Endothelial Dysfunction After SCI (EDASCI)

Endothelial Dysfunction After SCI: Mechanism and Therapeutic Target for SCI-related Cardiovascular Disease

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.

Study Overview

• Status: Recruiting
• Conditions: Endothelial Dysfunction; Spinal Cord Injuries
• Intervention / Treatment: Procedure: Intra-arterial Infusion of Vasoactive Agents; Procedure: Intra-arterial Vitamin C Infusion; Procedure: Blood Sampling

Detailed Description

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.

• Study Type: Observational
• Enrollment (Estimated): 40

Contacts and Locations

• Study Contact: Name: Genevieve Madera, BS; Phone Number: 17203454640; Email: Gmadera@craighospital.org
• Study Contact Backup: Name: Clare Morey, SLP-CCC; Phone Number: 303.789. 8621; Email: Gquintero@craighospital.org

Study Locations

• United States
  • Colorado
    • Englewood, Colorado, United States, 80113
      • Recruiting
      • Craig Hospital
      • Principal Investigator: Andrew Park, MD
      • Sub-Investigator: Christopher DeSouza, PhD
      • Sub-Investigator: Brian Stauffer, MD
      • Contact: Genevieve Madera, B.S.; Phone Number: 7203454640; Email: Gmadera@craighospital.org
      • Contact: Andrew Park, MD; Email: Apark@craighospital.org

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

Potential participants of this study will all be willing and eligible adults who sustained a spinal cord injury, and adults who have never sustained a spinal cord injury. Participants of all races and ethnic backgrounds will be included in this study. A total up to 40 participants will be enrolled with the goal of 20 in each group to complete the protocol.

Description

SCI Inclusion Criteria

• Over age 18 years
• Chronic (>12 months) SCI
• Motor complete (AIS A/B) SCI
• Paraplegia (neurological level of injury [NLI] at T2 or below)

Non-injured Inclusion Criteria

• Over age 18 years

Exclusion Criteria (Both SCI and Non-injured)

• Overt chronic diseases as assessed by: a) clinically documented medical history; b) physical examination; c) blood pressure and ECG at rest; and d) complete blood chemistries and hematological evaluation.
• Active infection
• Recent (< 3 months) surgery
• Current smoking history (within past 12 months)
• Report more than low-risk alcohol consumption
• History of drug abuse
• Currently taking cardiovascular (statins, beta-blockers) therapeutics and/or other medications that could influence the outcome measures

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Spinal Cord Injury; Willing and eligible adults over the age of 18 years who sustained a motor complete (AIS A/B) paraplegia (neurological level of injury at T2 or below) spinal cord injury greater than 12 months ago. Participants of all races and ethnic backgrounds will be included in this study.	Procedure: Intra-arterial Infusion of Vasoactive Agents; 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.; Procedure: Intra-arterial Vitamin C Infusion; 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.; Procedure: Blood Sampling; 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)
Control (Non-Spinal Cord Injury); Adults greater than 18 years of age who have never sustained a spinal cord injury. Participants of all races and ethnic backgrounds will be included in this study	Procedure: Intra-arterial Infusion of Vasoactive Agents; 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.; Procedure: Intra-arterial Vitamin C Infusion; 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.; Procedure: Blood Sampling; 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)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Endothelium-independent vasodilation	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).	Measured at baseline (without sodium nitroprusside) and immediately after each sodium nitroprusside dose for 3-5 minutes.
Endothelial cell-derived microvesicles concentration	Endothelial cell-derived microvesicles will be collected from venous blood samples and counted used flow cytometry to determine a circulating concentration.	Baseline
Endothelial cell-derived microvesicles effects of human coronary artery endothelial cells nitric oxide bioavailability	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.	Baseline
Endothelial cell-derived microvesicles effects of human coronary artery endothelial cells reactive oxygen species and antioxidant capacity	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.	Baseline
Endothelium-dependent vasodilation	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.	Measured at baseline and immediately after each vasoactive dose for 3-5 minutes.

Collaborators and Investigators

• Sponsor: Craig Hospital
• Collaborators: University of Colorado, Boulder; Denver Health and Hospital Authority
• Investigators: Principal Investigator: Andrew Park, MD, Craig Hospital

Study record dates

Study Major Dates

• Study Start (Actual): July 31, 2025
• Primary Completion (Estimated): July 30, 2027
• Study Completion (Estimated): July 30, 2027

Study Registration Dates

• First Submitted: November 11, 2025
• First Submitted That Met QC Criteria: November 11, 2025
• First Posted (Estimated): November 13, 2025

Study Record Updates

• Last Update Posted (Estimated): November 14, 2025
• Last Update Submitted That Met QC Criteria: November 12, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: spinal cord injury; endothelium-dependent vasodilation; extracellular vesicles; microvesicles
• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Wounds and Injuries; Trauma, Nervous System; Spinal Cord Diseases; Spinal Cord Injuries; Investigative Techniques; Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Blood Specimen Collection
• Other Study ID Numbers: 1341523 (Other Grant/Funding Number: Craig H Neilsen Foundation)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Data sharing will be facilitated through active participation in Open Data Commons for SCI (ODC-SCI). ODC-SCI is a cloud-based community-governed repository to store, share, and publish research data on Spinal Cord Injury and is compliant with requirements for FAIR and trustworthy repositories established by NIH.

Drug and device information, study documents

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