Cardiovascular Outcomes of Low Testosterone (CardioVOLT)
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ClinicalTrials.gov Identifier: NCT02758431 |
Recruitment Status :
Recruiting
First Posted : May 2, 2016
Last Update Posted : April 26, 2022
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Condition or disease | Intervention/treatment | Phase |
---|---|---|
Hypogonadism | Drug: Acyline Drug: Placebo Gel Drug: Placebo Tablet Drug: Testosterone Gel Drug: Arimidex | Not Applicable |
Study Type : | Interventional (Clinical Trial) |
Estimated Enrollment : | 379 participants |
Allocation: | Randomized |
Intervention Model: | Parallel Assignment |
Masking: | Triple (Participant, Investigator, Outcomes Assessor) |
Primary Purpose: | Other |
Official Title: | Cardiovascular Consequences of Hypogonadism in Men |
Study Start Date : | February 2016 |
Estimated Primary Completion Date : | September 2022 |
Estimated Study Completion Date : | November 2022 |

Arm | Intervention/treatment |
---|---|
Placebo Comparator: Group 1: Acyline plus placebo (No Testosterone Add-Back)
Acyline plus placebo gel and placebo tablet.
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Drug: Acyline
Acyline 300ug/kg injection will be administered on Day 0 and on day 14
Other Name: Gonadotropin releasing hormone antagonist Drug: Placebo Gel Placebo gel packet applied daily for 28 days.
Other Name: Placebo Drug: Placebo Tablet Placebo oral tablet taken daily for 28 days.
Other Name: Placebo |
Active Comparator: Group 2: Acyline plusTestosterone
Acyline plus transdermal testosterone gel plus placebo tablet.
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Drug: Acyline
Acyline 300ug/kg injection will be administered on Day 0 and on day 14
Other Name: Gonadotropin releasing hormone antagonist Drug: Placebo Tablet Placebo oral tablet taken daily for 28 days.
Other Name: Placebo Drug: Testosterone Gel Testosterone Gel applied daily for 28 days
Other Name: Transdermal Testosterone Gel |
Active Comparator: Group 3: Acyline plus Testosterone plus Arimidex)
Acyline plus transdermal testosterone gel plus Aromatase inhibitor (Arimidex) oral.
|
Drug: Acyline
Acyline 300ug/kg injection will be administered on Day 0 and on day 14
Other Name: Gonadotropin releasing hormone antagonist Drug: Testosterone Gel Testosterone Gel applied daily for 28 days
Other Name: Transdermal Testosterone Gel Drug: Arimidex Arimidex Oral Tablet 1mg taken orally daily for 28 days
Other Name: Aromatase inhibitor |
- Endothelial function [ Time Frame: Change from baseline at 28 days ]Brachial artery flow-mediated dilation, and EndoPAT™
- Carotid artery compliance [ Time Frame: Change from baseline at 28 days ]Carotid artery compliance and beta stiffness index
- Arterial stiffness [ Time Frame: Change from baseline at 28 days ]Pulse-wave velocity
- Left ventricular diastolic function [ Time Frame: Change from baseline at 28 days ]Measured via Cardiac Echo
- NADPH oxidase [ Time Frame: Change from baseline at 28 days ]Oxidative stress marker measured in endothelial cells
- Nitrotyrosine [ Time Frame: Change from baseline at 28 days ]Measured in endothelial cells
- MnSOD [ Time Frame: Change from baseline at 28 days ]Mitochondrial superoxide dismutase measured in endothelial cells
- eNOS [ Time Frame: Change from baseline at 28 days ]Endothelial nitric oxide synthase (eNOS) measured in endothelial cell
- COX IV [ Time Frame: Change from baseline at 28 days ]Marker of mitochondrial function measured in PBMCs
- Mitochondrial RCR [ Time Frame: Change from baseline at 28 days ]Mitochondrial respiration measured via Oroboros O2K
- Supine blood pressure [ Time Frame: Change from baseline at 28 days ]On the cardiovascular testing days, supine blood pressure will be measured in triplicate.
- Body Composition [ Time Frame: Baseline ]Whole body and regional body composition will be determined using dual energy x-ray absorptiometry for subject characteristics and for the determination of fat-free mass for the AA dose preparation.
- Plasma Lipid Concentrations [ Time Frame: Baseline ]Plasma lipid concentrations, including total-cholesterol (C) and triglycerides (TG) will be determined at baseline. The rationale for making these measurements is for screening criteria, subject characteristics, and because they may correlate with CV function.
- Glucose Concentrations [ Time Frame: Change from baseline at 28 days ]Fasted glucose concentrations will be measured at screening and at each vascular test.
- Sex Hormones [ Time Frame: Change from baseline at 28 days ]Serum concentrations of total testosterone (T), estradiol, albumin, sex hormone binding globulin (SHBG), luteinizing hormone and follicle stimulating hormone will be measured to document changes in hormone concentrations and free T will be calculated using the known affinity constants of T for SHBG and for albumin. Additional measures of T will be measured after 60 days if testosterone has not returned to baseline. The 60 day plus measures are for safety.
- Endothelin-1 (ET-1) [ Time Frame: Change from baseline at 28 days ]Plasma ET-1 will be measured because it is a potent vasoconstrictor and has complex interactions with NO. Specifically, ET-1 synthesis is under tonic inhibition by NO.
- Physical Activity Levels [ Time Frame: Change from baseline at 28 days ]To document the habitual physical activity status at baseline and the last week of respective interventions, daily energy expenditure will be estimated using ActivPal monitors.

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Ages Eligible for Study: | 18 Years to 75 Years (Adult, Older Adult) |
Sexes Eligible for Study: | Male |
Accepts Healthy Volunteers: | Yes |
Inclusion Criteria:
- 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.
Exclusion Criteria:
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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).

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02758431
Contact: Kerrie Moreau, PhD | 303-724-1914 | kerrie.moreau@ucdenver.edu |
United States, Colorado | |
University of Colorado CCTSI CTRC | Recruiting |
Denver, Colorado, United States, 80045 | |
Contact: Kerrie Moreau, PhD 303-724-1914 kerrie.moreau@ucdenver.edu |
Principal Investigator: | Kerrie Moreau, PhD | University of Colorado, Denver |
Responsible Party: | University of Colorado, Denver |
ClinicalTrials.gov Identifier: | NCT02758431 |
Other Study ID Numbers: |
15-1162 UL1TR001082 ( U.S. NIH Grant/Contract ) |
First Posted: | May 2, 2016 Key Record Dates |
Last Update Posted: | April 26, 2022 |
Last Verified: | April 2022 |
Individual Participant Data (IPD) Sharing Statement: | |
Plan to Share IPD: | No |
testosterone |
Hypogonadism Gonadal Disorders Endocrine System Diseases Methyltestosterone Anastrozole Testosterone Testosterone undecanoate Testosterone enanthate Testosterone 17 beta-cypionate Aromatase Inhibitors Acyline Hormone Antagonists |
Hormones Hormones, Hormone Substitutes, and Hormone Antagonists Physiological Effects of Drugs Androgens Antineoplastic Agents, Hormonal Antineoplastic Agents Anabolic Agents Steroid Synthesis Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Estrogen Antagonists |