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Contributions to Hypertension With Androgen Deprivation Therapy (ARCH)

Primary Purpose

Androgen Deprivation Therapy, Prostate Cancer, Hypertension

Status
Not yet recruiting
Phase
Phase 4
Locations
Study Type
Interventional
Intervention
Gonadotropin-Releasing Hormone Agonist
Androgen receptor inhibitor
Placebo
Sponsored by
University of Colorado, Denver
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional other trial for Androgen Deprivation Therapy

Eligibility Criteria

40 Years - undefined (Adult, Older Adult)MaleAccepts 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

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm 3

    Arm Type

    Active Comparator

    Active Comparator

    Placebo Comparator

    Arm Label

    Prostate Cancer

    Healthy + ADT

    Healthy + Placebo

    Arm Description

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

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

    Healthy men undergoing placebo for 9 weeks.

    Outcomes

    Primary Outcome Measures

    Change in Cardiovagal Baroreflex Sensitivity
    The change in cardiovagal baroreflex sensitivity will be assessed the modified Oxford procedure
    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
    Change in exercise pressor reflex
    The change in blood pressure will be assessed from quiet rest to isometric handgrip exercise
    Change in ambulatory blood pressure variability
    Ambulatory blood pressure variability will be determined from 24-hour ambulatory blood pressure monitoring.
    Change in beat-to-beat blood pressure variability
    Beat-to-beat blood pressure variability will be using finger photoplethysmography measured in the laboratory.
    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.
    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.

    Secondary Outcome Measures

    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
    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.
    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).
    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).

    Full Information

    First Posted
    January 10, 2023
    Last Updated
    August 14, 2023
    Sponsor
    University of Colorado, Denver
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    1. Study Identification

    Unique Protocol Identification Number
    NCT05700903
    Brief Title
    Contributions to Hypertension With Androgen Deprivation Therapy
    Acronym
    ARCH
    Official Title
    Autonomic and Renal Contributions to Hypertension With Androgen Deprivation Therapy
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    August 2023
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    October 1, 2023 (Anticipated)
    Primary Completion Date
    March 31, 2028 (Anticipated)
    Study Completion Date
    March 31, 2028 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    University of Colorado, Denver

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    Yes
    Studies a U.S. FDA-regulated Device Product
    No
    Data Monitoring Committee
    Yes

    5. Study Description

    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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Androgen Deprivation Therapy, Prostate Cancer, Hypertension, Autonomic Dysfunction, Renal Disease

    7. Study Design

    Primary Purpose
    Other
    Study Phase
    Phase 4
    Interventional Study Model
    Parallel Assignment
    Masking
    ParticipantInvestigatorOutcomes Assessor
    Allocation
    Randomized
    Enrollment
    228 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Prostate Cancer
    Arm Type
    Active Comparator
    Arm Description
    Men undergoing androgen deprivation therapy via gonadotropin releasing hormone agonist plus androgen receptor inhibitor for the treatment of prostate cancer
    Arm Title
    Healthy + ADT
    Arm Type
    Active Comparator
    Arm Description
    Healthy men undergoing gonadal suppression via gonadotropin releasing hormone agonist plus androgen receptor inhibitor for 9 weeks
    Arm Title
    Healthy + Placebo
    Arm Type
    Placebo Comparator
    Arm Description
    Healthy men undergoing placebo for 9 weeks.
    Intervention Type
    Drug
    Intervention Name(s)
    Gonadotropin-Releasing Hormone Agonist
    Other Intervention Name(s)
    Leuprolide, Goserelin
    Intervention Description
    8 weeks of GnRH agonist
    Intervention Type
    Drug
    Intervention Name(s)
    Androgen receptor inhibitor
    Other Intervention Name(s)
    Bicalutamide, Flutamide, Enzalutamide
    Intervention Description
    2 weeks of AR Inhibitor
    Intervention Type
    Drug
    Intervention Name(s)
    Placebo
    Intervention Description
    Placebo tablet and injection
    Primary Outcome Measure Information:
    Title
    Change in Cardiovagal Baroreflex Sensitivity
    Description
    The change in cardiovagal baroreflex sensitivity will be assessed the modified Oxford procedure
    Time Frame
    Before and after 9 weeks of androgen deprivation therapy or placebo
    Title
    Change in blood pressure reactivity to the cold pressor test
    Description
    The change in blood pressure will be assessed from quiet rest to sympathetic activation using the cold pressor test
    Time Frame
    Before and after 9 weeks of androgen deprivation therapy or placebo
    Title
    Change in exercise pressor reflex
    Description
    The change in blood pressure will be assessed from quiet rest to isometric handgrip exercise
    Time Frame
    Before and after 9 weeks of androgen deprivation therapy or placebo
    Title
    Change in ambulatory blood pressure variability
    Description
    Ambulatory blood pressure variability will be determined from 24-hour ambulatory blood pressure monitoring.
    Time Frame
    Before and after 9 weeks of androgen deprivation therapy or placebo
    Title
    Change in beat-to-beat blood pressure variability
    Description
    Beat-to-beat blood pressure variability will be using finger photoplethysmography measured in the laboratory.
    Time Frame
    Before and after 9 weeks of androgen deprivation therapy or placebo
    Title
    Change in renal vascular resistance
    Description
    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.
    Time Frame
    Before and after 9 weeks of androgen deprivation therapy or placebo
    Title
    Change in Renal dysfunction biomarkers
    Description
    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.
    Time Frame
    Before and after 9 weeks of androgen deprivation therapy or placebo
    Secondary Outcome Measure Information:
    Title
    Change in sympathetic baroreflex sensitivity
    Description
    Changes in muscle sympathetic nerve activity in response to changes in blood pressure will be assessed using the modified Oxford procedure
    Time Frame
    Before and after 9 weeks of androgen deprivation therapy or placebo
    Title
    Change in Sympathetic reactivity
    Description
    The change in muscle sympathetic nerve activity will be assessed from quiet rest to sympathetic activation using the cold pressor test.
    Time Frame
    Before and after 9 weeks of androgen deprivation therapy or placebo
    Title
    Change in glomerular filtration rate
    Description
    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).
    Time Frame
    Before and after 9 weeks of androgen deprivation therapy or placebo
    Title
    Change in renal plasma flow
    Description
    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).
    Time Frame
    Before and after 9 weeks of androgen deprivation therapy or placebo
    Other Pre-specified Outcome Measures:
    Title
    Change in Inflammation
    Description
    Proteomic analysis of inflammatory cascade proteins will be quantified in plasma samples.
    Time Frame
    Before and after 9 weeks of androgen deprivation therapy or placebo
    Title
    Change in Oxidative stress
    Description
    Whole blood reactive oxygen species will be measured in from venous blood samples using electron paramagnetic resonance spectroscopy
    Time Frame
    Before and after 9 weeks of androgen deprivation therapy or placebo
    Title
    Change in Body composition
    Description
    Descriptive variable total body fat mass (for screening and to document any changes with the intervention)
    Time Frame
    Before and after 9 weeks of androgen deprivation therapy or placebo

    10. Eligibility

    Sex
    Male
    Minimum Age & Unit of Time
    40 Years
    Accepts Healthy Volunteers
    Accepts Healthy Volunteers
    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
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Matthew Babcock, PhD
    Phone
    303-724-1401
    Email
    matthew.babcock@cuanschutz.edu
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Matthew Babcock, PhD
    Organizational Affiliation
    University of Colorado - Anschutz Medical Campus
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Learn more about this trial

    Contributions to Hypertension With Androgen Deprivation Therapy

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