Polycystic Ovarian SyndromePCOSNCT02896452
Astronaut Vision Issues in a Ground Analog Population: Polycystic Ovary Syndrome
An observational study of Polycystic Ovarian Syndrome and Idiopathic Intracranial Hypertension, run by National Aeronautics and Space Administration at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 50 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Polycystic Ovarian Syndrome, Idiopathic Intracranial Hypertension
- How many people
- 60 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Oct 2016to Sep 2026
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 50 years
- Women only
- Healthy volunteers accepted
- Adult
Study population: Premenopausal women, age 18-50 years.
Who may be able to join
- 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
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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.
Read the 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:
- 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.
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.
- Medical subject headings
- Polycystic Ovary Syndrome, Pseudotumor Cerebri
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| 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 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Single Nucleotide Polymorphism (SNP) Genetic Testing related to 1-Carbon Metabolism Pathway for 523 SNPs
Measured: 1 Day
Ophthalmologic exam -OCT
Optical coherence tomography test
Measured: 1 Day
Ophthalmologic exam -Fundus
Fundus photography
Measured: 1 Day
Ophthalmologic exam - US
Eye ultrasound exam
Measured: 1 Day
Ophthalmologic exam -Vision
Cycloplegic refraction test
Measured: 1 Day
Ophthalmologic exam -IOP
Intraocular pressure
Measured: 1 Day
Secondary outcomes (9)
Questionnaire
Questions related to birthplace, as well as birthplace of parents and grandparents, if known
Measured: 1 Day
B-vitamin Status - folate
Serum Folate measurement
Measured: 1 Day
B-vitamin Status - B12
Methylmalonic acid
Measured: 1 Day
B-vitamin Status - serum B12
Serum vitamin B-12
Measured: 1 Day
Testosterone
Measured: 1 Day
Hemoglobin
Measured: 1 Day
Plasminogen Activator Inhibitor Antigen
Measured: 1 Day
Insulin
Measured: 1 Day
Homocysteine
Measured: 1 Day
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Sep 2016 (estimated)
- Study start1 Oct 2016
- Primary completionMar 2020
- Study completionSep 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Polycystic Ovarian SyndromeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 60 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Aeronautics and Space Administration
- Collaborators
- University of Texas, Mayo Clinic, University of Florida, University of North Carolina, Coastal Eye Associates
- Responsible party
- Principal investigator, Scott M. Smith, National Aeronautics and Space Administration (NASA)
- Investigators
- Scott M Smith, PhD, Principal investigator, National Aeronautics and Space Administration (NASA)Alice Y Chang, MD, Principal investigator, Mayo Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02896452
- Sponsor's protocol ID
- NASA
- Acronym
- PCOS
- Status last verified
- May 2025
- First submitted
- 24 Aug 2016
- Last updated
- 22 May 2025
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Yes: Data will be provided upon subject request.
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.
PubMed 26316272Zwart 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.
PubMed 22298570
Study at a glance
From the registry record, last updated by the sponsor on 22 May 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Astronaut Vision Issues and One Carbon Metabolism: Expanded Polymorphism Evaluation and Evaluation in a Potential Analog Population
- ClinicalTrials.gov ID
- NCT02896452
- Acronym / sponsor ID
- PCOS / NASA
- Study type
- Observational
- Recruitment status
- Active, not recruiting
- Enrolment
- 60 participants (actual)
- Lead sponsor
- National Aeronautics and Space Administration
- Collaborators
- University of Texas, Mayo Clinic, University of Florida, University of North Carolina, Coastal Eye Associates
- Study start
- 1 Oct 2016 (actual)
- Primary completion
- Mar 2020 (actual)
- Study completion
- Sep 2026 (estimated)
- First posted
- 12 Sep 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- 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.
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
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| 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 |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
- Study population
- Premenopausal women, age 18-50 years.
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (5 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
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
9 secondary outcomes
Questionnaire
Time frame: 1 Day
B-vitamin Status - folate
Time frame: 1 Day
B-vitamin Status - B12
Time frame: 1 Day
B-vitamin Status - serum B12
Time frame: 1 Day
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
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 May 2025.
- Background: PubMed 26316272Zwart 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.
- Background: PubMed 22298570Zwart 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.
- Individual participant dataSharing planned: Yes. Data will be provided upon subject request.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Scott M Smith, PhD principal investigator
National Aeronautics and Space Administration (NASA)
Alice Y Chang, MD principal investigator
Mayo Clinic
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Polycystic Ovarian Syndrome and Idiopathic Intracranial Hypertension, run by National Aeronautics and Space Administration at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 22 May 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Single Nucleotide Polymorphism (SNP) Genetic Testing related to 1-Carbon Metabolism Pathway for 523 SNPs (time frame: 1 Day). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02896452, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 May 2025.