Transgender MenNCT04524325
Mechanisms of Blood Pressure Dysfunction in Transmen Receiving Testosterone
A study testing Trans men in people with Transgender Men and Blood Pressure, run by Yale University.
Trial summary
The purpose of this research is to explore the effects of chronic androgen exposure on sympathetic nervous system activity (SNSA) and baroreflex control of blood pressure responses in transgender men (trans men) taking gender affirming hormone therapy (HT). Read more about this study
- Who is it for?
- Ages 18 to 45 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Transgender Men, Blood Pressure, Hyperandrogenism
- What is being tested?
- Trans men
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- 1 Jan 2023to 30 Jun 2024
- 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 45 years
- Women only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Both groups (trans men and cisgender women) must be healthy and non-smoking. Control participants must be cisgender women with regular menses every 26-34 days. Trans men participants must be currently receiving testosterone for gender affirming hormone therapy where physiologic doses of exogenous Dihydrotestosterone have been administered (via injection or transdermal application) for at least 3 months as prescribed by their local endocrine provider as part of their clinically indicated hormone therapy. Doses can vary depending on the size and goals of each patient, but blood testosterone will be between 400-1000 ng/dl.
Who cannot join
- Subjects who smoke, have diabetes, or BP>140/90 will be excluded.
- Subjects will not be taking medications during the study, including any insulin-sensitizing or cardiovascular medications.
- Subjects are excluded if they have lost > 5 kg of weight within the past 6 months or perform high-intensity exercise > 3 times/week.
About this study
The purpose of this research is to explore the effects of chronic androgen exposure on sympathetic nervous system activity (SNSA) and baroreflex control of blood pressure responses in transgender men (trans men) taking gender affirming hormone therapy (HT). Blood pressure, baroreflex gain, and frequency of sympathetic responses to changes in blood pressure will be assessed in trans men and a control group of cisgender women. To fully understand HT effects on blood pressure regulation in trans men, it is crucial to understand how both SNSA, and the pattern of SNSA, can be influenced by high levels of androgen exposure in the female cardiovascular system, as well as how the two regulatory components may interact.
Read the detailed description
The purpose of this research is to study how testosterone affects blood pressure control in trans men. High testosterone levels are detrimental to the female cardiovascular system in that higher levels are associated with increased blood pressure. Humans control blood pressure in the autonomic nervous system via the baroreflex mechanism. The arterial baroreflex is a key autonomic homeostatic mechanism involved in maintaining arterial blood pressure, and gain of the baroreflex is used as a measure of the sensitivity of sympathetic responses that act to restore acute blood pressure fluctuations. This autonomic regulation of blood pressure is also characterized by rhythmic activity (changes in cardiac frequency), which can be observed by recording sympathetic nerve traffic. When the female cardiovascular system is exposed to elevated androgens, baroreflex gain is impaired, and blood control is less efficient during an orthostatic challenge. However, to best understand the effect of a given stimulus on autonomic function, changes in frequency of the SNSA response must also be quantified in addition to the gain. Sympathetic control of arterial blood pressure is most effective in a narrow frequency range, and if this frequency range for responsiveness should narrow further, control of arterial blood pressure becomes less efficient and presents as dysfunction. The central hypothesis for this research is that dysregulation of blood pressure in trans men taking testosterone for gender affirming HT is a function of both reduced baroreflex gain and narrowed frequency-dependent relationship between arterial pressure and peripheral sympathetic vascular responsiveness. Specifically, these studies test the hypothesis that androgen supplementation with HT is associated with 1) lower baroreflex gain during a lower body negative pressure (LBNP) challenge, and 2) a narrowed response frequency range that precedes impaired sympathetic vascular response dynamics in trans men compared to control cisgender women.
