Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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.
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Prostate Cancer | Active Comparator | Men undergoing androgen deprivation therapy via gonadotropin releasing hormone agonist plus androgen receptor inhibitor for the treatment of prostate cancer |
|
| Healthy + ADT | Active Comparator | Healthy men undergoing gonadal suppression via gonadotropin releasing hormone agonist plus androgen receptor inhibitor for 9 weeks |
|
| Healthy + Placebo | Placebo Comparator | Healthy men undergoing placebo for 9 weeks. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Gonadotropin Releasing Hormone Agonists (GNRH) | Drug | 8 weeks of GnRH agonist |
|
| Measure | Description | Time Frame |
|---|---|---|
| Change in Cardiovagal Baroreflex Sensitivity | The change in cardiovagal baroreflex sensitivity will be assessed the modified Oxford procedure | Before and after 9 weeks of androgen deprivation therapy or placebo |
| Change in blood pressure reactivity to the cold pressor test | The change in blood pressure will be assessed from quiet rest to sympathetic activation using the cold pressor test | Before and after 9 weeks of androgen deprivation therapy or placebo |
| Change in exercise pressor reflex | The change in blood pressure will be assessed from quiet rest to isometric handgrip exercise | Before and after 9 weeks of androgen deprivation therapy or placebo |
| Change in ambulatory blood pressure variability | Ambulatory blood pressure variability will be determined from 24-hour ambulatory blood pressure monitoring. | Before and after 9 weeks of androgen deprivation therapy or placebo |
| Change in beat-to-beat blood pressure variability | Beat-to-beat blood pressure variability will be using finger photoplethysmography measured in the laboratory. | Before and after 9 weeks of androgen deprivation therapy or placebo |
| Change in renal vascular resistance | 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. | Before and after 9 weeks of androgen deprivation therapy or placebo |
| Measure | Description | Time Frame |
|---|---|---|
| Change in sympathetic baroreflex sensitivity | Changes in muscle sympathetic nerve activity in response to changes in blood pressure will be assessed using the modified Oxford procedure | Before and after 9 weeks of androgen deprivation therapy or placebo |
| Change in Sympathetic reactivity |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Inflammation | Proteomic analysis of inflammatory cascade proteins will be quantified in plasma samples. | Before and after 9 weeks of androgen deprivation therapy or placebo |
| Change in Oxidative stress |
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Matthew Babcock, PhD | University of Colorado, Denver | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| UCHealth University of Colorado Hospital | Aurora | Colorado | 80045 | United States |
Not provided
| ID | Term |
|---|---|
| D011471 | Prostatic Neoplasms |
| D006973 | Hypertension |
| D054969 | Primary Dysautonomias |
| D007674 | Kidney Diseases |
| ID | Term |
|---|---|
| D005834 | Genital Neoplasms, Male |
| D014565 | Urogenital Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
Not provided
Not provided
| ID | Term |
|---|---|
| D016729 | Leuprolide |
| D017273 | Goserelin |
| D011944 | Receptors, Androgen |
| C053541 | bicalutamide |
| D005485 | Flutamide |
| C540278 | enzalutamide |
| ID | Term |
|---|---|
| D007987 | Gonadotropin-Releasing Hormone |
| D010906 | Pituitary Hormone-Releasing Hormones |
| D007028 | Hypothalamic Hormones |
| D036361 | Peptide Hormones |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Androgen receptor (AR) inhibitor | Drug | 2 weeks of AR Inhibitor |
|
|
| Placebo | Drug | Placebo tablet and injection |
|
| Change in Renal dysfunction biomarkers | 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. | Before and after 9 weeks of androgen deprivation therapy or placebo |
The change in muscle sympathetic nerve activity will be assessed from quiet rest to sympathetic activation using the cold pressor test. |
| Before and after 9 weeks of androgen deprivation therapy or placebo |
| Change in glomerular filtration rate | Glomerular filtration rate and renal plasma flow will be calculated by iohexol (Omnipaque 300, GE Healthcare) clearance technique. Plasma and urine iohexol and p-aminohippurate clearance will be measured on a High-Performance Liquid Chromatography (HPLC, Waters, Milford, MA). | Before and after 9 weeks of androgen deprivation therapy or placebo |
| Change in renal plasma flow | Renal plasma flow will be calculated by p-aminohippurate (Basic Pharma) clearance techniques. Plasma and urine p-aminohippurate clearance will be measured on a High-Performance Liquid Chromatography (HPLC, Waters, Milford, MA). | Before and after 9 weeks of androgen deprivation therapy or placebo |
Whole blood reactive oxygen species will be measured in from venous blood samples using electron paramagnetic resonance spectroscopy
| Before and after 9 weeks of androgen deprivation therapy or placebo |
| Change in Body composition | Descriptive variable total body fat mass (for screening and to document any changes with the intervention) | Before and after 9 weeks of androgen deprivation therapy or placebo |
| D005832 |
| Genital Diseases, Male |
| D000091662 | Genital Diseases |
| D000091642 | Urogenital Diseases |
| D011469 | Prostatic Diseases |
| D052801 | Male Urogenital Diseases |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D001342 | Autonomic Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D014570 | Urologic Diseases |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D006728 | Hormones |
| D006730 | Hormones, Hormone Substitutes, and Hormone Antagonists |
| D009479 | Neuropeptides |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
| D009842 | Oligopeptides |
| D009419 | Nerve Tissue Proteins |
| D011506 | Proteins |
| D011987 | Receptors, Steroid |
| D018160 | Receptors, Cytoplasmic and Nuclear |
| D000813 | Anilides |
| D000577 | Amides |
| D009930 | Organic Chemicals |
| D000814 | Aniline Compounds |
| D000588 | Amines |