Endothelial Dysfunction After SCI

NCT07227727 | Recruiting

• 1 other identifier: 1341523
• Study Type: observational
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Spinal Cord Injuries; Endothelial Dysfunction

Keywords

spinal cord injury; endothelium-dependent vasodilation; extracellular vesicles; microvesicles

Outcome Measures

Primary Outcomes (5)

• 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.

• 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

Study Arms (2)

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; Procedure: Intra-arterial Vitamin C Infusion; Procedure: Blood Sampling

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; Procedure: Intra-arterial Vitamin C Infusion; Procedure: Blood Sampling

Interventions

Intra-arterial Infusion of Vasoactive Agents PROCEDURE

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.

Control (Non-Spinal Cord Injury); Spinal Cord Injury

Intra-arterial Vitamin C Infusion PROCEDURE

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.

Control (Non-Spinal Cord Injury); Spinal Cord Injury

Blood Sampling PROCEDURE

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); Spinal Cord Injury

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• Craig Hospital: lead
• University of Colorado, Boulder: collaborator
• Denver Health and Hospital Authority: collaborator

Study Sites (1)

Craig Hospital

Englewood, Colorado, 80113, United States

RECRUITING

Biospecimen

Retention: SAMPLES WITHOUT DNA

Serum, Plasma

MeSH Terms

Conditions

Spinal Cord Injuries

Interventions

Blood Specimen Collection

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Trauma, Nervous System; Wounds and Injuries

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Andrew Park, MD

  Craig Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Genevieve Madera, BS

CONTACT

17203454640; Gmadera@craighospital.org

Clare Morey, SLP-CCC

CONTACT

303.789. 8621; Gquintero@craighospital.org

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Physician Researcher at Craig Hospital

Study Record Dates

• First Submitted: November 11, 2025
• First Posted: November 13, 2025
• Study Start: July 31, 2025
• Primary Completion (Estimated): July 30, 2027
• Study Completion (Estimated): July 30, 2027
• Last Updated: November 14, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will share

Locations

US (1)