Study procedures include an oral glucose tolerance test (OGTT), microneurography of the median nerve in the forearm to assess SNSA, and 2 LBNP challenges designed to examine baroreflex gain during static LBNP and then the frequency of SNSA during oscillating LBNP (OLBNP). Participants complete 3 visits for this study. Visit 1 is for informed consent procedures; Visit 2 is a pre-screening visit to complete the OGTT; Visit 3 is for experimental testing to assess gain and the frequency range. Blood pressure, heart rate and muscle SNSA (MSNA) are measured during LBNP and OLBNP. MSNA is recorded using 2 microelectrodes inserted through the skin of the forearm to record activity (firing) of the median nerve. Blood samples are taken via IV placement to measure insulin and glucose during the OGTT for Visit 2, and then sex hormones and catecholamines during Visit 3. Results from the group of young trans men will be compared to a control group of cisgender women matched for age and body mass index.
- Conditions
- Transgender Men, Blood Pressure, Hyperandrogenism
- Being tested
- Trans men
- Keywords
- transgender, baroreflex, testosterone
- Medical subject headings
- Hyperandrogenism
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Trans menOther
We are studying the effects of testosterone taken by trans men on mechanisms of blood pressure control and comparing those results to cisgender women that have normal (ie lower) testosterone levels.
| Study group | Role | What they receive |
|---|---|---|
| Trans men | Active comparator | transgender men taking physiologic doses of testosterone for gender affirming hormone therapy Receives: Other: Trans men |
| control | No intervention | cisgender women not receiving testosterone and with normal sex hormone levels |
What is being measured
The primary outcome is the main question the study is designed to answer.
Muscle Sympathetic Nerve Activity (MSNA)
MSNA is recorded continuously at rest and during O/LBNP protocols with a tungsten microelectrode (0.2 diameters insulated shaft tapered to an uninsulated tip of ~1-5 μm) inserted percutaneously into the median nerve. Multiunit, postganglionic MSNA is distinguished from other sources of nerve activity by the presence of spontaneous pulse synchronous bursts, increased activity when the subject holds their breath or clenches their first (stretches forearm muscles around median nerve), or if activity does not change when the skin is stimulated by light brushing or stroking (indicates lack of skin nerve activity). Bursts of MSNA at rest and during LBNP are quantified as total activity (AU/min), burst frequency (bursts/min) and burst incidence (bursts/100 heartbeats). The MSNA burst incidence is expressed in bursts/100 heartbeats to normalize for differences in heart rate among subjects.
Measured: 3 hours
Systolic Blood Pressure (SBP)
SBP is measured continuously with a Finometer beat-to-beat blood pressure measurement system at rest and during O/LBNP protocols. Units are mm Hg.
Measured: 3 hours
Diastolic Blood Pressure (DBP)
DBP is measured continuously with a Finometer beat-to-beat blood pressure measurement system at rest and during O/LBNP protocols. Units are mm Hg.
Measured: 3 hours
Mean Arterial Pressure (MAP)
MAP at rest and during O/LBNP protocols is calculated as 1/3(SBP-DBP)+DBP using the beat-to-beat SBP and DBP measurements taken with the Finometer system. Units are mm Hg.
Measured: 3 hours
Sympathetic Baroreflex (BR) Gain
Sympathetic BR gain is used as an index of sympathetic (neural) control of blood pressure, where gain is determined by the slope of the linear relationship between MSNA (burst/100 heartbeats) and DBP (mm Hg) at rest and during LBNP. The relationship produces a negative slope in that for a given subject, when DBP falls below the normal level sustained at rest, sympathetic activity increases to restore DBP back to that normal level. Thus, more MSNA bursts are observed at lower levels of DBP and vice versa. A steeper (more negative) slope suggests greater sensitivity of the baroreceptors to changes in blood pressure, and thereby more effective sympathetic control of blood pressure. A flatter slope suggests impaired BR sensitivity and blood pressure dysfunction, which is expected for the trans men group compared to cisgender women controls.
