Sildenafil Treatment for Traumatic Vascular Injury in Athletes
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 22
- 试验地点
- 1
- 主要终点
- Arterial Spin Labeling
研究概览
简要总结
About 300,000 people are hospitalized for traumatic brain injury (TBI) each year. After TBI, secondary brain injury escalates due in part to heightened levels of oxidant injury, inflammation, and vascular injury. Traumatic cerebral vascular injury (TCVI) may begin almost immediately after the primary injury and evolve into chronic neurodegenerative conditions. TCVI is a very complex TBI endophenotype and microvascular injuries have been described in a plethora of animal and human TBI studies. These injuries consist of endothelial injury, disruption of the blood brain barrier (BBB), a reduction of capillary density, intravascular microthrombi, and white-matter degeneration. Recently, use of magnetic resonance imaging (MRI)-Blood Oxygen Level Dependent (BOLD) combined with hypercapnia (high spatial and temporal resolution) by our research group has proven to be more sensitive at measuring alterations of cerebral blood flow (CBF) in TBI subjects. The goal of the proposed research is to test the efficacy of Viagra® (sildenafil) at normalizing CBF and improving cognitive outcomes in people that have experienced a TBI. Sildenafil is a phosphodiesterase-5 (PDE-5) inhibitor that has previously been administered as a therapy for high blood pressure and erectile dysfunction. In people that have been affected by stroke-induce neurotrauma, sildenafil improved CBF and was found to be neuroprotective. With respect to chronic TBI, previous studies have demonstrated that sildenafil therapy potentiates cardiovascular reactivity (CVR) in areas of the brain with damaged endothelium. In this proposal, the investigators will test the hypothesis that sildenafil treatment in boxers/Mixed Martial Arts (MMA) fighters soon after concussion normalizes CBF, potentiates CVR, reduces post-concussion symptoms, and improves cognition.
详细描述
In this study, 100 professional boxers that experience a concussion will be enrolled, randomized to either placebo or sildenafil (60mg) drug treatment, and arterial spin labeling and BOLD-MRI with hypercapnia will used to assess CBF and CVR, respectively. Symptom reporting, blood biomarkers, and neuropsychological testing will also be conducted. The timepoints for this study are baseline (pre-fight), and once between days 1 and 3 and day 30 after injury.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
盲法说明
Investigators associated with this study will not have access to the randomization schedule. The principal investigator, study team, and study subjects will be blinded in this study.
入排标准
- 年龄范围
- 18 Years 至 35 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •For Athletes
- •Male or female professional boxers/MMA fighters
- •Ability to undergo MR imaging procedures
- •At least one of the following:
- •Knockout (KO)/Technical Knockout (TKO) scored by fight referee.
- •Greater than 25 blows to the head.
- •Significant post-concussive symptoms (Symptom Score > 1 on at least 3 items from the Rivermead Post-Concussion Questionnaire)
- •For Controls
- •Male of female who do not participate in contact sports
- •Screen negative for mild TBI (mTBI) using Ohio State TBI Identification
排除标准
- •Contraindication to sildenafil which includes the following:
- •Current use of organic nitrate vasodilators
- •Use of ritonavir (HIV-protease inhibitor)
- •Current use of erythromycin, ketoconazole, or itraconazole
- •Current use of cimetidine
- •Current resting hypotension (BP < 90/50 mm Hg)
- •Current severe renal insufficiency (Creatinine Clearance < 30 milliliters/minute)
- •Current hepatic cirrhosis
- •Current cardiac failure or coronary artery disease causing unstable angina
- •Retinitis pigmentosa
- •Known hypersensitivity or allergy to sildenafil of any of its components
- •Daily therapy with a PDE5 inhibitor within the past 2 months
- •Immediate hospitalization for severe concussion
- •History of neurological or psychiatric disorder not related to TBI
- •Known inclusion in another interventional clinical trial
- •Subjects with metal implants that would interfere with the MR imaging procedures
- •Sickle cell disease
- •History of priapism
研究组 & 干预措施
Placebo oral capsule
If randomized to placebo, the participant will receive single (Group 1) or multiple (once-a-day for 14 days; Group 2) treatments.
干预措施: Placebo oral capsule (Drug)
Sildenafil Citrate
If randomized to sildenafil (60mg), the participant will receive single (Group 1) or multiple (once-a-day for 14 days; Group 2) treatments.
干预措施: Sildenafil Citrate (Drug)
结局指标
主要结局
Arterial Spin Labeling
时间窗: 3 years
Prior to and after sildenafil treatment (60mg) cerebral blood flow will be measured in the athletes and healthy controls.
次要结局
- BOLD MRI With Hypercapnia(3 years)
- Rivermead Post Concussion Symptoms Questionnaire (RPQ)(3 years)
- Hopkins Verbal Learning Task (HVLT)(3 years)
研究者
Kan Ding
Assistant Professor
University of Texas Southwestern Medical Center