Autonomic Blockade for High Blood Pressure

Overseen By Alfredo Gamboa, M.D.

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Vanderbilt University

Must not be taking: Autonomic drugs

Disqualifiers: Pregnancy, Morbid obesity, Diabetes, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 2

Duration: 1 day

12 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial requires that participants do not take any medications that affect autonomic functions, so you may need to stop certain medications if they influence these functions.

How does the drug Trimethaphan differ from other treatments for high blood pressure?

Trimethaphan is unique because it induces a complete autonomic blockade, which means it temporarily shuts down the autonomic nervous system that controls involuntary body functions like heart rate and blood pressure. This is different from other treatments that typically target specific pathways or receptors to lower blood pressure. ^{1 2 3 4 5}

What evidence supports the effectiveness of the drug for high blood pressure?

Trimethaphan is known to lower blood pressure by reducing systemic vascular resistance, as seen in its use during surgeries and in treating severe hypertension. Additionally, trimazosin, a similar drug, has been shown to effectively reduce blood pressure in patients with mild to moderate hypertension by dilating blood vessels. ^{1 2 3 4 6}

Who Is on the Research Team?

Italo Biaggioni, MD

Principal Investigator

Vanderbilt University

Are You a Good Fit for This Trial?

This trial is for men and women aged 18-65 with high blood pressure, not on medication affecting autonomic functions, and without chronic diseases like diabetes or cardiovascular issues. Participants should be non-smokers, not pregnant, have a BMI under 40 kg/m2, and no strong family history of hypertension in lean normotensive subjects.

Inclusion Criteria

Subjects able and willing to provide informed consent

I have normal blood pressure or controlled high blood pressure.

Exclusion Criteria

My BMI is over 40.

I do not have a strong family history of high blood pressure, sleep apnea, and I am not a highly trained athlete.

I am a current smoker or have a history of heavy smoking.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Assessment

Baseline measurements of splanchnic capacitance and blood pressure are taken

1 day

1 visit (in-person)

Treatment

Participants undergo autonomic blockade with trimethaphan and receive nitroglycerin to assess changes in splanchnic capacitance

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Nitroglycerin
• Trimethaphan

Trial Overview The study aims to understand the role of abdominal veins (splanchnic capacitance) and sympathetic nervous system activity in hypertension by using Trimethaphan and Nitroglycerin to block autonomic nervous system signals temporarily.

How Is the Trial Designed?

Group I: Study day with trimethaphan Experimental Treatment 1 Intervention

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.

Group II: Radionuclide Study day with nitroglycerin Experimental Treatment 1 Intervention

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

Who Is Running the Clinical Trial?

Vanderbilt University

Lead Sponsor

Trials

714

Recruited

6,143,000+

Citations

1. United States pubmed.ncbi.nlm.nih.gov

Ultra-high dose trimethaphan in an infant with severe hypertension. [2019]

2. United States pubmed.ncbi.nlm.nih.gov

Profile of trimazosin: an effective and safe antihypertensive agent. [2019]

3. England pubmed.ncbi.nlm.nih.gov

Sustained complete autonomic blockade. [2019]

4. United States pubmed.ncbi.nlm.nih.gov

Autonomic, systemic, and renal hemodynamic actions of trimazosin in hypertensive patients. [2019]

5. United States pubmed.ncbi.nlm.nih.gov

Autonomic cardiovascular control during a novel pharmacologic alternative to ganglionic blockade. [2016]

6. United States pubmed.ncbi.nlm.nih.gov

A comparison of the cardiovascular effects of sodium nitroprusside and trimethaphan. [2019]