Measured: 3 hours
Frequency in the Neural Cardiovascular Control
The frequency of SBP, DBP and heart rate during OLBNP is analyzed in Matlab in a linear time-invariant system (LTI) framework. Heart rate and BP measures taken during OLBNP are low-pass filtered (0.05 Hz estimated example) and corrected for end-effects using a Hamming window. The derived impulse responses (IRs) are 1/3rd octave smoothed before calculating the frequency power spectra (0.001-0.05 Hz estimated example). The power of DBP and SBP at the OLBNP frequency are anticipated to be independently inversely related to the efficiency of BP control. Further, the difference in heart rate and SBP, and in heart rate and DBP, power at those frequencies reflects the degree of autonomic function, analogous to baroreflex gain.
Measured: 0.5 hours
Electrocardiogram (ECG)
A 3-lead ECG is continuously recorded at rest and during the O/LBNP protocols. The R-wave of the QRS complex of the ECG recording will be used for measures of pulse interval by determining the amount of time in seconds between the R-waves of 2 consecutive QRS complexes.
Measured: 3 hours
Secondary outcomes (2)
Brachial Artery Mean Blood Flow Velocity
Mean blood flow velocity in the brachial artery will be examined at rest and during LBNP using Doppler ultrasound velocimetry. Blood flow velocity spectra and arterial diameter are measured simultaneously with a Doppler probe and SonoScape S2 ultrasound system. The brachial artery is imaged with a 6.0-MHz linear array probe positioned at a 45° angle over the skin at the distal one-third of the upper arm. Brachial blood flow is expected to decrease as the level of LBNP increases and induces a greater orthostatic challenge. For example, blood flow would be highest at the -10LBNP stage and continually decrease during the following stages of -20, -30 and finally -40LBNP, where blood flow would be the lowest.
Measured: 3 hours
Cardiovagal Baroreflex (BR) Gain
Cardiovagal BR gain is determined by the slope of the linear relationship between R-R Interval (seconds) and SBP (mm Hg) at rest and during LBNP. R-R Intervals are obtained from the ECG recording and SBP is obtained from the beat-to-beat measures taken by the Finometer.
Measured: 3 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Aug 2020
- Study start1 Jan 2023 (estimated)
- Primary completion1 Jul 2023 (estimated)
- Study completion30 Jun 2024 (estimated)
Why it stopped: Funding never received.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Transgender MenStudies of the same condition, open and under way.
- More trials run by Yale UniversityThe 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
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- There is 1 group of trans men (n=20) and 1 group of cisgender women (n=20). Study procedures, protocols, and measurements will be the same for both groups and performed and/or taken in a similar time period.
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Yale University
- Sponsor type
- University, hospital or other
- Collaborators
- The John B. Pierce Laboratory
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04524325
- Sponsor's protocol ID
- 2000027735
- Status last verified
- Oct 2022
- First submitted
- 17 Aug 2020
- Last updated
- 3 Nov 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 3 Nov 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Mechanisms of Blood Pressure Dysfunction in Transmen Receiving Testosterone
- ClinicalTrials.gov ID
- NCT04524325
- Acronym / sponsor ID
- 2000027735
- Conditions
- Transgender Men, Blood Pressure, Hyperandrogenism
- Keywords
- transgender, baroreflex, testosterone
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Funding never received.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Yale UniversityUniversity, hospital or other
- Collaborators
- The John B. Pierce Laboratory
- Study start
- 1 Jan 2023 (estimated)
- Primary completion
- 1 Jul 2023 (estimated)
- Study completion
- 30 Jun 2024 (estimated)
- First posted
- 24 Aug 2020 (actual)
- 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.
The purpose of this research is to explore the effects of chronic androgen exposure on sympathetic nervous system activity (SNSA) and baroreflex control of blood pressure responses in transgender men (trans men) taking gender affirming hormone therapy (HT). Blood pressure, baroreflex gain, and frequency of sympathetic responses to changes in blood pressure will be assessed in trans men and a control group of cisgender women. To fully understand HT effects on blood pressure regulation in trans men, it is crucial to understand how both SNSA, and the pattern of SNSA, can be influenced by high levels of androgen exposure in the female cardiovascular system, as well as how the two regulatory components may interact.
