Clinical trial NCT05700903: Contributions to Hypertension With Androgen Deprivation Therapy
Official title: Autonomic and Renal Contributions to Hypertension With Androgen Deprivation Therapy
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Androgen Deprivation Therapy
Prostate Cancer
Hypertension
Autonomic Dysfunction
Renal Disease
Lead sponsor: University of Colorado, Denver
Sponsor class: OTHER
First posted: 2023-01-26
Enrollment: 228
Sex: MALE
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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.


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

Primary outcomes:
measure: Change in Cardiovagal Baroreflex Sensitivity
timeFrame: Before and after 9 weeks of androgen deprivation therapy or placebo
measure: Change in blood pressure reactivity to the cold pressor test
timeFrame: Before and after 9 weeks of androgen deprivation therapy or placebo
measure: Change in exercise pressor reflex
timeFrame: Before and after 9 weeks of androgen deprivation therapy or placebo
measure: Change in ambulatory blood pressure variability
timeFrame: Before and after 9 weeks of androgen deprivation therapy or placebo
measure: Change in beat-to-beat blood pressure variability
timeFrame: Before and after 9 weeks of androgen deprivation therapy or placebo
measure: Change in renal vascular resistance
timeFrame: Before and after 9 weeks of androgen deprivation therapy or placebo
measure: Change in Renal dysfunction biomarkers
timeFrame: Before and after 9 weeks of androgen deprivation therapy or placebo
Secondary outcomes:
measure: Change in sympathetic baroreflex sensitivity
timeFrame: Before and after 9 weeks of androgen deprivation therapy or placebo
measure: Change in Sympathetic reactivity
timeFrame: Before and after 9 weeks of androgen deprivation therapy or placebo
measure: Change in glomerular filtration rate
timeFrame: Before and after 9 weeks of androgen deprivation therapy or placebo
measure: Change in renal plasma flow
timeFrame: Before and after 9 weeks of androgen deprivation therapy or placebo
Other outcomes:
measure: Change in Inflammation
timeFrame: Before and after 9 weeks of androgen deprivation therapy or placebo
measure: Change in Oxidative stress
timeFrame: Before and after 9 weeks of androgen deprivation therapy or placebo
measure: Change in Body composition
timeFrame: Before and after 9 weeks of androgen deprivation therapy or placebo
Locations:
city: Aurora
country: United States
facility: UCHealth University of Colorado Hospital
state: Colorado
Study officials:
affiliation: University of Colorado, Denver
name: Matthew Babcock, PhD
role: PRINCIPAL_INVESTIGATOR
References: