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

• ClinicalTrials.gov Identifier: NCT02896452
• Recruitment Status: Active, not recruiting
• First Posted: September 12, 2016
• Last Update Posted: September 27, 2022
• Sponsor: National Aeronautics and Space Administration (NASA)
• Collaborators: University of Texas; Mayo Clinic; University of Florida; University of North Carolina; Coastal Eye Associates
• Information provided by (Responsible Party): Scott M. Smith, National Aeronautics and Space Administration (NASA)

Tracking Information

• First Submitted Date: August 24, 2016
• First Posted Date: September 12, 2016
• Last Update Posted Date: September 27, 2022
• Actual Study Start Date: October 1, 2016
• Actual Primary Completion Date: March 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 9, 2016)

• Single Nucleotide Polymorphism (SNP) Genetic Testing related to 1-Carbon Metabolism Pathway for 523 SNPs [ Time Frame: 1 Day ]
• Ophthalmologic exam -OCT [ Time Frame: 1 Day ]
  Optical coherence tomography test
• Ophthalmologic exam -Fundus [ Time Frame: 1 Day ]
  Fundus photography
• Ophthalmologic exam - US [ Time Frame: 1 Day ]
  Eye ultrasound exam
• Ophthalmologic exam -Vision [ Time Frame: 1 Day ]
  Cycloplegic refraction test
• Ophthalmologic exam -IOP [ Time Frame: 1 Day ]
  Intraocular pressure

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: September 9, 2016)

• Questionnaire [ Time Frame: 1 Day ]
  Questions related to birthplace, as well as birthplace of parents and grandparents, if known
• B-vitamin Status - folate [ Time Frame: 1 Day ]
  Serum Folate measurement
• B-vitamin Status - B12 [ Time Frame: 1 Day ]
  Methylmalonic acid
• B-vitamin Status - serum B12 [ Time Frame: 1 Day ]
  Serum vitamin B-12
• Testosterone [ Time Frame: 1 Day ]
• Hemoglobin [ Time Frame: 1 Day ]
• Plasminogen Activator Inhibitor Antigen [ Time Frame: 1 Day ]
• Insulin [ Time Frame: 1 Day ]
• Homocysteine [ Time Frame: 1 Day ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Astronaut Vision Issues in a Ground Analog Population: Polycystic Ovary Syndrome
• Official Title: Astronaut Vision Issues and One Carbon Metabolism: Expanded Polymorphism Evaluation and Evaluation in a Potential Analog Population
• 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.

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 Type: Observational
• Study Design: Observational Model: Cohort; Time Perspective: Prospective
• Target Follow-Up Duration: Not Provided

Biospecimen

Retention:   Samples Without DNA

Description:

The Mayo Clinic/NASA would like to keep the samples for future research. The subjects can still take part in the current study even if they don't want their sample to be used for future research. If the subject agrees to give their sample it will become the property of NASA. Some future studies may examine the DNA. The PI would contact the subject if there are findings which would be useful for the subjects' health care. The subject would be given general information on the potential risks, benefits, and costs of choosing to learn about the findings.

• Sampling Method: Non-Probability Sample
• Study Population: Premenopausal women, age 18-50 years.

Condition

• Polycystic Ovarian Syndrome
• Idiopathic Intracranial Hypertension

• Intervention: Not Provided

Study Groups/Cohorts

• 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

Publications *

• Zwart SR, Gregory JF, Zeisel SH, Gibson CR, Mader TH, Kinchen JM, Ueland PM, Ploutz-Snyder R, Heer MA, Smith SM. Genotype, B-vitamin status, and androgens affect spaceflight-induced ophthalmic changes. FASEB J. 2016 Jan;30(1):141-8. doi: 10.1096/fj.15-278457. Epub 2015 Aug 27.
• Zwart SR, Gibson CR, Mader TH, Ericson K, Ploutz-Snyder R, Heer M, Smith SM. Vision changes after spaceflight are related to alterations in folate- and vitamin B-12-dependent one-carbon metabolism. J Nutr. 2012 Mar;142(3):427-31. doi: 10.3945/jn.111.154245. Epub 2012 Feb 1.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: May 28, 2020): 60
• Original Estimated Enrollment (submitted: September 9, 2016): 80
• Estimated Study Completion Date: September 2023
• Actual Primary Completion Date: March 2020 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: Female

• Ages: 18 Years to 50 Years (Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT02896452
• Other Study ID Numbers: NASA
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: Data will be provided upon subject request.

• Current Responsible Party: Scott M. Smith, National Aeronautics and Space Administration (NASA)
• Original Responsible Party: Same as current
• Current Study Sponsor: National Aeronautics and Space Administration (NASA)
• Original Study Sponsor: Same as current

Collaborators

• 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

• PRS Account: National Aeronautics and Space Administration (NASA)
• Verification Date: September 2022