Testosterone Deficiency and Endothelial Dysfunction After Spinal Cord Injury
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: Intra-arterial Infusion of Vasoactive Agents, Intra-arterial Vitamin C Infusion, Blood Sampling.
- Who it may be relevant to
- Registry conditions: Spinal Cord Injuries, Endothelial Dysfunction, Testosterone Deficiency. Basic parameters: 18 years — 89 years · Male.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- United States
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
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Official title
Testosterone Deficiency and Endothelial Dysfunction in Spinal Cord Injury Related Cardiovascular Disease Mechanistic Insights and Therapeutic Prospects
Overview
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.
Detailed description
The vascular endothelium plays a central role in atherosclerotic cardiovascular disease and may contribute to the increased risk of myocardial infarction and stroke following spinal cord injury (SCI). Endothelial dysfunction is characterized by impaired vasodilator function and reduced fibrinolytic capacity.
Endothelium-dependent vasodilation is primarily mediated by nitric oxide (NO), which induces rapid relaxation of vascular smooth muscle. Fibrinolysis is the breakdown of thrombi within blood vessels, and is facilitated by endothelial cells through the synthesis and release of tissue-type plasminogen activator (t-PA). Importantly, endothelial dysfunction often precedes detectable atherosclerosis and predicts future major vascular events.
Low testosterone (T) is a common secondary complication that occurs early after SCI, with hypogonadism being four times more prevalent in men with SCI. Testosterone has known antioxidant properties and its deficiency may contribute to endothelial dysfunction. Testosterone deficiency may represent a modifiable risk factor for vascular impairment after SCI.
This cross-sectional study will include 48 adults with subacute (\<6 months), motor-complete (AIS A/B) paraplegia (neurological level T3 or below). 24 with testosterone deficiency and 24 with normal T levels. Endothelium-dependent vasodilation and t-PA capacity will be assessed via intra-arterial infusion of vasoactive drugs, with total forearm blood flow measured using venous occlusion plethysmography.
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. - 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.
Primary outcome measures
- Endothelium-dependent vasodilation [Time frame: Measured at baseline (without acetylcholine) and immediately after each acetylcholine dose for 3-5 minutes.]
- Endothelium-independent vasodilation [Time frame: Measured at baseline (without sodium nitroprusside) and immediately after each sodium nitroprusside dose for 3-5 minutes.]
- Tissue plasminogen activator release [Time frame: Measured at baseline and immediately after each isoproterenol and sodium nitroprusside dose for 3-5 minutes.]
- Endothelial cell-derived microvesicles concentration [Time frame: Baseline]
- Endothelial cell-derived microvesicles effects of human coronary artery endothelial cells nitric oxide bioavailability. [Time frame: Baseline]
- Endothelial cell-derived microvesicles effects of human coronary artery endothelial cells reactive oxygen species and antioxidant capacity [Time frame: Baseline]
Eligibility criteria
Inclusion criteria
- 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
Exclusion criteria
- 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.
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Observational model
- Case-control
Study locations
United States · 1 center
- Craig Hospital — Englewood
Identifiers
NCT: NCT07227740 · 2301643 · CDMRP-SC240119