Testosterone Deficiency and Endothelial Dysfunction After Spinal Cord Injury

NCT07227740 | Recruiting

• 2 other identifiers: 2301643CDMRP-SC240119
• Study Type: observational
• Target: 48
• Locations: 1 country
• Sites: 1

Brief Summary

Heart attacks and strokes are among the most common causes of premature death in individuals living with spinal cord injury (SCI) and appear to occur earlier in life. The factors that lead to the heighten and accelerated risk of heart attacks and strokes in adults living with SCI remain poorly understood. The investigators aim to uncover why this happens and find ways to prevent it. Our research focuses on how important cells which line blood vessels, called endothelial cells, function after SCI. The investigators test endothelial function in live conscious people with SCI. The investigators also study signaling molecules endothelial cells release called endothelial cell derived microvesicles (EMVs), which the investigators can measure in blood to tell us the health of endothelial cells. By using these rigorous tests of vascular function, the investigators have determined that endothelial cells appear dysfunctional after SCI. The investigators also know that many men with SCI have low testosterone levels. Our team has studied testosterone's effects on endothelial dysfunction and believe low testosterone may be contributing to endothelial dysfunction after SCI. By understanding these mechanisms, the investigators hope to improve the lives of those living with SCI and reduce their risk for heart attacks and strokes. The investigators propose to study the influence of testosterone on endothelial function by using state-of-the-art clinical and laboratory experiments to assess endothelial function in men with SCI with low and normal testosterone levels.

Conditions

Spinal Cord Injuries; Endothelial Dysfunction; Testosterone Deficiency

Keywords

spinal cord injury; endothelial dysfunction; testosterone deficiency; extracellular vesicles; microvesicles; vasodilation; fibrinolysis

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.

• Tissue plasminogen activator release

  Net endothelial release or uptake of t-PA and PAI-1 (both antigen and activity levels) at each dose of isoproterenol and sodium nitroprusside will be calculated as the product of the arteriovenous concentration gradient and the infused forearm plasma flow. Arteriovenous concentration gradients for both t-PA and PAI-1 antigen and activity for each subject (at each time point) will be determined by subtraction of the values measured in simultaneously collected venous and arterial blood samples

  Measured at baseline and immediately after each isoproterenol and 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)

Adult Male with Subacute Traumatic Spinal Cord Injury with Normal Testosterone

24 male participants of all races and ethnic backgrounds aged 18-89 years with a history of spinal cord injury and diagnosed with normal testosterone

Diagnostic Test: Intra-arterial Infusion of Vasoactive Agents; Diagnostic Test: Intra-arterial Vitamin C Infusion; Diagnostic Test: Blood Sampling

Adult Male with Subacute Traumatic Spinal Cord Injury with Low Testosterone

24 male participants of all races and ethnic backgrounds aged 18-89 years with a history of spinal cord injury and diagnosed with low testosterone

Diagnostic Test: Intra-arterial Infusion of Vasoactive Agents; Diagnostic Test: Intra-arterial Vitamin C Infusion; Diagnostic Test: Blood Sampling

Interventions

Intra-arterial Infusion of Vasoactive Agents DIAGNOSTIC_TEST

A catheter is placed in the brachial artery of the non-dominant arm, and small doses of vasoactive drugs acetylcholine, isoproterenol, sodium nitroprusside are infused. Forearm blood flow will be measured using venous occlusion plethysmography. The purpose of this procedure is to assess endothelium-dependent and independent vasodilation by stimulating different vascular pathways. The acetylcholine infusion is to test muscarinic receptor, nitro oxide dependent, endothelium-dependent vasodilation. Isoproterenol was selected to stimulate tissue plasminogen activator based on its specificity and effectiveness at eliciting local and rapid tissue plasminogen activator release in adult humans. Sodium nitroprusside infusion is to assess endothelium-independent vasodilation.

Adult Male with Subacute Traumatic Spinal Cord Injury with Low Testosterone; Adult Male with Subacute Traumatic Spinal Cord Injury with Normal Testosterone

Intra-arterial Vitamin C Infusion DIAGNOSTIC_TEST

Vitamin C, a potent antioxidant, will be infused into the forearm and forearm blood flow will be re-evaluated to determine whether oxidative stress contributes to endothelial dysfunction.

Adult Male with Subacute Traumatic Spinal Cord Injury with Low Testosterone; Adult Male with Subacute Traumatic Spinal Cord Injury with Normal Testosterone

Blood Sampling DIAGNOSTIC_TEST

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.

Adult Male with Subacute Traumatic Spinal Cord Injury with Low Testosterone; Adult Male with Subacute Traumatic Spinal Cord Injury with Normal Testosterone

Eligibility Criteria

• Age: 18 Years - 89 Years
• Gender Eligibility Details: Male sex
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Only male participants of all races and ethnic backgrounds aged 18-89 with a history of motor complete (AIS A/B) paraplegia (NLI T3 or Below). Time since injury \<6 months at time of enrollment and diagnosed with normal and low T (Testosterone Deficiency defined as \< 300ng/dL)

You may qualify if:

• Between ages 18-89 years of age
• Male Sex
• History of motor complete (AIS A/B) paraplegia (NLI T3 or Below)
• Time since injury \<6 months at time of enrollment (Subacute injury)
• Testosterone Deficiency defined as \< 300ng/dL

You may not qualify if:

• Overt cardiovascular disease assessed by a) medical history, b) physical examination c) electrocardiogram
• Anaphylaxis to betadine, lidocaine, iodine
• Active infection at time of enrollment.
• Recent surgery (\<1 month) at time of enrollment.
• History smoking tobacco (currently or in the past 12 months)
• History of more than low-risk history of alcohol consumption
• History of drug abuse
• History of use of cardiovascular-acting (i.e. statins, beta-blockers) therapeutics
• History of other health habits, medications, and supplements that could influence the outcome measures deemed by principal investigators and investigative team.

Sponsors & Collaborators

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

Interventions

Blood Specimen Collection

Condition Hierarchy (Ancestors)

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

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

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: November 11, 2025
• First Posted: November 13, 2025
• Study Start: July 15, 2025
• Primary Completion (Estimated): July 14, 2028
• Study Completion (Estimated): July 14, 2028
• Last Updated: November 21, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will share

Locations

US (1)