HypertensionPhase 1NCT02425566
Role of Sympathetic Activity and Splanchnic Capacitance in Hypertension
A Phase 1 study testing Trimethaphan and Nitroglycerin in people with Hypertension, run by Vanderbilt University at 1 site in United States.
Trial summary
The purpose of this study is to better understand the role of the abdominal veins (splanchnic capacitance) and the sympathetic nervous system in human hypertension. The investigators will test the hypothesis that constriction of abdominal veins due to sympathetic activation contributes to human hypertension. Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Hypertension
- What is being tested?
- Trimethaphan and Nitroglycerin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 2015to Aug 2028
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
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 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Lean and obese, male and female subjects of all races between 18 and 65 years of age.
- Normotensive and hypertensive subjects will be enrolled. Hypertension will be defined as a systolic BP ≥140 mm Hg and/or a diastolic BP ≥ 90 mm Hg, taken in the seated position in at least 2 separate occasions. All subjects will be otherwise normal volunteers.
- Subjects able and willing to provide informed consent.
Who cannot join
- Pregnancy.
- Subjects with morbid obesity (BMI > 40 kg/m2).
- Subjects with any chronic disease (other than hypertension) including diabetes, cardiovascular disease, history of smoking, or if they take any medication that have known effects autonomic functions, or other factors which in the investigator's opinion would prevent the subject from completing the protocol including clinically significant abnormalities in clinical, mental or laboratory testing.
- Current smokers or history of heavy smoking (>2 packs/day)
- Lean normotensive subjects will be excluded if they have a strong family history of hypertension (both parents treated or diagnosed), diagnosis of sleep apnea or a high score in the Berlin questionnaire for sleep apnea, or if they are highly trained athletes.
Trial locations and contacts
1 site in 1 country.
United States1 site
Autonomic Dysfunction Center
Nashville, Tennessee, 37232
About this study
The purpose of this study is to better understand the role of the abdominal veins (splanchnic capacitance) and the sympathetic nervous system in human hypertension. The investigators will test the hypothesis that constriction of abdominal veins due to sympathetic activation contributes to human hypertension. Splanchnic capacitance will be assessed in normotensive and hypertensive subjects at baseline and during acute blockade of the autonomic nervous system.
Read the detailed description
The splanchnic circulation contains a highly compliant venous bed which normally stores ~25% of the blood volume, and receives up to 25% of the resting cardiac output. It is highly innervated by the sympathetic nervous system, and this neural regulation results in large volume shifts that modulate blood pressure (BP). The splanchnic circulation may play a role in hypertension as suggested by studies showing that surgical splanchnic denervation effectively lowered BP in hypertensive subjects without affecting renal function. Recently, studies in animal models have shown that splanchnic sympathetic activation, particularly to capacitance vessels, was critical to the development of hypertension. The clinical translation of these findings to human hypertension has lagged behind because of limitations in previously available experimental approaches. The investigators propose to use splanchnic radionuclide plethysmography and sympathetic withdrawal with the ganglionic blocker trimethaphan to overcome these limitations.
Several studies have shown that sympathetic activity contributes to hypertension. Accordingly, our previous studies showed that sympathetic withdrawal with the ganglionic blocker trimethaphan resulted in normalization of BP in hypertensive subjects. Interestingly, this was caused mainly by a fall in stroke volume, rather than a decrease in arterial vascular resistance suggesting that decreased venous return may play a major role, and that a sympathetically mediated contraction of splanchnic capacitance contributes to the maintenance of hypertension.
The investigators hypothesize that the decrease in BP induced by autonomic blockade with trimethaphan results from an increase in splanchnic capacitance leading to a reduction in venous return. To test this hypothesis, the investigators will compare the effect of sympathetic withdrawal on splanchnic capacitance between hypertensive and normotensive subjects. Splanchnic venous capacitance will be measured by radionuclide plethysmography. Abdominal blood volumes will be measured using labeled red cells with technetium-99 while applying different levels of continuous positive airway pressure.
In addition, the investigators will assess whether changes in splanchnic capacitance measured by bioimpedance are similar to those measured by radionuclide imaging. For this purpose, the investigators will compare the effects of nitroglycerin on splanchnic capacitance measured by the two techniques.
- Conditions
- Hypertension
- Being tested
- Trimethaphan, Nitroglycerin
- Keywords
- autonomic nervous system, hypertension, ganglionic blocker, trimethaphan, splanchnic circulation, capacitance
- Medical subject headings
- Hypertension
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TrimethaphanDrug
Also called Trimethaphan Camsylate
Trimethaphan is a Nn-nicotinic receptor antagonist that blocks sympathetic and parasympathetic transmission at the level of the autonomic ganglia. It will be administered as an acute intravenous infusion with doses ranging from 0.5 to 5.0 mg/min.
