Contributions to Hypertension With Androgen Deprivation Therapy

Clinicaltrials.gov ID: NCT05700903
db-list-check Status RECRUITING
b-loader Phase PHASE4
b-people Age ≥ 40 Years
b-bullseye-arrow Enrollments 228

Conditions

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

Drugs

Gonadotropin Releasing Hormone Agonists (GNRH), Androgen receptor (AR) inhibitor, Placebo

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.

Locations

1 location Found with status Recruiting

Status

  • RECRUITING

Contact Person

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 agonist
  • DRUG:

    Androgen receptor (AR) inhibitor

    Description:

    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 agonist
  • DRUG:

    Androgen receptor (AR) inhibitor

    Description:

    2 weeks of AR Inhibitor

Healthy + Placebo

PLACEBO_COMPARATOR

Healthy men undergoing placebo for 9 weeks.

  • DRUG:

    Placebo

    Description:

    Placebo tablet and injection

Outcome Measures

Primary Outcome Measures

Change in Cardiovagal Baroreflex Sensitivity

Time Frame: Before and after 9 weeks of androgen deprivation therapy or placebo

Change in blood pressure reactivity to the cold pressor test

Time Frame: Before and after 9 weeks of androgen deprivation therapy or placebo

Change in exercise pressor reflex

Time Frame: Before and after 9 weeks of androgen deprivation therapy or placebo

Change in ambulatory blood pressure variability

Time Frame: Before and after 9 weeks of androgen deprivation therapy or placebo

Change in beat-to-beat blood pressure variability

Time Frame: Before and after 9 weeks of androgen deprivation therapy or placebo

Change in renal vascular resistance

Time Frame: Before and after 9 weeks of androgen deprivation therapy or placebo

Change in Renal dysfunction biomarkers

Time Frame: Before and after 9 weeks of androgen deprivation therapy or placebo

Secondary Outcome Measures

Change in sympathetic baroreflex sensitivity

Time Frame: Before and after 9 weeks of androgen deprivation therapy or placebo

Change in Sympathetic reactivity

Time Frame: Before and after 9 weeks of androgen deprivation therapy or placebo

Change in glomerular filtration rate

Time Frame: Before and after 9 weeks of androgen deprivation therapy or placebo

Change in renal plasma flow

Time Frame: Before and after 9 weeks of androgen deprivation therapy or placebo

Timeline

  • Last Updated
    June 12, 2024
  • Start Date
    January 26, 2023
  • Today
    January 16, 2025
  • Completion Date ( Estimated )
    March 31, 2028

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