Detailed description
The purpose of this research is to study how testosterone affects blood pressure control in trans men. High testosterone levels are detrimental to the female cardiovascular system in that higher levels are associated with increased blood pressure. Humans control blood pressure in the autonomic nervous system via the baroreflex mechanism. The arterial baroreflex is a key autonomic homeostatic mechanism involved in maintaining arterial blood pressure, and gain of the baroreflex is used as a measure of the sensitivity of sympathetic responses that act to restore acute blood pressure fluctuations. This autonomic regulation of blood pressure is also characterized by rhythmic activity (changes in cardiac frequency), which can be observed by recording sympathetic nerve traffic. When the female cardiovascular system is exposed to elevated androgens, baroreflex gain is impaired, and blood control is less efficient during an orthostatic challenge. However, to best understand the effect of a given stimulus on autonomic function, changes in frequency of the SNSA response must also be quantified in addition to the gain. Sympathetic control of arterial blood pressure is most effective in a narrow frequency range, and if this frequency range for responsiveness should narrow further, control of arterial blood pressure becomes less efficient and presents as dysfunction. The central hypothesis for this research is that dysregulation of blood pressure in trans men taking testosterone for gender affirming HT is a function of both reduced baroreflex gain and narrowed frequency-dependent relationship between arterial pressure and peripheral sympathetic vascular responsiveness. Specifically, these studies test the hypothesis that androgen supplementation with HT is associated with 1) lower baroreflex gain during a lower body negative pressure (LBNP) challenge, and 2) a narrowed response frequency range that precedes impaired sympathetic vascular response dynamics in trans men compared to control cisgender women.
Study procedures include an oral glucose tolerance test (OGTT), microneurography of the median nerve in the forearm to assess SNSA, and 2 LBNP challenges designed to examine baroreflex gain during static LBNP and then the frequency of SNSA during oscillating LBNP (OLBNP). Participants complete 3 visits for this study. Visit 1 is for informed consent procedures; Visit 2 is a pre-screening visit to complete the OGTT; Visit 3 is for experimental testing to assess gain and the frequency range. Blood pressure, heart rate and muscle SNSA (MSNA) are measured during LBNP and OLBNP. MSNA is recorded using 2 microelectrodes inserted through the skin of the forearm to record activity (firing) of the median nerve. Blood samples are taken via IV placement to measure insulin and glucose during the OGTT for Visit 2, and then sex hormones and catecholamines during Visit 3. Results from the group of young trans men will be compared to a control group of cisgender women matched for age and body mass index.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- There is 1 group of trans men (n=20) and 1 group of cisgender women (n=20). Study procedures, protocols, and measurements will be the same for both groups and performed and/or taken in a similar time period.
| Arm | Type | Receives |
|---|---|---|
| Trans men | Active comparator | Other: Trans mentransgender men taking physiologic doses of testosterone for gender affirming hormone therapy |
| control | No intervention | –cisgender women not receiving testosterone and with normal sex hormone levels |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (1 listed)
- Both groups (trans men and cisgender women) must be healthy and non-smoking. Control participants must be cisgender women with regular menses every 26-34 days. Trans men participants must be currently receiving testosterone for gender affirming hormone therapy where physiologic doses of exogenous Dihydrotestosterone have been administered (via injection or transdermal application) for at least 3 months as prescribed by their local endocrine provider as part of their clinically indicated hormone therapy. Doses can vary depending on the size and goals of each patient, but blood testosterone will be between 400-1000 ng/dl.
Key exclusion criteria (3 listed)
- Subjects who smoke, have diabetes, or BP>140/90 will be excluded.
- Subjects will not be taking medications during the study, including any insulin-sensitizing or cardiovascular medications.
- Subjects are excluded if they have lost > 5 kg of weight within the past 6 months or perform high-intensity exercise > 3 times/week.
