HypogonadismCardioVOLTNCT02758431
Cardiovascular Outcomes of Low Testosterone
A study testing Acyline, Testosterone Gel and Arimidex in people with Hypogonadism, run by University of Colorado, Denver at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Hypogonadism
- What is being tested?
- Acyline, Testosterone Gel and Arimidex
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 232 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Jul 2016to 4 Jan 2023
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- Men only
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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
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- 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.
Who cannot join
- 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
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- 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).
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Colorado CCTSI CTRC
Denver, Colorado, 80045
About this study
Official title: Cardiovascular Consequences of Hypogonadism in Men
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.
Read the detailed description
Cardiovascular (CV) aging, featuring large artery stiffening, endothelial dysfunction, and impaired left ventricular (LV) diastolic function, is a major risk factor for the development of cardiovascular diseases (CVD). Male aging is associated with a gradual and variable decline in serum testosterone (T) and low T is associated with accelerated CV aging. The purpose of this research is to determine the key functional mechanisms underlying accelerated CV aging in older men with low T. The overall hypothesis is that mitochondrial dysfunction and oxidative stress are mechanisms underlying the apparent accelerated CV aging in older men with low T. To test this hypothesis Aim 1 will use cross-sectional comparisons of young and older men with normal T (≥400 ng/dl), and older men with chronically low T (<300 ng/dl). To better isolate the effects of low T from factors that change with aging and chronic low T, Aim 2 will expand on the cross-sectional comparisons by assessing measures of CV function, oxidative stress burden and mitochondrial function in older men with normal T before and after randomization to short-term (28 d) gonadal suppression (gonadotropin releasing hormone antagonist, GnRHant) + placebo (PL), GnRHant+T alone, or GnRHant+T+aromatase inhibitor (AI). AI will control for the effects of aromatization of T to estradiol (E2), and thereby isolate T effects while suppressing E2, a potent modulator of CV function. The results from this research should provide new mechanistic insight into the processes that mediate the impairment in CV function at the cellular and systemic level in older men with low T. These studies will lead to a better understanding of the independent role of T in age-related changes in CV function and the mechanisms of action, which will help guide future sex-specific therapies for the prevention of CVD.
- Conditions
- Hypogonadism
- Being tested
- Acyline, Placebo Gel, Placebo Tablet, Testosterone Gel, Arimidex
- Keywords
- testosterone
- Medical subject headings
- Hypogonadism
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AcylineDrug
Also called Gonadotropin releasing hormone antagonist
Acyline 300ug/kg injection will be administered on Day 0 and on day 14
Placebo GelDrug
Also called Placebo
Placebo gel packet applied daily for 28 days.
Placebo TabletDrug
Also called Placebo
Placebo oral tablet taken daily for 28 days.
Testosterone GelDrug
Also called Transdermal Testosterone Gel
Testosterone Gel applied daily for 28 days
ArimidexDrug
Also called Aromatase inhibitor
Arimidex Oral Tablet 1mg taken orally daily for 28 days
| Study group | Role | What they receive |
|---|---|---|
| Group 1: Acyline plus placebo (No Testosterone Add-Back) | Placebo comparator | Acyline plus placebo gel and placebo tablet. Receives: Drug: Acyline; Drug: Placebo Gel; Drug: Placebo Tablet |
| Group 2: Acyline plusTestosterone | Active comparator | Acyline plus transdermal testosterone gel plus placebo tablet. Receives: 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. Receives: Drug: Acyline; Drug: Testosterone Gel; Drug: Arimidex |
What is being measured
The primary outcome is the main question the study is designed to answer.
Endothelial function
Brachial artery flow-mediated dilation, and EndoPAT™
Measured: Change from baseline at 28 days
Carotid artery compliance
Carotid artery compliance and beta stiffness index
Measured: Change from baseline at 28 days
Arterial stiffness
Pulse-wave velocity
Measured: Change from baseline at 28 days
Left ventricular diastolic function
Measured via Cardiac Echo
Measured: Change from baseline at 28 days
Secondary outcomes (6)
NADPH oxidase
Oxidative stress marker measured in endothelial cells
Measured: Change from baseline at 28 days
Nitrotyrosine
Measured in endothelial cells
Measured: Change from baseline at 28 days
MnSOD
Mitochondrial superoxide dismutase measured in endothelial cells
Measured: Change from baseline at 28 days
eNOS
Endothelial nitric oxide synthase (eNOS) measured in endothelial cell
Measured: Change from baseline at 28 days
COX IV
Marker of mitochondrial function measured in PBMCs
Measured: Change from baseline at 28 days
Mitochondrial RCR
Mitochondrial respiration measured via Oroboros O2K
Measured: Change from baseline at 28 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 May 2016 (estimated)
- Study start1 Jul 2016
- Primary completion4 Jan 2023
- Study completion4 Jan 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HypogonadismStudies of the same condition, open and under way.
