Astronaut Vision Issues in a Ground Analog Population: Polycystic Ovary Syndrome
| Status: | Recruiting |
|---|---|
| Conditions: | High Blood Pressure (Hypertension), Neurology, Women's Studies |
| Therapuetic Areas: | Cardiology / Vascular Diseases, Neurology, Reproductive |
| Healthy: | No |
| Age Range: | 18 - 50 |
| Updated: | 10/10/2018 |
| Start Date: | October 1, 2016 |
| End Date: | August 2020 |
| Contact: | Chelsie VanOort |
| Email: | VanOort.Chelsie@mayo.edu |
| Phone: | 507-266-3912 |
Astronaut Vision Issues and One Carbon Metabolism: Expanded Polymorphism Evaluation and Evaluation in a Potential Analog Population
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.
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.
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:
1. women diagnosed with PCOS without IIH
2. women diagnosed with PCOS and IIH
3. women diagnosed with IIH without PCOS
4. 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.
A secondary aim is to combine the patient and control data from this study with ISS
crewmember data in order to help inform us on whether or not these two cohorts (astronauts
with ophthalmic issues, PCOS patients) share similar associations among one-carbon metabolism
genetics and biochemistry and ophthalmologic data identified in the investigators' earlier
analyses.
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:
1. women diagnosed with PCOS without IIH
2. women diagnosed with PCOS and IIH
3. women diagnosed with IIH without PCOS
4. 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.
A secondary aim is to combine the patient and control data from this study with ISS
crewmember data in order to help inform us on whether or not these two cohorts (astronauts
with ophthalmic issues, PCOS patients) share similar associations among one-carbon metabolism
genetics and biochemistry and ophthalmologic data identified in the investigators' earlier
analyses.
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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.
We found this trial at
1
site
Rochester, Minnesota 55905
Principal Investigator: Alice Y Chang, MD
Phone: 507-266-3912
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