[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"trial:NCT07227740":3,"trial-entities:NCT07227740":138,"trial-summary:NCT07227740":145},{"id":4,"nct_id":4,"org_study_id":5,"brief_title":6,"official_title":7,"overall_status":8,"completion_date":9,"status_verified_date":10,"last_update_date":11,"start_date":12,"sponsor_name":13,"lead_sponsor_class":14,"has_dmc":15,"brief_summary":16,"detailed_description":17,"conditions":18,"keywords":22,"study_type":30,"primary_purpose":31,"phases":32,"enrollment_info":33,"interventions":36,"primary_outcomes":52,"secondary_outcomes":75,"sex":76,"minimum_age":77,"maximum_age":78,"healthy_volunteers":15,"eligibility_criteria":79,"std_ages":97,"locations":100,"central_contacts":130,"overall_officials":134,"references":136,"see_also_links":137},"NCT07227740","2301643","Testosterone Deficiency and Endothelial Dysfunction After Spinal Cord Injury","Testosterone Deficiency and Endothelial Dysfunction in Spinal Cord Injury Related Cardiovascular Disease Mechanistic Insights and Therapeutic Prospects","RECRUITING","2028-07-14","2025-11","2025-11-21","2025-07-15","Craig Hospital","OTHER",false,"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.","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.\n\nEndothelium-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.\n\nLow 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.\n\nThis cross-sectional study will include 48 adults with subacute (\\\u003C6 months), motor-complete (AIS A\u002FB) 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.",[19,20,21],"Spinal Cord Injuries","Endothelial Dysfunction","Testosterone Deficiency",[23,24,25,26,27,28,29],"spinal cord injury","endothelial dysfunction","testosterone deficiency","extracellular vesicles","microvesicles","vasodilation","fibrinolysis","OBSERVATIONAL",null,[],{"count":34,"type":35},48,"ESTIMATED",[37,44,48],{"type":38,"name":39,"description":40,"armGroupLabels":41},"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.",[42,43],"Adult Male with Subacute Traumatic Spinal Cord Injury with Low Testosterone","Adult Male with Subacute Traumatic Spinal Cord Injury with Normal Testosterone",{"type":38,"name":45,"description":46,"armGroupLabels":47},"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.",[42,43],{"type":38,"name":49,"description":50,"armGroupLabels":51},"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.",[42,43],[53,57,61,65,69,72],{"measure":54,"description":55,"timeFrame":56},"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\u002Fml).","Measured at baseline (without acetylcholine) and immediately after each acetylcholine dose for 3-5 minutes.",{"measure":58,"description":59,"timeFrame":60},"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\u002Fml).","Measured at baseline (without sodium nitroprusside) and immediately after each sodium nitroprusside dose for 3-5 minutes.",{"measure":62,"description":63,"timeFrame":64},"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.",{"measure":66,"description":67,"timeFrame":68},"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",{"measure":70,"description":71,"timeFrame":68},"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\u002Fnitrite parameter assays",{"measure":73,"description":74,"timeFrame":68},"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.",[],"MALE","18 Years","89 Years",{"inclusion":80,"exclusion":86,"raw_text":96},[81,82,83,84,85],"Between ages 18-89 years of age","Male Sex","History of motor complete (AIS A\u002FB) paraplegia (NLI T3 or Below)","Time since injury \\\u003C6 months at time of enrollment (Subacute injury)","Testosterone Deficiency defined as \\\u003C 300ng\u002FdL",[87,88,89,90,91,92,93,94,95],"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 (\\\u003C1 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.","Inclusion Criteria:\n\n* Between ages 18-89 years of age\n* Male Sex\n* History of motor complete (AIS A\u002FB) paraplegia (NLI T3 or Below)\n* Time since injury \\\u003C6 months at time of enrollment (Subacute injury)\n* Testosterone Deficiency defined as \\\u003C 300ng\u002FdL\n\nExclusion Criteria:\n\n* Overt cardiovascular disease assessed by a) medical history, b) physical examination c) electrocardiogram\n* Anaphylaxis to betadine, lidocaine, iodine\n* Active infection at time of enrollment.\n* Recent surgery (\\\u003C1 month) at time of enrollment.\n* History smoking tobacco (currently or in the past 12 months)\n* History of more than low-risk history of alcohol consumption\n* History of drug abuse\n* History of use of cardiovascular-acting (i.e. statins, beta-blockers) therapeutics\n* History of other health habits, medications, and supplements that could influence the outcome measures deemed by principal investigators and investigative team.",[98,99],"ADULT","OLDER_ADULT",[101],{"facility":13,"status":8,"city":102,"state":103,"zip":104,"country":105,"contacts":106,"geoPoint":127},"Englewood","Colorado","80113","United States",[107,112,116,118,121,123,125],{"name":108,"role":109,"phone":110,"email":111},"Genevieve Madera, BS","CONTACT","7203454640","Gmadera@craighospital.org",{"name":113,"role":109,"phone":114,"email":115},"Andrew Park, MD","303-789-8101","apark@craighospital.org",{"name":113,"role":117},"PRINCIPAL_INVESTIGATOR",{"name":119,"role":120},"Christopher DeSouza, PhD","SUB_INVESTIGATOR",{"name":122,"role":120},"Brian Stauffer, MD",{"name":124,"role":120},"Josh Yarrow",{"name":126,"role":120},"Kerrie Moreau",{"lat":128,"lon":129},39.64777,-104.98776,[131,133],{"name":108,"role":109,"phone":132,"email":111},"17203454640",{"name":113,"role":109,"phone":114,"email":115},[135],{"name":113,"affiliation":13,"role":117},[],[],{"nct_id":4,"conditions":139,"biomarkers":143},[140,141,142],"Endothelial dysfunction","Spinal Cord Injury","Testosterone Deficiency, CTCAE",[144],"Testosterone",{"nct_id":4,"found":146,"summary":147,"prompt_version":157},true,{"design":148,"status":149,"heading":150,"summary":151,"follow_up":152,"word_count":153,"commitments":154,"compensation":155,"drugs_mentioned":156},"This is an observational study, meaning researchers will be observing and collecting information without giving a specific treatment. It plans to include 48 male participants.","completed","Testosterone Deficiency and Blood Vessel Health After Spinal Cord Injury","This study is looking into why people with spinal cord injuries (SCI) might have a higher and earlier risk of heart attacks and strokes. Researchers are studying how the cells lining your blood vessels, called endothelial cells, work after SCI. They will infuse small doses of medications like acetylcholine, isoproterenol, and sodium nitroprusside into your arm artery to measure blood flow. They will also infuse Vitamin C to see if it helps. About 50 mL of blood will be drawn to check for signs of blood vessel health and inflammation. This study aims to understand if low testosterone contributes to problems with blood vessels after SCI. To join, you must be a male between 18-89 years old with a motor complete spinal cord injury (paraplegia) that happened less than 6 months ago, and have low testosterone levels (below 300ng\u002FdL). The study will look at how well your blood vessels widen and how your body breaks down blood clots.","Blood vessel function and clot-breaking ability will be measured at baseline and immediately after each medication dose for 3-5 minutes.",158,"You will have a catheter placed in your arm artery for infusions of various medications and Vitamin C. Blood flow will be measured, and about 50 mL of blood will be drawn from your arm.","Not stated in the trial record.",[],"v2"]