Contributions to Hypertension With Androgen Deprivation Therapy
Conditions
Androgen Deprivation Therapy, Prostate Cancer, Hypertension, Autonomic Dysfunction, Renal DiseaseDrugs
Gonadotropin Releasing Hormone Agonists (GNRH), Androgen receptor (AR) inhibitor, PlaceboSummary
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.
Locations
1 location Found with status Recruiting
Status
- RECRUITING
Contact Person
- Matthew Babcock, PhD
- 720-848-6470
- [email protected]
Principal Investigator
- Matthew Babcock, PhD
Eligibility Criteria
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
Study Plan
Prostate Cancer
ACTIVE_COMPARATOR
Men undergoing androgen deprivation therapy via gonadotropin releasing hormone agonist plus androgen receptor inhibitor for the treatment of prostate cancer
DRUG:
Gonadotropin Releasing Hormone Agonists (GNRH)Description:
8 weeks of GnRH agonistDRUG:
Androgen receptor (AR) inhibitorDescription:
2 weeks of AR Inhibitor
Healthy + ADT
ACTIVE_COMPARATOR
Healthy men undergoing gonadal suppression via gonadotropin releasing hormone agonist plus androgen receptor inhibitor for 9 weeks
DRUG:
Gonadotropin Releasing Hormone Agonists (GNRH)Description:
8 weeks of GnRH agonistDRUG:
Androgen receptor (AR) inhibitorDescription:
2 weeks of AR Inhibitor
Healthy + Placebo
PLACEBO_COMPARATOR
Healthy men undergoing placebo for 9 weeks.
DRUG:
PlaceboDescription:
Placebo tablet and injection
Outcome Measures
Primary Outcome Measures
Change in Cardiovagal Baroreflex Sensitivity
Change in blood pressure reactivity to the cold pressor test
Change in exercise pressor reflex
Change in ambulatory blood pressure variability
Change in beat-to-beat blood pressure variability
Change in renal vascular resistance
Change in Renal dysfunction biomarkers
Secondary Outcome Measures
Change in sympathetic baroreflex sensitivity
Change in Sympathetic reactivity
Change in glomerular filtration rate
Change in renal plasma flow
Timeline
Last Updated
June 12, 2024Start Date
January 26, 2023Today
February 5, 2025Completion Date ( Estimated )
March 31, 2028
Sponsors of this trial
Lead Sponsor
University of Colorado, Denver