- More trials run by University of Colorado, DenverThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 232 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Colorado, Denver
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute on Aging (NIA)
- Responsible party
- Sponsor
- Investigators
- Kerrie Moreau, PhD, Principal investigator, University of Colorado, Denver
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02758431
- Sponsor's protocol ID
- 15-1162
- Other IDs
- R01AG049762
- Acronym
- CardioVOLT
- Status last verified
- Oct 2024
- First submitted
- 20 Apr 2016
- Last updated
- 10 Oct 2024
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Cardiovascular Consequences of Hypogonadism in Men
- ClinicalTrials.gov ID
- NCT02758431
- Acronym / sponsor ID
- CardioVOLT / 15-1162
- Conditions
- Hypogonadism
- Keywords
- testosterone
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 232 participants (actual)
- Lead sponsor
- University of Colorado, DenverUniversity, hospital or other
- Collaborators
- National Institute on Aging (NIA)
- Study start
- 1 Jul 2016 (actual)
- Primary completion
- 4 Jan 2023 (actual)
- Study completion
- 4 Jan 2023 (actual)
- First posted
- 2 May 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Cardiovascular (CV) aging, featuring large artery stiffening, endothelial dysfunction, and impaired left ventricular (LV) diastolic function, is a major risk factor for the development of cardiovascular diseases (CVD). Male aging is associated with a gradual and variable decline in serum testosterone (T) and low T is associated with accelerated CV aging. The purpose of this research is to determine the key functional mechanisms underlying accelerated CV aging in older men with low T. The overall hypothesis is that mitochondrial dysfunction and oxidative stress are mechanisms underlying the apparent accelerated CV aging in older men with low T. To test this hypothesis Aim 1 will use cross-sectional comparisons of young and older men with normal T (≥400 ng/dl), and older men with chronically low T (<300 ng/dl). To better isolate the effects of low T from factors that change with aging and chronic low T, Aim 2 will expand on the cross-sectional comparisons by assessing measures of CV function, oxidative stress burden and mitochondrial function in older men with normal T before and after randomization to short-term (28 d) gonadal suppression (gonadotropin releasing hormone antagonist, GnRHant) + placebo (PL), GnRHant+T alone, or GnRHant+T+aromatase inhibitor (AI). AI will control for the effects of aromatization of T to estradiol (E2), and thereby isolate T effects while suppressing E2, a potent modulator of CV function. The results from this research should provide new mechanistic insight into the processes that mediate the impairment in CV function at the cellular and systemic level in older men with low T. These studies will lead to a better understanding of the independent role of T in age-related changes in CV function and the mechanisms of action, which will help guide future sex-specific therapies for the prevention of CVD.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Group 1: Acyline plus placebo (No Testosterone Add-Back) | Placebo comparator | Drug: Acyline, Drug: Placebo Gel, Drug: Placebo TabletAcyline plus placebo gel and placebo tablet. |
| Group 2: Acyline plusTestosterone | Active comparator | Drug: Acyline, Drug: Placebo Tablet, Drug: Testosterone GelAcyline plus transdermal testosterone gel plus placebo tablet. |
| Group 3: Acyline plus Testosterone plus Arimidex) | Active comparator | Drug: Acyline, Drug: Testosterone Gel, Drug: ArimidexAcyline plus transdermal testosterone gel plus Aromatase inhibitor (Arimidex) oral. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- 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
Key exclusion criteria (13 listed)
- Contraindications to:
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AcylineAlso: Gonadotropin releasing hormone antagonistAcyline 300ug/kg injection will be administered on Day 0 and on day 14 | Drug | Group 1: Acyline plus placebo (No Testosterone Add-Back), Group 2: Acyline plusTestosterone, Group 3: Acyline plus Testosterone plus Arimidex) |
| Placebo GelAlso: PlaceboPlacebo gel packet applied daily for 28 days. | Drug | Group 1: Acyline plus placebo (No Testosterone Add-Back) |
| Placebo TabletAlso: PlaceboPlacebo oral tablet taken daily for 28 days. | Drug | Group 1: Acyline plus placebo (No Testosterone Add-Back), Group 2: Acyline plusTestosterone |
| Testosterone GelAlso: Transdermal Testosterone GelTestosterone Gel applied daily for 28 days | Drug | Group 2: Acyline plusTestosterone, Group 3: Acyline plus Testosterone plus Arimidex) |
| ArimidexAlso: Aromatase inhibitorArimidex Oral Tablet 1mg taken orally daily for 28 days | Drug | Group 3: Acyline plus Testosterone plus Arimidex) |
Primary outcome
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
6 secondary outcomes
NADPH oxidase
Time frame: Change from baseline at 28 days
Nitrotyrosine
Time frame: Change from baseline at 28 days
MnSOD
Time frame: Change from baseline at 28 days
eNOS
Time frame: Change from baseline at 28 days
COX IV
Time frame: Change from baseline at 28 days
Mitochondrial RCR
Time frame: Change from baseline at 28 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Oct 2024.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Kerrie Moreau, PhD principal investigator
University of Colorado, Denver
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Acyline, Testosterone Gel and Arimidex in people with Hypogonadism, run by University of Colorado, Denver at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 10 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Endothelial function (time frame: Change from baseline at 28 days). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Oct 2024.