NitroglycerinDrug
Also called Nitroglycerin sublingual, nitrostat
Sublingual nitroglycerin (0.3-0.6 mg) will be given after baseline measurements.
| Study group | Role | What they receive |
|---|---|---|
| Study day with trimethaphan | Experimental | After baseline measurements, autonomic blockade will be induced by continuous intravenous infusion of trimethaphan starting at 0.5-1.0 mg/min and increasing by 1.0 mg/min every 2 to 6 minutes up to an infusion rate of 5 mg/min. Receives: Drug: Trimethaphan |
| Radionuclide Study day with nitroglycerin | Experimental | Sublingual nitroglycerin (0.3-0.6 mg) will be given after baseline measurements. Outcome measurements will be repeated within 10 min after the nitroglycerin has dissolved Receives: Drug: Nitroglycerin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Splanchnic venous capacitance
The primary outcome will be the splanchnic capacitance, defined as the pressure-venous curve (P-V curve), during trimethaphan infusion adjusted for its baseline values. For analysis, the Y-intercept (volume) and the slope of the P-V relationship during autonomic blockade adjusted by their corresponding baseline values will be compared between groups.
Measured: after 10 minutes of autonomic blockade
Secondary outcomes (2)
Systolic Blood Pressure
Changes from baseline in blood pressure.
Measured: after 10 minutes of autonomic blockade
Stroke volume
Changes from baseline in stroke volume.
Measured: after 10 minutes of autonomic blockade
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Apr 2015 (estimated)
- Study startApr 2015
- Primary completionJul 2028 (estimated)
- Study completionAug 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HypertensionStudies of the same condition, open and under way.
- 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 1
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 12 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Vanderbilt University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Italo Biaggioni, Vanderbilt University
- Investigators
- Italo Biaggioni, MD, Principal investigator, Vanderbilt University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02425566
- Sponsor's protocol ID
- 141218
- Status last verified
- Aug 2026
- First submitted
- 10 Apr 2015
- Last updated
- 27 Aug 2026
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
Okamoto LE, Dupont WD, Biaggioni I, Kronenberg MW. Effect of nitroglycerin on splanchnic and pulmonary blood volume. J Nucl Cardiol. 2022 Dec;29(6):2952-2963. doi: 10.1007/s12350-021-02811-7. Epub 2021 Nov 2.
PubMed 34729682
Study at a glance
From the registry record, last updated by the sponsor on 27 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Role of Sympathetic Activity and Splanchnic Capacitance in Hypertension
- ClinicalTrials.gov ID
- NCT02425566
- Acronym / sponsor ID
- 141218
- Conditions
- Hypertension
- Keywords
- autonomic nervous system, hypertension, ganglionic blocker, trimethaphan, splanchnic circulation, capacitance
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 12 participants (estimated)
- Lead sponsor
- Vanderbilt UniversityUniversity, hospital or other
- Study start
- Apr 2015 (actual)
- Primary completion
- Jul 2028 (estimated)
- Study completion
- Aug 2028 (estimated)
- First posted
- 24 Apr 2015 (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.
The purpose of this study is to better understand the role of the abdominal veins (splanchnic capacitance) and the sympathetic nervous system in human hypertension. The investigators will test the hypothesis that constriction of abdominal veins due to sympathetic activation contributes to human hypertension. Splanchnic capacitance will be assessed in normotensive and hypertensive subjects at baseline and during acute blockade of the autonomic nervous system.
Detailed description
The splanchnic circulation contains a highly compliant venous bed which normally stores ~25% of the blood volume, and receives up to 25% of the resting cardiac output. It is highly innervated by the sympathetic nervous system, and this neural regulation results in large volume shifts that modulate blood pressure (BP). The splanchnic circulation may play a role in hypertension as suggested by studies showing that surgical splanchnic denervation effectively lowered BP in hypertensive subjects without affecting renal function. Recently, studies in animal models have shown that splanchnic sympathetic activation, particularly to capacitance vessels, was critical to the development of hypertension. The clinical translation of these findings to human hypertension has lagged behind because of limitations in previously available experimental approaches. The investigators propose to use splanchnic radionuclide plethysmography and sympathetic withdrawal with the ganglionic blocker trimethaphan to overcome these limitations.
Several studies have shown that sympathetic activity contributes to hypertension. Accordingly, our previous studies showed that sympathetic withdrawal with the ganglionic blocker trimethaphan resulted in normalization of BP in hypertensive subjects. Interestingly, this was caused mainly by a fall in stroke volume, rather than a decrease in arterial vascular resistance suggesting that decreased venous return may play a major role, and that a sympathetically mediated contraction of splanchnic capacitance contributes to the maintenance of hypertension.
