B-Complex: A Nutraceutical SANS Countermeasure

Study Overview
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Brief Summary
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In this project, the investigators propose to test effectiveness of a daily nutraceutical supplement containing bioactive B vitamins to mitigate optic disc edema in astronauts. The proposed countermeasure is intended to maximize functioning of the one-carbon metabolic pathway to provide enough substrate and cofactors to overcome any genetic differences that may impact the efficiency of enzyme function. By optimizing the pathway, this will 1) optimize endothelial function by increasing eNOS coupling and nitric oxide synthesis and 2) optimize collagen firmness and elasticity in the sclera and lamina cribrosa, and 3) minimize changes in total retinal thickness during and after flight. The protocol includes assessments of ocular health and function, along with determinants of vascular endothelial function, advanced glycation end products, and nutritional status and one carbon biochemistry. These additional measures will be critical for the further definition of the causes of optic disc edema in some astronauts after long-duration space flight, and in understanding the effect of the countermeasure. Finally, the supplemented subjects in this study will be compared against total retinal thickness data from previously flown astronauts known to have not taken supplements during their missions.

Detailed Description
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Fasting (8-h) blood samples (7.5 mL SST and 5 mL EDTA tubes, 12.5 mL total per session) will be collected approximately 180 days and 45 days before flight, on approximate flight day 90, and 30 days before landing, Return to Earth +0-2 days and 30 days after landing. Blood samples will be analyzed for vitamin status and one-carbon biochemistry, as previously described. One blood sample (collected before flight) will be analyzed for approximately 511 SNPs matching the profile of testing from our ongoing research related to optic disc edema. Serum samples will be analyzed for biochemistry measures evaluating endothelial function, vitamin status, and oxidative damage. Nutritional status assessment data, including inflight dietary intake and body mass data, completed for routine medical requirements will be requested for data sharing. Inflight medical exercise log data as well as available standard measures data will also be requested for data sharing. Medication use/Med Logs will also be requested for data sharing. Vascular function VENDYS-II (Endothelix, Inc) will be used to assess reactive hyperaemia through changes in fingertip temperature. The test consists of an automated blood pressure measurement followed by cuff occlusion of the right arm for 2 to 5 min. During this time, the fingertip temperature in the right hand decreases because of the lack of circulation in the fingertip. After the cuff is released, blood flow resumes, causing a temperature rebound in the fingertip in a manner that is proportional to vascular reactivity. Advanced Glycation End (AGE) Products Skin autofluorescence (SAF) will be analyzed non-invasively using an AGE reader (Diagnoptics Technologies, Groningen, the Netherlands). The AGE reader illuminates a skin surface of approximately 4 cm2, guarded against surrounding light, with an excitation light source with wavelength between 300 and 429 nm. This method is based on the fluorescent properties of certain AGEs accumulated in dermal tissue. OCT and OCT-A Optical coherence tomography (OCT) and OCT-angiography (OCT-A) scans will be acquired using the Spectralis OCT2 (Heidelberg Engineering) before, during, and after flight. The scan pattern includes 24 B-scans centered in a radial pattern over the optic nerve head, as well as a 3.5 mm circle scan surrounding the optic nerve head for assessment of retinal nerve fiber layer thickness and choroid thickness. For OCT-A, five consecutive volume scans will be obtained in these regions, each containing 216 A-scans. These images will be registered, and the consecutive B-scans will be used to calculate the decorrelation among the images to provide split-spectrum amplitude decorrelation angiography (SSADA) images. This decorrelation between consecutive B-scan images will be used to highlight locations where there is blood flow. The density of the perfused peripapillary vessels within the various layers of the retina will be calculated to create a flow density map.

Official Title
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B-Complex: A Nutraceutical SANS Countermeasure

Conditions
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Optic Disc Edema, Endothelial Dysfunction

Intervention / Treatment
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* Drug: Vitamin B-Complex Supplement


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: • Must be astronauts selected for 6-12 month missions on the International Space Station Exclusion Criteria: • Subjects taking B-vitamin supplements
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Supplemented with B-Complex<br>Subjects will take a vitamin B-complex supplement before, during, and after a 6-12 month spaceflight on the International Space Station | Drug: Vitamin B-Complex Supplement<br>* Vitamin B-Complex Supplement containing: 5-methyltetrahydrofolate, riboflavin 5 phosphate, pyridoxal phosphate, and methylcobalamin<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Optic Disc Edema | Measure change in total retinal thickness during and after flight compared to preflight using OCT | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Endothelial function | Assess reactive hyperemia through changes in fingertip temperature | 6 months | 
| Advanced Glycation End Products (AGE) | Skin autofluorescence (SAF) will be analyzed non-invasively using an AGE reader | 6 months | 
| Serum folate status | Vitamin status assessed from a fasting blood sample | 6 months | 
| Red Blood Cell folate status | Vitamin status assessed from a fasting blood sample | 6 months | 
| Vitamin B6 status | Vitamin status assessed from a fasting blood sample | 6 months | 
| Vitamin B12 status | Vitamin status assessed from a fasting blood sample | 6 months | 
| Glucose | Serum glucose from a fasting blood sample | 6 months | 
| Nitric oxide | Serum nitric oxide from a fasting blood sample | 6 months | 
| tetrahydrobiopterin | Serum biochemistry from a fasting blood sample | 6 months | 
| Dihydrobiopterin | Serum biochemistry from a fasting blood sample | 6 months | 
| Oxidized glutathione | Serum biochemistry from a fasting blood sample | 6 months | 
| Total antioxidant capacity | Serum biochemistry from a fasting blood sample | 6 months | 
| Advanced glycation end products | Serum biochemistry from a fasting blood sample | 6 months | 
| Albumin | Serum biochemistry from a fasting blood sample | 6 months | 
| Glycated albumin | Serum biochemistry from a fasting blood sample | 6 months | 
| 3-nitrotyrosine | Serum biochemistry from a fasting blood sample | 6 months | 
| Formate | Serum biochemistry from a fasting blood sample | 6 months | 
| MMP-2 | Serum biochemistry from a fasting blood sample | 6 months | 
| MMP-9 | Serum biochemistry from a fasting blood sample | 6 months | 
| TIMP-1 | Serum biochemistry from a fasting blood sample | 6 months | 
| TIMP-2 | Serum biochemistry from a fasting blood sample | 6 months | 
| Heparan sulfate | Serum biochemistry from a fasting blood sample | 6 months | 
| Syndecan-1 | Serum biochemistry from a fasting blood sample | 6 months | 
| Glypican | Serum biochemistry from a fasting blood sample | 6 months | 
| Hyaluronan | Serum biochemistry from a fasting blood sample | 6 months | 
| Total lipid peroxides | Serum biochemistry from a fasting blood sample | 6 months |