Testosterone Deficiency and Endothelial Dysfunction After Spinal Cord Injury
Trial statusRecruiting
Trial phaseNot listed
Trial typeObservational
Biological sexMale
Age18-89
SponsorCraig Hospital
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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)
Disqualifiers
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.
Trial 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)
Trial design
Design model
Case-control
Time perspective
Cross-sectional
Treatments tested in this trial
Intra-arterial Infusion of Vasoactive Agents
Diagnostic testA 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.
Intra-arterial Vitamin C Infusion
Diagnostic testVitamin 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.
Blood Sampling
Diagnostic testBlood 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.
Treatment groups
48 Participants
are divided into 2 treatment groupsGroup A: Adult Male with Subacute Traumatic Spinal Cord Injury with Normal Testosterone3 interventions
Group B: Adult Male with Subacute Traumatic Spinal Cord Injury with Low Testosterone3 interventions
Trial outcomes
Primary outcomes
1
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).
Time frame
Measured at baseline (without acetylcholine) and immediately after each acetylcholine dose for 3-5 minutes.2
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).
Time frame
Measured at baseline (without sodium nitroprusside) and immediately after each sodium nitroprusside dose for 3-5 minutes.3
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
Time frame
Measured at baseline and immediately after each isoproterenol and sodium nitroprusside dose for 3-5 minutes.4
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.
Time frame
BaselineSponsors and contacts
Click on the lead sponsor to view all of their trials.
Craig Hospital
Lead sponsor
University of Colorado, Boulder
Collaborator
Denver Health and Hospital Authority
Collaborator
University of Colorado, Denver
Collaborator
Source ClinicalTrials.gov