Testosterone Deficiency and Endothelial Dysfunction After Spinal Cord Injury

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

Interventions

DIAGNOSTIC_TEST

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, 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.

DIAGNOSTIC_TEST

Intra-arterial Vitamin C Infusion

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.

DIAGNOSTIC_TEST

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.

Sponsors & Collaborators

• University of Colorado, Boulder

  collaborator OTHER

• Denver Health and Hospital Authority

  collaborator OTHER

• University of Colorado, Denver

  collaborator OTHER

• Craig Hospital

  lead OTHER

Principal Investigators

• Andrew Park, MD · Craig Hospital

Eligibility

Min Age

18 Years

Max Age

89 Years

Sex

MALE

Healthy Volunteers

No

Timeline & Regulatory

Start

2025-07-15

Primary Completion

2028-07-14

Completion

2028-07-14

Countries

• United States

Study Locations