PCOS: Astronaut Vision Issues in a Ground Analog Population: Polycystic Ovary Syndrome

Sponsor
National Aeronautics and Space Administration (NASA) (U.S. Fed)
Overall Status
Active, not recruiting
CT.gov ID
NCT02896452
Collaborator
University of Texas (Other), Mayo Clinic (Other), University of Florida (Other), University of North Carolina (Other), Coastal Eye Associates (Other)
60
1
71
0.8

Study Details

Study Description

Brief Summary

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.

Condition or Disease Intervention/Treatment Phase

    Detailed Description

    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.

    Study Design

    Study Type:
    Observational
    Actual Enrollment :
    60 participants
    Observational Model:
    Cohort
    Time Perspective:
    Prospective
    Official Title:
    Astronaut Vision Issues and One Carbon Metabolism: Expanded Polymorphism Evaluation and Evaluation in a Potential Analog Population
    Actual Study Start Date :
    Oct 1, 2016
    Actual Primary Completion Date :
    Mar 1, 2020
    Anticipated Study Completion Date :
    Sep 1, 2022

    Arms and Interventions

    Arm Intervention/Treatment
    Women diagnosed with PCOS without IIH

    Women diagnosed with polycystic ovary syndrome without idiopathic intracranial hypertension

    Women diagnosed with PCOS and IIH

    Women diagnosed with polycystic ovary syndrome and idiopathic intracranial hypertension

    Women diagnosed with IIH without PCOS

    Women diagnosed with idiopathic intracranial hypertension without polycystic ovary syndrome

    Women without PCOS or IIH

    Women age and body mass index match controls without polycystic ovary syndrome or intracranial hypertension

    Outcome Measures

    Primary Outcome Measures

    1. Single Nucleotide Polymorphism (SNP) Genetic Testing related to 1-Carbon Metabolism Pathway for 523 SNPs [1 Day]

    2. Ophthalmologic exam -OCT [1 Day]

      Optical coherence tomography test

    3. Ophthalmologic exam -Fundus [1 Day]

      Fundus photography

    4. Ophthalmologic exam - US [1 Day]

      Eye ultrasound exam

    5. Ophthalmologic exam -Vision [1 Day]

      Cycloplegic refraction test

    6. Ophthalmologic exam -IOP [1 Day]

      Intraocular pressure

    Secondary Outcome Measures

    1. Questionnaire [1 Day]

      Questions related to birthplace, as well as birthplace of parents and grandparents, if known

    2. B-vitamin Status - folate [1 Day]

      Serum Folate measurement

    3. B-vitamin Status - B12 [1 Day]

      Methylmalonic acid

    4. B-vitamin Status - serum B12 [1 Day]

      Serum vitamin B-12

    5. Testosterone [1 Day]

    6. Hemoglobin [1 Day]

    7. Plasminogen Activator Inhibitor Antigen [1 Day]

    8. Insulin [1 Day]

    9. Homocysteine [1 Day]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 50 Years
    Sexes Eligible for Study:
    Female
    Accepts Healthy Volunteers:
    Yes
    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.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Mayo Clinic Rochester Minnesota United States 55905

    Sponsors and Collaborators

    • National Aeronautics and Space Administration (NASA)
    • University of Texas
    • Mayo Clinic
    • University of Florida
    • University of North Carolina
    • Coastal Eye Associates

    Investigators

    • Principal Investigator: Scott M Smith, PhD, National Aeronautics and Space Administration (NASA)
    • Principal Investigator: Alice Y Chang, MD, Mayo Clinic

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    Responsible Party:
    Scott M. Smith, Nutritionist, Manager for Nutritional Biochemistry, National Aeronautics and Space Administration (NASA)
    ClinicalTrials.gov Identifier:
    NCT02896452
    Other Study ID Numbers:
    • NASA
    First Posted:
    Sep 12, 2016
    Last Update Posted:
    Sep 1, 2021
    Last Verified:
    Aug 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Sep 1, 2021