Cardiovascular Outcomes of Low Testosterone

NCT02758431 | Completed

• 2 other identifiers: 15-1162R01AG049762
• Study Type: interventional
• Target: 232
• Locations: 1 country
• Sites: 1

Brief Summary

This study plans to learn more about heart and vascular aging in men. In some men as they get older, testosterone levels fall below the normal range for young men. Also, as men get older cardiovascular health worsens. This can lead to high blood pressure and heart disease. In this study we want to find out what causes cardiovascular health to worsen in older men. Also we want to find out what happens when testosterone levels are lowered for a short time. Specifically, we want to see if the reduction in cardiovascular health in older men with low testosterone levels is because of damage to mitochondria. Mitochondria are the main power supply of the cells in our body. The results from this study will help to understand why cardiovascular health declines in older men with low testosterone levels compared to younger men and older men who have higher testosterone levels. Knowing this information will help to develop therapies to prevent heart disease in men.

Conditions

Hypogonadism

Keywords

testosterone

Outcome Measures

Primary Outcomes (4)

• Endothelial function

  Brachial artery flow-mediated dilation, and EndoPAT™

  Change from baseline at 28 days

• Carotid artery compliance

  Carotid artery compliance and beta stiffness index

  Change from baseline at 28 days

• Arterial stiffness

  Pulse-wave velocity

  Change from baseline at 28 days

• Left ventricular diastolic function

  Measured via Cardiac Echo

  Change from baseline at 28 days

Secondary Outcomes (6)

• NADPH oxidase

  Change from baseline at 28 days

• Nitrotyrosine

  Change from baseline at 28 days

• MnSOD

  Change from baseline at 28 days

• eNOS

  Change from baseline at 28 days

• COX IV

  Change from baseline at 28 days

Other Outcomes (7)

• Supine blood pressure

  Change from baseline at 28 days

• Body Composition

  Baseline

• Plasma Lipid Concentrations

  Baseline

Study Arms (3)

Group 1: Acyline plus placebo (No Testosterone Add-Back)

PLACEBO COMPARATOR

Acyline plus placebo gel and placebo tablet.

Drug: Acyline; Drug: Placebo Gel; Drug: Placebo Tablet

Group 2: Acyline plusTestosterone

ACTIVE COMPARATOR

Acyline plus transdermal testosterone gel plus placebo tablet.

Drug: Acyline; Drug: Placebo Tablet; Drug: Testosterone Gel

Group 3: Acyline plus Testosterone plus Arimidex)

ACTIVE COMPARATOR

Acyline plus transdermal testosterone gel plus Aromatase inhibitor (Arimidex) oral.

Drug: Acyline; Drug: Testosterone Gel; Drug: Arimidex

Interventions

Acyline DRUG

Acyline 300ug/kg injection will be administered on Day 0 and on day 14

Also known as: Gonadotropin releasing hormone antagonist

Group 1: Acyline plus placebo (No Testosterone Add-Back); Group 2: Acyline plusTestosterone; Group 3: Acyline plus Testosterone plus Arimidex)

Placebo Gel DRUG

Placebo gel packet applied daily for 28 days.

Also known as: Placebo

Group 1: Acyline plus placebo (No Testosterone Add-Back)

Placebo Tablet DRUG

Placebo oral tablet taken daily for 28 days.

Also known as: Placebo

Group 1: Acyline plus placebo (No Testosterone Add-Back); Group 2: Acyline plusTestosterone

Testosterone Gel DRUG

Testosterone Gel applied daily for 28 days

Also known as: Transdermal Testosterone Gel

Group 2: Acyline plusTestosterone; Group 3: Acyline plus Testosterone plus Arimidex)

Arimidex DRUG

Arimidex Oral Tablet 1mg taken orally daily for 28 days

Also known as: Aromatase inhibitor

Group 3: Acyline plus Testosterone plus Arimidex)

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Men aged 18-40 years and 50-75 years
• Chronically low testosterone group will have testosterone concentrations \<300 ng/dl, and young and older normal testosterone groups will have testosterone levels 400-1000 ng/dl
• No use of sex hormones for at least 1 year
• Body mass index \<40 kg/m2
• Nonsmokers
• Resting blood pressure \<160/90 mmHg
• Fasting plasma glucose \<126 mg/dL
• Healthy, as determined by medical history, physical examination, standard blood chemistries (chemistry panel, complete blood clot and circulating thyroid levels) and a graded exercise stress test with monitoring of blood pressure and electrocardiogram (ECG)
• Sedentary or recreationally active (\< 3 days/wk of vigorous aerobic exercise)
• No use of medications that might influence cardiovascular function including anti-hypertensive, lipid lowering medications, and corticosteroids
• No use of vitamin supplements or anti-inflammatory medications, or willing to stop 1 month prior and throughout the study.

You may not qualify if:

• Contraindications to:
• Gonadotropin releasing hormone (GnRH) antagonist
• Testosterone gel and aromatase inhibitor including hypersensitivity to Acyline, Androgel®, Arimidex®
• Extrinsic peptide hormones, mannitol, GnRH or any other GnRH analogs
• History of or active prostate or breast cancer or other sex hormone-dependent neoplasms
• Pre-existing or active cardiac, renal or hepatic disease
• History of stomach ulcer or bleeding
• History of epilepsy or other seizure disorder
• Diabetes
• Active infection
• Disease that affects the nervous system
• Abnormal resting ECG
• Additionally, men participating in the gonadal suppression intervention study will do so with the understanding that they will be randomly assigned to study groups that involve either GnRH antagonist plus testosterone gel plus placebo tablet (33% chance), GnRH antagonist plus testosterone gel plus aromatase inhibitor tablet (33% chance) or GnRH antagonist plus placebo gel plus placebo tablet (33% chance).

Sponsors & Collaborators

• University of Colorado, Denver: lead
• National Institute on Aging (NIA): collaborator

Study Sites (1)

University of Colorado CCTSI CTRC

Denver, Colorado, 80045, United States

Location

MeSH Terms

Conditions

Hypogonadism

Interventions

acyline; Anastrozole; Aromatase Inhibitors

Condition Hierarchy (Ancestors)

Gonadal Disorders; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Nitriles; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Steroid Synthesis Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Estrogen Antagonists; Hormone Antagonists; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs

Study Officials

• Kerrie Moreau, PhD

  University of Colorado, Denver

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 20, 2016
• First Posted: May 2, 2016
• Study Start: July 1, 2016
• Primary Completion: January 4, 2023
• Study Completion: January 4, 2023
• Last Updated: October 10, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)