This trial tests the effect of androgen deprivation therapy (ADT) on blood pressure in healthy men, as well as patients with prostate cancer. Androgens are hormones that promote the development and maintenance of male sex characteristics. Androgen contributes to the development of hormone-sensitive prostate cancer. Although ADT may reduce the growth of prostate cancer, it increases the risk of cardiovascular disease. Bicalutamide is in a class of medications called nonsteroidal antiandrogen. It binds to proteins called androgen receptors, blocking these proteins and may keep cancer cells from growing. Leuprolide is in a class of medications called gonadotropin-releasing hormone agonist. It prevents the body from making luteinizing hormone-releasing hormone (LHRH) and luteinizing hormone (LH). This causes the testicles to stop making testosterone (a male hormone) in men and may stop the growth of prostate cancer cells that need testosterone to grow. This study will examine if low testosterone induced by androgen deprivation therapy may contribute to worsening cardiovascular health. Specifically, to see if the increased likelihood of developing high blood pressure in men who undergo androgen deprivation therapy is because of dysfunction of the kidneys and/or nervous system, two essential regulators of blood pressure. Understanding how ADT increases the cardiovascular (CV) risk in patients with prostate cancer may help researchers develop therapies to prevent heart disease in men who undergo ADT treatment.
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT05700903.
PRIMARY OBJECTIVES:
I. Determine whether ADT alters neural control of the CV system.
II. Determine whether ADT increases biomarkers of impaired renal function.
EXPLORATORY OBJECTIVE:
I. To obtain insight into cellular mechanisms that contribute to neural and/or renal dysfunction in men undergoing ADT, we will quantify inflammation in men with prostate cancer before and after 8 weeks of ADT and healthy men before or after 8 weeks of ADT or placebo.
OUTLINE:
CANCER PATIENTS: Patients receive bicalutamide orally (PO) daily (QD) on days 0-14 and leuprolide injection on days 8 and 35. Patients undergo blood sample collection at screening, baseline and throughout study. Patients undergo urine sample collection and undergo diagnostic testing including renal ultrasound, electrocardiogram, dual X-ray absorptiometry, treadmill testing, modified oxford procedure, isometric handgrip exercises, cold pressor test and microneurography testing at baseline and throughout study. Patients also undergo blood pressure monitoring and wear ActivPal to monitor activity while on study. Patients undergo laboratory testing for isohexal and para aminohippurate (PAH) clearance testing, glomerular filtration rate and renal plasma while on study. Patients may optionally undergo echocardiography on study.
Healthy participants are randomized to 1 of 2 arms.
ARM I: Participants receive bicalutamide PO QD on days 0-14 and leuprolide injection on days 8 and 35. Patients undergo blood sample collection at screening, baseline and throughout study. Patients undergo urine sample collection and undergo diagnostic testing including renal ultrasound, pulse oximetry, electrocardiogram, dual X-ray absorptiometry, treadmill testing, modified oxford procedure, isometric handgrip exercises, cold pressor test and microneurography testing at baseline and throughout study. Patients also undergo blood pressure monitoring and wear ActivPal to monitor activity while on study. Patients undergo laboratory testing for isohexal and PAH clearance testing, glomerular filtration rate and renal plasma while on study. Patients may optionally undergo echocardiography on study.
ARM II: Participants receive placebo PO QD on days 0-14 and placebo injection on days 8 and 35. Patients undergo blood sample collection at screening, baseline and throughout study. Patients undergo urine sample collection and undergo diagnostic testing including renal ultrasound, pulse oximetry, electrocardiogram, dual X-ray absorptiometry, treadmill testing, modified oxford procedure, isometric handgrip exercises, cold pressor test and microneurography testing at baseline and throughout study. Patients also undergo blood pressure monitoring and wear ActivPal to monitor activity while on study. Patients undergo laboratory testing for isohexal and PAH clearance testing, glomerular filtration rate and renal plasma while on study. Patients may optionally undergo echocardiography on study.
Lead OrganizationUCHealth University of Colorado Hospital
Principal InvestigatorMatthew Babcock
