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

NCT ID: NCT02896452

Last Updated: 2025-05-22

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Total Enrollment: 60 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2016-10-01
• Study Completion Date: 2026-09-30

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.

Conditions

Polycystic Ovarian Syndrome; Idiopathic Intracranial Hypertension

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

Women diagnosed with PCOS without IIH

Women diagnosed with polycystic ovary syndrome without idiopathic intracranial hypertension

No interventions assigned to this group

Women diagnosed with PCOS and IIH

Women diagnosed with polycystic ovary syndrome and idiopathic intracranial hypertension

No interventions assigned to this group

Women diagnosed with IIH without PCOS

Women diagnosed with idiopathic intracranial hypertension without polycystic ovary syndrome

No interventions assigned to this group

Women without PCOS or IIH

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

No interventions assigned to this group

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 50 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: Yes

Sponsors

University of Texas

OTHER

Sponsor Role: collaborator

Mayo Clinic

OTHER

Sponsor Role: collaborator

University of Florida

OTHER

Sponsor Role: collaborator

University of North Carolina

OTHER

Sponsor Role: collaborator

Coastal Eye Associates

UNKNOWN

Sponsor Role: collaborator

National Aeronautics and Space Administration

UNKNOWN

Sponsor Role: lead

Responsible Party

Scott M. Smith

Nutritionist, Manager for Nutritional Biochemistry

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Scott M Smith, PhD

Role: PRINCIPAL_INVESTIGATOR

National Aeronautics and Space Administration (NASA)

Alice Y Chang, MD

Role: PRINCIPAL_INVESTIGATOR

Mayo Clinic

Locations

Mayo Clinic

Rochester, Minnesota, United States

Countries

United States

References

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.

Reference Type: BACKGROUND

PMID: 26316272 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 22298570 (View on PubMed)

Other Identifiers

NASA

Identifier Type: -

Identifier Source: org_study_id