matter hyperintensities on MRI, increased androgen concentrations (or androgen responses to space flight), and indices of altered carbohydrate metabolism. Women with PCOS have not been evaluated in detail regarding the occurrence of other anomalies observed in astronauts including choroidal folds, optic disc edema and cotton wool spots as well as changes in cycloplegic refraction, and optic nerve sheath diameter. While researchers have evaluated one-carbon metabolism pathway polymorphisms re: PCOS, and initial studies show an association with certain one-carbon polymorphisms, none have looked at the complete set of SNPs proposed here. This study will evaluate women with PCOS and/or idiopathic intracranial hypertension (IIH) to assess one-carbon biochemistry and genetics and their possible correlation with ophthalmologic findings. The investigators aim to clarify the relationship of one carbon metabolism and ophthalmic findings in astronauts and patients with PCOS and/or IIH.
详细描述
Evidence from initial analysis of 5 SNPs in the one-carbon metabolism pathway suggests that one-carbon pathway genes may predict risk of ocular changes and possible vision impairment during and after long-duration space flight. It is not precisely known whether it is these particular genes, or a haplotype of genes that are linked to these genes, that influence risk. Furthermore, ancestry is a strong factor that predicts SNP occurrence in a population, and the association between one-carbon metabolism and the risk of vision-related issues may simply stem from the fact that one particular ancestry has a higher prevalence of these SNPs.
The investigators propose that there are other SNPs in the one-carbon metabolism pathway that alter risk of ocular changes and potential vision impairment during long-duration spaceflight. To that end, extended studies of one-carbon genetics in astronauts have recently been initiated. The investigators hypothesize that the differences between genetic, biochemical, and ophthalmologic findings in PCOS and/or IIH patients and controls will mirror many of the differences found between astronauts who had ophthalmic issues during and after flight.
SPECIFIC AIMS
The key aims of this study are to: a) determine extensive one carbon pathway and related biochemistry, targeted metabolomics, and genetics (523 SNPs of the 85 major genes), and b) conduct ophthalmologic exams on patients in one of four treatment groups:
- women diagnosed with PCOS without IIH
- women diagnosed with PCOS and IIH
- women diagnosed with IIH without PCOS
- women without PCOS or IIH Participants will be matched by age and body mass index (BMI). Statistical analyses will be used to evaluate the independent and shared contributions of age, body mass (BMI), and genetics on biochemical, and ophthalmologic outcomes, with False Discovery Rate adjustments to account for multiple comparisons.
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
- 18 Years 至 50 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- •Clinical diagnosis of PCOS and/or IIH
- •No current medications for the treatment of PCOS
- •Age and BMI-matched healthy women without PCOS or IIH will be used as controls
排除标准
- •Clinical diagnosis of Cushing's syndrome
- •Untreated hypo/hyperthyroidism, elevated prolactin, congenital adrenal hyperplasia, renal insufficiency or diabetes.
- •Currently taking medications that can affect androgen concentrations or insulin sensitivity.
- •Pregnant, breast-feeding, taking oral contraceptives or currently smoking.
- •Taking medications that affect folate or B12 metabolism, such as methotrexate, trimethoprim, triamterene, phenobarbital, phenytoin, carbamazepine, gabapentin, or primidone or topiramate.
结局指标
主要结局
Ophthalmologic exam - US
时间窗: 1 Day
Eye ultrasound exam
Single Nucleotide Polymorphism (SNP) Genetic Testing related to 1-Carbon Metabolism Pathway for 523 SNPs
时间窗: 1 Day
Ophthalmologic exam -Fundus
时间窗: 1 Day
Fundus photography
Ophthalmologic exam -Vision
时间窗: 1 Day
Cycloplegic refraction test
Ophthalmologic exam -IOP
时间窗: 1 Day
Intraocular pressure
Ophthalmologic exam -OCT
时间窗: 1 Day
Optical coherence tomography test
次要结局
- Questionnaire(1 Day)
- B-vitamin Status - serum B12(1 Day)
- Hemoglobin(1 Day)
- Homocysteine(1 Day)
- Plasminogen Activator Inhibitor Antigen(1 Day)
- Insulin(1 Day)
- B-vitamin Status - B12(1 Day)
- Testosterone(1 Day)
- B-vitamin Status - folate(1 Day)
研究者
Scott M. Smith
Nutritionist, Manager for Nutritional Biochemistry
National Aeronautics and Space Administration (NASA)