B-Complex: A Nutraceutical SANS Countermeasure

Endothelial Dysfunction Clinical Trial

Official title:

B-Complex: A Nutraceutical SANS Countermeasure

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05366933
• Other study ID #: NASA IRB STUDY00000448
• Status: Recruiting
• Phase: Phase 1
• Start date: August 1, 2022
• Est. completion date: September 30, 2032

Study information

• Verified date: May 2024
• Source: National Aeronautics and Space Administration (NASA)
• Contact: Sara Zwart, PhD
• Phone: 2814833753
• Email: sara.zwart-1[@]nasa.gov
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 16
• Est. completion date: September 30, 2032
• Est. primary completion date: July 1, 2027
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 20 Years to 100 Years

Eligibility

Inclusion Criteria:

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

Exclusion Criteria:

• Subjects taking B-vitamin supplements

Related Conditions & MeSH terms

• Endothelial Dysfunction
• Papilledema

Intervention

Drug:
• Vitamin B-Complex Supplement
Vitamin B-Complex Supplement containing: 5-methyltetrahydrofolate, riboflavin 5 phosphate, pyridoxal phosphate, and methylcobalamin

Locations

Country	Name	City	State
United States	Johnson Space Center	Houston	Texas

Sponsors (3)

Lead Sponsor	Collaborator
National Aeronautics and Space Administration (NASA)	Mayo Clinic, Texas A&M University

Country where clinical trial is conducted

United States, 

References & Publications (5)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Optic Disc Edema	Measure change in total retinal thickness during and after flight compared to preflight using OCT	6 months
Secondary	Endothelial function	Assess reactive hyperemia through changes in fingertip temperature	6 months
Secondary	Advanced Glycation End Products (AGE)	Skin autofluorescence (SAF) will be analyzed non-invasively using an AGE reader	6 months
Secondary	Serum folate status	Vitamin status assessed from a fasting blood sample	6 months
Secondary	Red Blood Cell folate status	Vitamin status assessed from a fasting blood sample	6 months
Secondary	Vitamin B6 status	Vitamin status assessed from a fasting blood sample	6 months
Secondary	Vitamin B12 status	Vitamin status assessed from a fasting blood sample	6 months
Secondary	Glucose	Serum glucose from a fasting blood sample	6 months
Secondary	Nitric oxide	Serum nitric oxide from a fasting blood sample	6 months
Secondary	tetrahydrobiopterin	Serum biochemistry from a fasting blood sample	6 months
Secondary	Dihydrobiopterin	Serum biochemistry from a fasting blood sample	6 months
Secondary	Oxidized glutathione	Serum biochemistry from a fasting blood sample	6 months
Secondary	Total antioxidant capacity	Serum biochemistry from a fasting blood sample	6 months
Secondary	Advanced glycation end products	Serum biochemistry from a fasting blood sample	6 months
Secondary	Albumin	Serum biochemistry from a fasting blood sample	6 months
Secondary	Glycated albumin	Serum biochemistry from a fasting blood sample	6 months
Secondary	3-nitrotyrosine	Serum biochemistry from a fasting blood sample	6 months
Secondary	Formate	Serum biochemistry from a fasting blood sample	6 months
Secondary	MMP-2	Serum biochemistry from a fasting blood sample	6 months
Secondary	MMP-9	Serum biochemistry from a fasting blood sample	6 months
Secondary	TIMP-1	Serum biochemistry from a fasting blood sample	6 months
Secondary	TIMP-2	Serum biochemistry from a fasting blood sample	6 months
Secondary	Heparan sulfate	Serum biochemistry from a fasting blood sample	6 months
Secondary	Syndecan-1	Serum biochemistry from a fasting blood sample	6 months
Secondary	Glypican	Serum biochemistry from a fasting blood sample	6 months
Secondary	Hyaluronan	Serum biochemistry from a fasting blood sample	6 months
Secondary	Total lipid peroxides	Serum biochemistry from a fasting blood sample	6 months