- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02758431
Cardiovascular Outcomes of Low Testosterone (CardioVOLT)
Cardiovascular Consequences of Hypogonadism in Men
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Estimated)
Phase
- Not Applicable
Contacts and Locations
Study Locations
-
-
Colorado
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Denver, Colorado, United States, 80045
- University of Colorado CCTSI CTRC
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
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:
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).
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Other
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Triple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Placebo Comparator: Group 1: Acyline plus placebo (No Testosterone Add-Back)
Acyline plus placebo gel and placebo tablet.
|
Acyline 300ug/kg injection will be administered on Day 0 and on day 14
Other Names:
Placebo gel packet applied daily for 28 days.
Other Names:
Placebo oral tablet taken daily for 28 days.
Other Names:
|
Active Comparator: Group 2: Acyline plusTestosterone
Acyline plus transdermal testosterone gel plus placebo tablet.
|
Acyline 300ug/kg injection will be administered on Day 0 and on day 14
Other Names:
Placebo oral tablet taken daily for 28 days.
Other Names:
Testosterone Gel applied daily for 28 days
Other Names:
|
Active Comparator: Group 3: Acyline plus Testosterone plus Arimidex)
Acyline plus transdermal testosterone gel plus Aromatase inhibitor (Arimidex) oral.
|
Acyline 300ug/kg injection will be administered on Day 0 and on day 14
Other Names:
Testosterone Gel applied daily for 28 days
Other Names:
Arimidex Oral Tablet 1mg taken orally daily for 28 days
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Endothelial function
Time Frame: Change from baseline at 28 days
|
Brachial artery flow-mediated dilation, and EndoPAT™
|
Change from baseline at 28 days
|
Carotid artery compliance
Time Frame: Change from baseline at 28 days
|
Carotid artery compliance and beta stiffness index
|
Change from baseline at 28 days
|
Arterial stiffness
Time Frame: Change from baseline at 28 days
|
Pulse-wave velocity
|
Change from baseline at 28 days
|
Left ventricular diastolic function
Time Frame: Change from baseline at 28 days
|
Measured via Cardiac Echo
|
Change from baseline at 28 days
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
NADPH oxidase
Time Frame: Change from baseline at 28 days
|
Oxidative stress marker measured in endothelial cells
|
Change from baseline at 28 days
|
Nitrotyrosine
Time Frame: Change from baseline at 28 days
|
Measured in endothelial cells
|
Change from baseline at 28 days
|
MnSOD
Time Frame: Change from baseline at 28 days
|
Mitochondrial superoxide dismutase measured in endothelial cells
|
Change from baseline at 28 days
|
eNOS
Time Frame: Change from baseline at 28 days
|
Endothelial nitric oxide synthase (eNOS) measured in endothelial cell
|
Change from baseline at 28 days
|
COX IV
Time Frame: Change from baseline at 28 days
|
Marker of mitochondrial function measured in PBMCs
|
Change from baseline at 28 days
|
Mitochondrial RCR
Time Frame: Change from baseline at 28 days
|
Mitochondrial respiration measured via Oroboros O2K
|
Change from baseline at 28 days
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Supine blood pressure
Time Frame: Change from baseline at 28 days
|
On the cardiovascular testing days, supine blood pressure will be measured in triplicate.
|
Change from baseline at 28 days
|
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.
|
Baseline
|
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.
|
Baseline
|
Glucose Concentrations
Time Frame: Change from baseline at 28 days
|
Fasted glucose concentrations will be measured at screening and at each vascular test.
|
Change from baseline at 28 days
|
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.
|
Change from baseline at 28 days
|
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.
|
Change from baseline at 28 days
|
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.
|
Change from baseline at 28 days
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Kerrie Moreau, PhD, University of Colorado, Denver
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimated)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Endocrine System Diseases
- Gonadal Disorders
- Hypogonadism
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antineoplastic Agents
- Hormones
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Antineoplastic Agents, Hormonal
- Steroid Synthesis Inhibitors
- Estrogen Antagonists
- Androgens
- Anabolic Agents
- Testosterone
- Anastrozole
- Aromatase Inhibitors
- Methyltestosterone
- Testosterone undecanoate
- Testosterone enanthate
- Testosterone 17 beta-cypionate
- Acyline
- Hormone Antagonists
Other Study ID Numbers
- 15-1162
- R01AG049762 (U.S. NIH Grant/Contract)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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