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 |
|---|---|---|
| Trans menWe are studying the effects of testosterone taken by trans men on mechanisms of blood pressure control and comparing those results to cisgender women that have normal (ie lower) testosterone levels. | Other | Trans men |
Primary outcome
Muscle Sympathetic Nerve Activity (MSNA)
Time frame: 3 hours
MSNA is recorded continuously at rest and during O/LBNP protocols with a tungsten microelectrode (0.2 diameters insulated shaft tapered to an uninsulated tip of ~1-5 μm) inserted percutaneously into the median nerve. Multiunit, postganglionic MSNA is distinguished from other sources of nerve activity by the presence of spontaneous pulse synchronous bursts, increased activity when the subject holds their breath or clenches their first (stretches forearm muscles around median nerve), or if activity does not change when the skin is stimulated by light brushing or stroking (indicates lack of skin nerve activity). Bursts of MSNA at rest and during LBNP are quantified as total activity (AU/min), burst frequency (bursts/min) and burst incidence (bursts/100 heartbeats). The MSNA burst incidence is expressed in bursts/100 heartbeats to normalize for differences in heart rate among subjects.
Systolic Blood Pressure (SBP)
Time frame: 3 hours
SBP is measured continuously with a Finometer beat-to-beat blood pressure measurement system at rest and during O/LBNP protocols. Units are mm Hg.
Diastolic Blood Pressure (DBP)
Time frame: 3 hours
DBP is measured continuously with a Finometer beat-to-beat blood pressure measurement system at rest and during O/LBNP protocols. Units are mm Hg.
Mean Arterial Pressure (MAP)
Time frame: 3 hours
MAP at rest and during O/LBNP protocols is calculated as 1/3(SBP-DBP)+DBP using the beat-to-beat SBP and DBP measurements taken with the Finometer system. Units are mm Hg.
Sympathetic Baroreflex (BR) Gain
Time frame: 3 hours
Sympathetic BR gain is used as an index of sympathetic (neural) control of blood pressure, where gain is determined by the slope of the linear relationship between MSNA (burst/100 heartbeats) and DBP (mm Hg) at rest and during LBNP. The relationship produces a negative slope in that for a given subject, when DBP falls below the normal level sustained at rest, sympathetic activity increases to restore DBP back to that normal level. Thus, more MSNA bursts are observed at lower levels of DBP and vice versa. A steeper (more negative) slope suggests greater sensitivity of the baroreceptors to changes in blood pressure, and thereby more effective sympathetic control of blood pressure. A flatter slope suggests impaired BR sensitivity and blood pressure dysfunction, which is expected for the trans men group compared to cisgender women controls.
Frequency in the Neural Cardiovascular Control
Time frame: 0.5 hours
The frequency of SBP, DBP and heart rate during OLBNP is analyzed in Matlab in a linear time-invariant system (LTI) framework. Heart rate and BP measures taken during OLBNP are low-pass filtered (0.05 Hz estimated example) and corrected for end-effects using a Hamming window. The derived impulse responses (IRs) are 1/3rd octave smoothed before calculating the frequency power spectra (0.001-0.05 Hz estimated example). The power of DBP and SBP at the OLBNP frequency are anticipated to be independently inversely related to the efficiency of BP control. Further, the difference in heart rate and SBP, and in heart rate and DBP, power at those frequencies reflects the degree of autonomic function, analogous to baroreflex gain.
Electrocardiogram (ECG)
Time frame: 3 hours
A 3-lead ECG is continuously recorded at rest and during the O/LBNP protocols. The R-wave of the QRS complex of the ECG recording will be used for measures of pulse interval by determining the amount of time in seconds between the R-waves of 2 consecutive QRS complexes.
2 secondary outcomes
Brachial Artery Mean Blood Flow Velocity
Time frame: 3 hours
Cardiovagal Baroreflex (BR) Gain
Time frame: 3 hours
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Nov 2022.
- Individual participant dataSharing planned: Undecided
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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.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
A study testing Trans men in people with Transgender Men and Blood Pressure, run by Yale University.
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 1 inclusion and 3 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: withdrawn, as of the sponsor's last update on 3 Nov 2022. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. 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 was withdrawn before enrolling participants, so there are no results.
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?
Muscle Sympathetic Nerve Activity (MSNA) (time frame: 3 hours). The study lists 7 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 3 Nov 2022.