Androgen Deprivation Therapy, Autonomic Dysfunction, Hypertension, Prostate Cancer, Renal Disease
Conditions
Brief summary
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.
Interventions
DRUGGonadotropin Releasing Hormone Agonists (GNRH)
8 weeks of GnRH agonist
2 weeks of AR Inhibitor
DRUGPlacebo
Placebo tablet and injection
Sponsors
University of Colorado, Denver
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
MALE
Age
40 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* -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
Exclusion criteria
* -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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Cardiovagal Baroreflex Sensitivity | 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 Blood Pressure Reactivity to the Cold Pressor Test | 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 | 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 Ambulatory Blood Pressure Variability | 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 | 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 | 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 Renal Dysfunction Biomarkers | 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. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORMatthew Babcock, PhD
University of Colorado, Denver
Participant flow
Recruitment details
Participants were recruited from the Denver Metro area between September 2023 and June 2025. The first participant was enrolled on September 20, 2023 and the last participant was enrolled in April 2025.
Pre-assignment details
A total of 277 men expressed interest in participating in the study. Of these, 234 were determined ineligible or were not interested after receiving a description of the study and 43 reported for consent and screening. Thirty three were not eligible and 10 were enrolled into the study.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants |
| Body Mass Index | 25.8 kg/m2 STANDARD_DEVIATION 2.8 |
| Diastolic Blood Pressure | 80 mmHg STANDARD_DEVIATION 4 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 8 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 3 Participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 0 Participants |
| Systolic Blood Pressure | 125 mmHg STANDARD_DEVIATION 8 |
| Total Testosterone | 491 ng/dL STANDARD_DEVIATION 144 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 0 | 0 / 4 | 0 / 6 |
| other Total, other adverse events | 0 / 0 | 0 / 4 | 0 / 6 |
| serious Total, serious adverse events | 0 / 0 | 0 / 4 | 0 / 6 |
Outcome results
None listed