B-Complex: A Nutraceutical SANS Countermeasure

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.

Study Overview

• Status: Recruiting
• Conditions: Endothelial Dysfunction; Optic Disc Edema
• Intervention / Treatment: Drug: Vitamin B-Complex Supplement

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 16
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Sara Zwart, PhD; Phone Number: 2814833753; Email: sara.zwart-1@nasa.gov
• Study Contact Backup: Name: Eden Fields; Phone Number: 2814837864; Email: eden.e.fields@nasa.gov

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77058
      • Recruiting
      • Johnson Space Center
      • Contact: Eden Fields

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Must be astronauts selected for 6-12 month missions on the International Space Station

Exclusion Criteria:

• Subjects taking B-vitamin supplements

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Supplemented with B-Complex; 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; Vitamin B-Complex Supplement containing: 5-methyltetrahydrofolate, riboflavin 5 phosphate, pyridoxal phosphate, and methylcobalamin

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: National Aeronautics and Space Administration (NASA)
• Collaborators: Mayo Clinic; Texas A&M University
• Investigators: Principal Investigator: Sara R Zwart, PhD, UTMB

Publications and helpful links

General Publications

• Zwart SR, Laurie SS, Chen JJ, Macias BR, Lee SMC, Stenger M, Grantham B, Carey K, Young M, Smith SM. Association of Genetics and B Vitamin Status With the Magnitude of Optic Disc Edema During 30-Day Strict Head-Down Tilt Bed Rest. JAMA Ophthalmol. 2019 Oct 1;137(10):1195-1200. doi: 10.1001/jamaophthalmol.2019.3124.
• Zwart SR, Gibson CR, Gregory JF, Mader TH, Stover PJ, Zeisel SH, Smith SM. Astronaut ophthalmic syndrome. FASEB J. 2017 Sep;31(9):3746-3756. doi: 10.1096/fj.201700294. Epub 2017 May 25.
• Smith SM, Zwart SR. Spaceflight-related ocular changes: the potential role of genetics, and the potential of B vitamins as a countermeasure. Curr Opin Clin Nutr Metab Care. 2018 Nov;21(6):481-488. doi: 10.1097/MCO.0000000000000510.
• McGregor HR, Lee JK, Mulder ER, De Dios YE, Beltran NE, Kofman IS, Bloomberg JJ, Mulavara AP, Smith SM, Zwart SR, Seidler RD. Ophthalmic changes in a spaceflight analog are associated with brain functional reorganization. Hum Brain Mapp. 2021 Sep;42(13):4281-4297. doi: 10.1002/hbm.25546. Epub 2021 Jun 9.
• Laurie SS, Vizzeri G, Taibbi G, Ferguson CR, Hu X, Lee SMC, Ploutz-Snyder R, Smith SM, Zwart SR, Stenger MB. Effects of short-term mild hypercapnia during head-down tilt on intracranial pressure and ocular structures in healthy human subjects. Physiol Rep. 2017 Jun;5(11):e13302. doi: 10.14814/phy2.13302.

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2022
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): September 30, 2032

Study Registration Dates

• First Submitted: April 29, 2022
• First Submitted That Met QC Criteria: May 5, 2022
• First Posted (Actual): May 9, 2022

Study Record Updates

• Last Update Posted (Estimated): November 8, 2023
• Last Update Submitted That Met QC Criteria: November 7, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Eye Diseases; Optic Nerve Diseases; Cranial Nerve Diseases; Papilledema; Physiological Effects of Drugs; Micronutrients; Vitamins; Hematinics; Folic Acid; Vitamin B Complex
• Other Study ID Numbers: NASA IRB STUDY00000448

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No