The investigators hypothesize that the decrease in BP induced by autonomic blockade with trimethaphan results from an increase in splanchnic capacitance leading to a reduction in venous return. To test this hypothesis, the investigators will compare the effect of sympathetic withdrawal on splanchnic capacitance between hypertensive and normotensive subjects. Splanchnic venous capacitance will be measured by radionuclide plethysmography. Abdominal blood volumes will be measured using labeled red cells with technetium-99 while applying different levels of continuous positive airway pressure.
In addition, the investigators will assess whether changes in splanchnic capacitance measured by bioimpedance are similar to those measured by radionuclide imaging. For this purpose, the investigators will compare the effects of nitroglycerin on splanchnic capacitance measured by the two techniques.
Study design
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Study day with trimethaphan | Experimental | Drug: TrimethaphanAfter baseline measurements, autonomic blockade will be induced by continuous intravenous infusion of trimethaphan starting at 0.5-1.0 mg/min and increasing by 1.0 mg/min every 2 to 6 minutes up to an infusion rate of 5 mg/min. |
| Radionuclide Study day with nitroglycerin | Experimental | Drug: NitroglycerinSublingual nitroglycerin (0.3-0.6 mg) will be given after baseline measurements. Outcome measurements will be repeated within 10 min after the nitroglycerin has dissolved |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Lean and obese, male and female subjects of all races between 18 and 65 years of age.
- Normotensive and hypertensive subjects will be enrolled. Hypertension will be defined as a systolic BP ≥140 mm Hg and/or a diastolic BP ≥ 90 mm Hg, taken in the seated position in at least 2 separate occasions. All subjects will be otherwise normal volunteers.
- Subjects able and willing to provide informed consent.
Key exclusion criteria (5 listed)
- Pregnancy.
- Subjects with morbid obesity (BMI > 40 kg/m2).
- Subjects with any chronic disease (other than hypertension) including diabetes, cardiovascular disease, history of smoking, or if they take any medication that have known effects autonomic functions, or other factors which in the investigator's opinion would prevent the subject from completing the protocol including clinically significant abnormalities in clinical, mental or laboratory testing.
- Current smokers or history of heavy smoking (>2 packs/day)
- Lean normotensive subjects will be excluded if they have a strong family history of hypertension (both parents treated or diagnosed), diagnosis of sleep apnea or a high score in the Berlin questionnaire for sleep apnea, or if they are highly trained athletes.
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 |
|---|---|---|
| TrimethaphanAlso: Trimethaphan CamsylateTrimethaphan is a Nn-nicotinic receptor antagonist that blocks sympathetic and parasympathetic transmission at the level of the autonomic ganglia. It will be administered as an acute intravenous infusion with doses ranging from 0.5 to 5.0 mg/min. | Drug | Study day with trimethaphan |
| NitroglycerinAlso: Nitroglycerin sublingual, nitrostatSublingual nitroglycerin (0.3-0.6 mg) will be given after baseline measurements. | Drug | Radionuclide Study day with nitroglycerin |
Primary outcome
Splanchnic venous capacitance
Time frame: after 10 minutes of autonomic blockade
The primary outcome will be the splanchnic capacitance, defined as the pressure-venous curve (P-V curve), during trimethaphan infusion adjusted for its baseline values. For analysis, the Y-intercept (volume) and the slope of the P-V relationship during autonomic blockade adjusted by their corresponding baseline values will be compared between groups.
2 secondary outcomes
Systolic Blood Pressure
Time frame: after 10 minutes of autonomic blockade
Stroke volume
Time frame: after 10 minutes of autonomic blockade
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Aug 2026.
- Derived from this study: PubMed 34729682Okamoto LE, Dupont WD, Biaggioni I, Kronenberg MW. Effect of nitroglycerin on splanchnic and pulmonary blood volume. J Nucl Cardiol. 2022 Dec;29(6):2952-2963. doi: 10.1007/s12350-021-02811-7. Epub 2021 Nov 2.
- 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.
Italo Biaggioni, MD principal investigator
Vanderbilt University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Trimethaphan and Nitroglycerin in people with Hypertension, run by Vanderbilt University 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 3 inclusion and 5 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: under way, not looking for participants, as of the sponsor's last update on 27 Aug 2026. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
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?
Splanchnic venous capacitance (time frame: after 10 minutes of autonomic blockade). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02425566, which also lists 1 linked publication.
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 27 Aug 2026.