Contributions to Hypertension With Androgen Deprivation Therapy

Hypertension Clinical Trial

— ARCH  

Official title:

Autonomic and Renal Contributions to Hypertension With Androgen Deprivation Therapy

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05700903
• Other study ID #: 22-2201.cc
• Status: Recruiting
• Phase: Phase 4
• Start date: September 20, 2023
• Est. completion date: March 31, 2028

Study information

• Verified date: November 2023
• Source: University of Colorado, Denver
• Contact: Matthew Babcock, PhD
• Phone: 303-724-1401
• Email: matthew.babcock[@]cuanschutz.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 228
• Est. completion date: March 31, 2028
• Est. primary completion date: March 31, 2028
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 40 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Androgen Deprivation Therapy
• Autonomic Dysfunction
• Autonomic Nervous System Diseases
• Hypertension
• Primary Dysautonomias
• Prostate Cancer
• Renal Disease

Intervention

Drug:
• Gonadotropin-Releasing Hormone Agonist
8 weeks of GnRH agonist
• Androgen receptor inhibitor
2 weeks of AR Inhibitor
• Placebo
Placebo tablet and injection

Locations

Country	Name	City	State
United States	UCHealth University of Colorado Hospital	Aurora	Colorado

Sponsors (1)

Lead Sponsor	Collaborator
University of Colorado, Denver

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Change in Inflammation	Proteomic analysis of inflammatory cascade proteins will be quantified in plasma samples.	Before and after 9 weeks of androgen deprivation therapy or placebo
Other	Change in Oxidative stress	Whole blood reactive oxygen species will be measured in from venous blood samples using electron paramagnetic resonance spectroscopy	Before and after 9 weeks of androgen deprivation therapy or placebo
Other	Change in Body composition	Descriptive variable total body fat mass (for screening and to document any changes with the intervention)	Before and after 9 weeks of androgen deprivation therapy or placebo
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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	Change in sympathetic baroreflex sensitivity	Changes in muscle sympathetic nerve activity in response to changes in blood pressure will be assessed using the modified Oxford procedure	Before and after 9 weeks of androgen deprivation therapy or placebo
Secondary	Change in Sympathetic reactivity	The change in muscle sympathetic nerve activity 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
Secondary	Change in glomerular filtration rate	Glomerular filtration rate and renal plasma flow will be calculated by iohexol (Omnipaque 300, GE Healthcare) clearance technique. Plasma and urine iohexol and p-aminohippurate clearance will be measured on a High-Performance Liquid Chromatography (HPLC, Waters, Milford, MA).	Before and after 9 weeks of androgen deprivation therapy or placebo
Secondary	Change in renal plasma flow	Renal plasma flow will be calculated by p-aminohippurate (Basic Pharma) clearance techniques. Plasma and urine p-aminohippurate clearance will be measured on a High-Performance Liquid Chromatography (HPLC, Waters, Milford, MA).	Before and after 9 weeks of androgen deprivation therapy or placebo