NCT Number: NCT07227727
This study plans to learn how endothelial cells, single cell lining of blood vessels may be dysfunctional after a spinal cord injury. Endothelial dysfunction will be measured by the capacity of blood vessels to vasodilate (increase in size) and alter blood flow is lower in adults with a spinal cord injury in comparison to adults without a spinal cord injury. The mechanisms which may alter this function may be critical in reducing the risk of heart attacks and strokes in people with spinal cord injuries.
Interested in participating?
Request Info18 year and older
All sexes
Observational
Englewood, Colorado, 80113, United States
Location status: Recruiting
Andrew Park, MD
CONTACT
Andrew Park, MD
PRINCIPAL_INVESTIGATOR
Brian Stauffer, MD
SUB_INVESTIGATOR
Christopher DeSouza, PhD
SUB_INVESTIGATOR
Genevieve Madera, B.S.
CONTACT
Vascular endothelial dysfunction is prevalent after spinal cord injury (SCI) which predispose individuals with SCI to accelerated, atherosclerotic cardiovascular disease (ASCVD) and future myocardial infarctions and ischemic strokes. The central objective of this study is to determine whether adults with SCI exhibit impaired endothelial function. Specifically, if endothelium-dependent vasodilation is impaired and if endothelial cell derived microvesicles (EMVs) are elevated and dysfunctional in adults with paraplegia. Endothelium-dependent vasodilation will be assessed by pharmacologically manipulating endothelial vasodilator function in live conscious humans with SCI and determining the role of circulating EMVs as both a systemic biomarker and mediator of endothelial dysfunction.
Healthy volunteers accepted: Yes
Only the study team can determine whether someone qualifies for participation.
SCI Inclusion Criteria
Non-injured Inclusion Criteria
Exclusion criteria
(Both SCI and Non-injured)
A catheter is placed in the brachial artery of the non-dominant arm, and small doses of vasoactive drugs [acetylcholine (Ach), isoproterenol (ISO), sodium nitroprusside (SNP)] are infused. Forearm blood flow (FBF) is measured using venous occlusion plethysmography. The purpose of this procedure is to assess endothelium-dependent and independent vasodilation by stimulating different vascular pathways. The Ach infusion is to test muscarinic receptor, nitro oxide (NO) dependent, endothelium-dependent vasodilation. ISO infusion is to evaluate β-adrenergic, NO-dependent endothelium-dependent vasodilation. SNP infusion is to assess endothelium-independent vasodilation.
Vitamin C, a potent antioxidant, will be infused into the arm and forearm blood flow (FBF) will be re-evaluated to determine whether oxidative stress contributes to endothelial dysfunction.
Blood will be sampled from the antecubital vein (~50 mL) for biomarker analysis. This is to assess circulating biochemical and molecular indicators of vascular health and inflammation including levels of endothelial cell derived microvesicles (EMVs)
Time frame: Measured at baseline and immediately after each vasoactive dose for 3-5 minutes.
Total forearm blood flow with be measured by strain gauge venous plethysmography under baseline conditions and under pharmacological manipulation with acetylcholine and isoproterenol at increasing concentrations.
Time frame: Measured at baseline (without sodium nitroprusside) and immediately after each sodium nitroprusside dose for 3-5 minutes.
Total forearm blood flow with be measured by strain gauge venous plethysmography under baseline conditions and under pharmacological manipulation with sodium nitroprusside at increasing concentrations (1, 2, 4ug/ml).
Time frame: Baseline
Endothelial cell-derived microvesicles will be collected from venous blood samples and counted used flow cytometry to determine a circulating concentration.
Time frame: Baseline
Endothelial cell-derived microvesicles will be sorted and collected by fluorescence-activated cell sorting (FACS) flow cytometry. The endothelial cell-derived microvesicles will be co-cultured with human coronary artery endothelial cells. Endothelial Nitric Oxide Synthase and phosphorylation sites of interest will be measured by intracellular protein expression quantification of whole cell lysates by capillary electrophoresis immunoassays. Nitric oxide production will be assessed by total nitric oxide and nitrate/nitrite parameter assays.
Time frame: Baseline
Endothelial cell-derived microvesicles will be sorted and collected by fluorescence-activated cell sorting (FACS) flow cytometry. The endothelial cell-derived microvesicles will be co-cultured with human coronary artery endothelial cells. Super oxide dismutase and catalase expression will be measured by intracellular protein expression quantification of whole cell lysates by capillary electrophoresis immunoassays. Intracellular oxidative stress will be assessed by ROS-Glo H2O2 assay.
Contact information is provided by the study sponsor or research team.
Clare Morey, SLP-CCC
CONTACT
Genevieve Madera, BS
CONTACT
Craig Hospital
Other
Endothelial Dysfunction After SCI: Mechanism and Therapeutic Target for SCI-related Cardiovascular Disease
Acronym: EDASCI
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View the official ClinicalTrials.gov record (opens in a new tab)This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.
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