Contributions to Hypertension With Androgen Deprivation Therapy

NCT05700903 | Completed Phase 4 DMC FDA Drug

• 1 other identifier: 22-2201.cc
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

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.

Conditions

Prostate Cancer; Hypertension; Autonomic Dysfunction; Renal Disease; Androgen Deprivation Therapy

Outcome Measures

Primary Outcomes (7)

• 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

• 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

Secondary Outcomes (4)

• Change in sympathetic baroreflex sensitivity

  Before and after 9 weeks of androgen deprivation therapy or placebo

• Change in Sympathetic reactivity

  Before and after 9 weeks of androgen deprivation therapy or placebo

• Change in glomerular filtration rate

  Before and after 9 weeks of androgen deprivation therapy or placebo

• Change in renal plasma flow

  Before and after 9 weeks of androgen deprivation therapy or placebo

Other Outcomes (3)

• Change in Inflammation

  Before and after 9 weeks of androgen deprivation therapy or placebo

• Change in Oxidative stress

  Before and after 9 weeks of androgen deprivation therapy or placebo

• Change in Body composition

  Before and after 9 weeks of androgen deprivation therapy or placebo

Study Arms (3)

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); Drug: Androgen receptor (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); Drug: Androgen receptor (AR) inhibitor

Healthy + Placebo

PLACEBO COMPARATOR

Healthy men undergoing placebo for 9 weeks.

Drug: Placebo

Interventions

Gonadotropin Releasing Hormone Agonists (GNRH) DRUG

8 weeks of GnRH agonist

Also known as: Leuprolide, Goserelin

Healthy + ADT; Prostate Cancer

Androgen receptor (AR) inhibitor DRUG

2 weeks of AR Inhibitor

Also known as: Bicalutamide, Flutamide, Enzalutamide

Healthy + ADT; Prostate Cancer

Placebo DRUG

Placebo tablet and injection

Healthy + Placebo

Eligibility Criteria

• Age: 40 Years+
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Colorado, Denver: lead

Study Sites (1)

UCHealth University of Colorado Hospital

Aurora, Colorado, 80045, United States

Location

MeSH Terms

Conditions

Prostatic Neoplasms; Hypertension; Primary Dysautonomias; Kidney Diseases

Interventions

Leuprolide; Goserelin; Receptors, Androgen; bicalutamide; Flutamide; enzalutamide

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases; Vascular Diseases; Cardiovascular Diseases; Autonomic Nervous System Diseases; Nervous System Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications

Intervention Hierarchy (Ancestors)

Gonadotropin-Releasing Hormone; Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins; Receptors, Steroid; Receptors, Cytoplasmic and Nuclear; Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines

Study Officials

• Matthew Babcock, PhD

  University of Colorado, Denver

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 10, 2023
• First Posted: January 26, 2023
• Study Start: September 20, 2023
• Primary Completion: July 16, 2025
• Study Completion: July 16, 2025
• Last Updated: March 2, 2026

Record last verified: 2025-10

Locations

US (1)