Contributions to Hypertension With Androgen Deprivation Therapy (ARCH)

University of Colorado Denver (CU Denver)

Status and phase: Completed; Phase 4

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

Treatments: Drug: Placebo; Drug: Androgen receptor (AR) inhibitor; Drug: Gonadotropin Releasing Hormone Agonists (GNRH)

Study type: Interventional

Funder types: Other

Identifiers

NCT05700903

22-2201.cc

Details and patient eligibility

About

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.

Enrollment: 10 patients

Sex: Male

Ages: 40+ years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

---

10 participants in 3 patient groups, including a placebo group

Prostate Cancer

Active Comparator group

Description:

Men undergoing androgen deprivation therapy via gonadotropin releasing hormone agonist plus androgen receptor inhibitor for the treatment of prostate cancer

Treatment:

Drug: Gonadotropin Releasing Hormone Agonists (GNRH)

Drug: Androgen receptor (AR) inhibitor

Healthy + ADT

Active Comparator group

Description:

Healthy men undergoing gonadal suppression via gonadotropin releasing hormone agonist plus androgen receptor inhibitor for 9 weeks

Treatment:

Drug: Gonadotropin Releasing Hormone Agonists (GNRH)

Drug: Androgen receptor (AR) inhibitor

Healthy + Placebo

Placebo Comparator group

Description:

Healthy men undergoing placebo for 9 weeks.

Treatment:

Drug: Placebo