Role of Endothelial Function in SCI CVD Risk

NCT06443151 | Recruiting

• 1 other identifier: 2016729-2
• Study Type: observational
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

Individuals with spinal cord injury have heart attacks and strokes more frequently, and much earlier in life. People with spinal cord injuries develop plaque in vessels much faster, and the reasons why are unclear. Doctors generally attributed the increased risk with weight gain and developing diabetes, but many studies have shown that even without these common factors, plaque in vessels is developing more often and faster. Endothelial cells are a single layer of cells that line all vessels in the body and plays an important role in vessel health. Damage to endothelial cells is known to lead to heart attacks and strokes. Past studies on endothelial cells of people with spinal cord injury have been unclear. The investigators have new data that these cells are unhealthy after spinal cord injury a measurement. This includes measuring endothelial health by directly altering its function using a catheter in the arm and measuring small particles in blood called endothelial microvesicles. If the project is successful, the investigators will learn important information on the health of endothelial cells after spinal cord injury. The investigators will also be able to use these markers of endothelial cell function to create treatments to improve vessel health and prevent heart attacks and strokes later in life in people with spinal cord injury.

Conditions

Spinal Cord Injuries; Cardiovascular Diseases; Endothelial Dysfunction

Outcome Measures

Primary Outcomes (6)

• Endothelium-dependent vasodilation

  Total forearm blood flow with be measured by strain gauge venous plethysmography under baseline conditions and under pharmacological manipulation with acetylcholine at increasing concentrations (8, 16, 32ug/ml).

  Measured at baseline (without acetylcholine) and immediately after each acetylcholine 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

• Association of Endothelial cell-derived microvesicles to Endothelium-dependent vasodilation

  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

Men and women of all races, ethnic backgrounds, over the age of 18 years: adults with chronic (\>12 months), motor complete (AIS A/B) SCI with paraplegia (neurological level of injury \[NLI\] at T2 or below).

Procedure: Brachial intra-arterial infusion of vasoactive and antioxidant drugs (acetylcholine, nitroprusside, ascorbic acid); Procedure: venous occlusion plethysmography; Drug: Acetylcholine; Drug: Sodium Nitroprusside; Drug: Ascorbic acid; Procedure: venous phlebotomy

Control (Non-Spinal Cord Injury)

Non-injured men and women of all races, ethnic backgrounds, over the age of 18 years.

Procedure: Brachial intra-arterial infusion of vasoactive and antioxidant drugs (acetylcholine, nitroprusside, ascorbic acid); Procedure: venous occlusion plethysmography; Drug: Acetylcholine; Drug: Sodium Nitroprusside; Drug: Ascorbic acid; Procedure: venous phlebotomy

Interventions

Brachial intra-arterial infusion of vasoactive and antioxidant drugs (acetylcholine, nitroprusside, ascorbic acid) PROCEDURE

The brachial artery in the non-dominant arm will be catheterized to infuse endothelium-dependent vasodilator acetylcholine, endothelium-independent vasodilator nitroprusside, and antioxidant ascorbic acid at concentrations to have isolated effect in the forearm.

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

venous occlusion plethysmography PROCEDURE

Whole forearm blood flow will be measured by mercury-strain gauge while venous occlusion is applied to the forearm and hand by rapid-cuff inflation to sub-arterial pressures. Changes in whole forearm blood flow with be measured at baseline, endothelial agonists, and removal of oxidative stress via acorbic acid.

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

Acetylcholine DRUG

Endothelium-dependent vasodilation will then be assessed by changes in FBF in response to intra-arterial infusions of the endothelial agonist acetylcholine infused at rates of 4.0, 8.0, 16.0 μg/100 mL of forearm tissue/min to generate a dose-response curve.

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

Sodium Nitroprusside DRUG

Endothelium-independent vasodilation will be assessed by changes in forearm blood flow in response to intra-arterial infusions of sodium nitroprusside at 1.0, 2.0, 4.0 μg/100 mL forearm tissue/min.

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

Ascorbic acid DRUG

Ascorbic acid will be infused at a constant rate (12 mg/100 mL tissue/min) and maintained at the same rate while the acetylcholine and sodium nitroprusside dose-response curves are repeated.

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

venous phlebotomy PROCEDURE

Venous blood samples will be collected to measure baseline cardiometabolic characteristics and isolate endothelial cell microvesicles for characterizations and in vitro experiments.

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

Eligibility Criteria

• Age: 18 Years - 89 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Men and women of all races, ethnic backgrounds, over the age of 18 years with history chronic motor complete paraplegia, but free of overt chronic diseases assessed by clinically documented medical history, physical examination, and blood chemistries and hematological evaluation.

You may qualify if:

• Men and women of all races, ethnic backgrounds\>18 years of age
• Traumatic spinal cord injury (Sports, Assault, Transport, Fall, Other Traumatic Causes)
• Time since injury (\> 12 months)
• Paraplegia Motor Complete Injury (neurological level of injury at T2 or below, ASIA Impairment Scale A or B

You may not qualify if:

• History of high blood pressure
• History cardiovascular disease (coronary artery disease, congestive heart failure, myocardial infarction, cerebrovascular accident).
• History high cholesterol
• History of Diabetes Type I or Type II
• History of Obstructive Pulmonary Disease
• History of Chronic Kidney or Liver Disease
• History of Cancer
• History of Autoimmune Disease (Thyroid Disease, Lupus, Rheumatoid Arthritis, etc).
• History of smoking tobacco in the last 12 months
• History of alcohol use

Sponsors & Collaborators

• Craig Hospital: lead
• University of Colorado, Boulder: collaborator

Study Sites (1)

Craig Hospital

Englewood, Colorado, 80113, United States

RECRUITING

Related Links

• Related Info

MeSH Terms

Conditions

Spinal Cord Injuries; Cardiovascular Diseases

Interventions

Acetylcholine; Nitroprusside; Ascorbic Acid

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Biogenic Amines; Amines; Organic Chemicals; Ferricyanides; Cyanides; Anions; Ions; Electrolytes; Inorganic Chemicals; Ferric Compounds; Iron Compounds; Hydrogen Cyanide; Nitrogen Compounds; Sugar Acids; Acids, Acyclic; Carboxylic Acids; Hydroxy Acids; Carbohydrates

Study Officials

• Andrew Park, MD

  Craig Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Clare Morey, SLP-CCC

CONTACT

303-789-8621; cmorey@craighospital.org

Andrew Park, MD

CONTACT

303-789-8101; apark@craighospital.org

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 7, 2024
• First Posted: June 5, 2024
• Study Start: September 1, 2024
• Primary Completion (Estimated): March 30, 2027
• Study Completion (Estimated): March 30, 2027
• Last Updated: August 20, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will share

Locations

US (1)