Autonomic and Renal Contributions to Hypertension With Androgen Deprivation Therapy
试验速览
- 阶段
- 4 期
- 状态
- 终止
- 入组人数
- 10
- 试验地点
- 2
- 主要终点
- Change in blood pressure reactivity to the cold pressor test
研究概览
简要总结
This study plans to learn more about contributors to high blood pressure in men who undergo androgen deprivation therapy (ADT) to treat prostate cancer. Prostate cancer is the most common non-skin cancer in men, affecting approximately 1 in 8 American men and its primary treatment is through the use of ADT. However, ADT increases the likelihood of developing heart disease including high blood pressure. This study will determine if dysfunction of the nervous system and/or kidneys occurs in men undergoing ADT, as these systems play a significant role in control of blood pressure. The results from this study will help us understand the ways in which ADT contributes to heart disease and help us develop therapies to prevent heart disease in prostate cancer survivors.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 40 Years 至 —（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •-age 40+ years;
- •resting blood pressure <140/90 mmHg;
- •fasted blood glucose <126 mg/dL;
- •testosterone ≥400 ng/dL;
- •sedentary to recreationally active;
- •nonsmokers;
- •healthy as determined by medical history, physical exam, blood and urine chemistries and resting and exercise ECG during a physician supervised graded exercise treadmill test OR recent diagnosis of non-metastatic prostate cancer with plans to undergo androgen deprivation therapy;
- •PSA <4.00 ng/dL if in the non-cancer group;
- •Gleason Score ≤7 if in the prostate cancer group;
- •no use of medications that might influence cardiovascular function (e.g., antihypertensives, lipid-lowering medications);
- •willing and able to be on GnRHagonist and AR inhibitor;
- •not taking antioxidant vitamins, corticosteroids, or anti-inflammatory medications, or willing to stop use for four weeks prior to the start of the study;
- •not using exogenous sex hormones for at least one year
排除标准
- •-acute liver disease;
- •chronic kidney disease, serum creatinine >1.3 mg/dL, macroalbuminuria >300 mg/g of proteinuria
- •pre-existing or active cardiac, renal or hepatic disease, epilepsy or other seizure disorder;
- •diabetes, active or chronic infection, disease that affects the nervous system;
- •Gleason Score ≥8;
- •thyroid dysfunction, defined as ultrasensitive TSH <0.5 or >5.0 mU/L, volunteers with abnormal TSH values will be re-considered for participation after follow-up evaluation by the PCP with initiation or adjustment of thyroid hormone replacement;
- •tobacco use within the previous 12 months
研究组 & 干预措施
Healthy + Placebo
Healthy men undergoing placebo for 9 weeks.
干预措施: Placebo (Drug)
Prostate Cancer
Men undergoing androgen deprivation therapy via gonadotropin releasing hormone agonist plus androgen receptor inhibitor for the treatment of prostate cancer
干预措施: Androgen receptor (AR) inhibitor (Drug)
Prostate Cancer
Men undergoing androgen deprivation therapy via gonadotropin releasing hormone agonist plus androgen receptor inhibitor for the treatment of prostate cancer
干预措施: Gonadotropin Releasing Hormone Agonists (GNRH) (Drug)
Healthy + ADT
Healthy men undergoing gonadal suppression via gonadotropin releasing hormone agonist plus androgen receptor inhibitor for 9 weeks
干预措施: Gonadotropin Releasing Hormone Agonists (GNRH) (Drug)
Healthy + ADT
Healthy men undergoing gonadal suppression via gonadotropin releasing hormone agonist plus androgen receptor inhibitor for 9 weeks
干预措施: Androgen receptor (AR) inhibitor (Drug)
结局指标
主要结局
Change in blood pressure reactivity to the cold pressor test
时间窗: Before and after 9 weeks of androgen deprivation therapy or placebo
The change in blood pressure will be assessed from quiet rest to sympathetic activation using the cold pressor test
Change in beat-to-beat blood pressure variability
时间窗: Before and after 9 weeks of androgen deprivation therapy or placebo
Beat-to-beat blood pressure variability will be using finger photoplethysmography measured in the laboratory.
Change in exercise pressor reflex
时间窗: Before and after 9 weeks of androgen deprivation therapy or placebo
The change in blood pressure will be assessed from quiet rest to isometric handgrip exercise
Change in renal vascular resistance
时间窗: Before and after 9 weeks of androgen deprivation therapy or placebo
Renal blood flow will be determined using ultrasound and blood pressure will be determined using finger photoplethysmography. These measures will be used to estimate renal vascular resistance.
Change in ambulatory blood pressure variability
时间窗: Before and after 9 weeks of androgen deprivation therapy or placebo
Ambulatory blood pressure variability will be determined from 24-hour ambulatory blood pressure monitoring.
Change in Renal dysfunction biomarkers
时间窗: Before and after 9 weeks of androgen deprivation therapy or placebo
Neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule (KIM)-1, interleukin (IL)-18, and vanin-1 will be quantified in urine using commercially available assay kits. Concentrations will be normalized to urinary flow rate.
Change in Blood Pressure Reactivity to the Cold Pressor Test
时间窗: Before and after 9 weeks of androgen deprivation therapy or placebo
The change in systolic blood pressure will be assessed from quiet rest to sympathetic activation using the cold pressor test
Change in Exercise Pressor Reflex
时间窗: Before and after 9 weeks of androgen deprivation therapy or placebo
The change in systolic blood pressure will be assessed from quiet rest to isometric handgrip exercise
Change in Cardiovagal Baroreflex Sensitivity
时间窗: Before and after 9 weeks of androgen deprivation therapy or placebo
The change in cardiovagal baroreflex sensitivity will be assessed via the sequence method
Change in Renal Dysfunction Biomarkers
时间窗: Before and after 9 weeks of androgen deprivation therapy or placebo
Neutrophil gelatinase-associated lipocalin (NGAL), tissue inhibitor of metalloproteinases 2 (TIMP2), and insulin-like growth factor binding protein 7 (IGFBP7) will be quantified in urine using commercially available assay kits. Concentrations will be normalized to urinary flow rate.
Change in Ambulatory Blood Pressure Variability
时间窗: Before and after 9 weeks of androgen deprivation therapy or placebo
Ambulatory systolic blood pressure variability will be determined from 24-hour ambulatory blood pressure monitoring using the standard deviation of blood pressure readings
Change in Beat-to-beat Blood Pressure Variability
时间窗: Before and after 9 weeks of androgen deprivation therapy or placebo
Beat-to-beat systolic blood pressure variability will be determined using the standard deviation of blood pressure readings from finger photoplethysmography measured in the laboratory.
Change in Renal Vascular Resistance
时间窗: Before and after 9 weeks of androgen deprivation therapy or placebo
Renal blood flow will be determined using ultrasound and blood pressure will be determined using finger photoplethysmography. These measures will be used to estimate renal vascular resistance.
次要结局
- Change in Sympathetic reactivity(Before and after 9 weeks of androgen deprivation therapy or placebo)
- Change in sympathetic baroreflex sensitivity(Before and after 9 weeks of androgen deprivation therapy or placebo)
- Change in glomerular filtration rate(Before and after 9 weeks of androgen deprivation therapy or placebo)
- Change in renal plasma flow(Before and after 9 weeks of androgen deprivation therapy or placebo)