Trimethaphan for High Blood Pressure

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Vanderbilt University

Disqualifiers: Pregnancy, Diabetes, Aortic aneurysms, others

Compensation: Varies

Number of Visits: 3

2 Participants Needed

Trial Summary

Do I need to stop my current medications for the trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators for more details.

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

Trimethaphan is unique because it works by blocking nerve signals that cause blood vessels to tighten, which is different from many other blood pressure medications that often target hormones or fluid balance. This mechanism can lead to a rapid decrease in blood pressure, making it useful in emergency situations. ^{1 2 3 4 5}

What is the purpose of this trial?

The purpose of this study is to learn more about the regulation of the veins of the abdomen by the autonomic (involuntary) nervous system, and how this may affect high blood pressure. Normally, the autonomic nervous system controls how much blood flows in the veins. In people with high blood pressure, however, the autonomic nervous system is changed. This change may affect the way blood flows in the veins of the abdomen which may play a role in their high blood pressure. About 32 participants will be screened for the study. The investigators estimate 16 will be eligible to participate in all of the study days.

Research Team

Italo Biaggioni, MD

Principal Investigator

Vanderbilt University

Eligibility Criteria

This trial is for adults aged 40-80 with Multiple System Atrophy and specific blood pressure conditions: high blood pressure when lying down (≥150 mmHg) and a significant drop upon standing. Participants must be able to consent and have no recent major surgeries, severe reflux, implanted medical devices in the abdomen, or systemic illnesses like diabetes that affect nerves.

Inclusion Criteria

I experience a significant drop in blood pressure when standing, due to nerve issues.

Supine hypertension, defined as systolic blood pressure ≥150 mmHg measured on two separate occasions

I am between 40 and 80 years old and may have Multiple System Atrophy.

Exclusion Criteria

I have severe acid reflux.

I have had recent fractures in my ribs or spine.

I have no devices in my abdomen that would affect pressure application.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 or more visits (in-person)

Study Day 1

Participants undergo a randomized, single blind, crossover study with either trimethaphan or placebo

1 day

1 visit (in-person)

Study Day 2

Participants undergo the second part of the crossover study with the alternate treatment (trimethaphan or placebo)

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Placebo
• Trimethaphan

Trial Overview The study is testing Trimethaphan against a placebo to understand how the autonomic nervous system's control of abdominal veins affects blood pressure. It aims to involve about 16 eligible participants who will receive either the drug or placebo to see if there's an impact on their hypertension.

Participant Groups

Group I: Trimethaphan Experimental Treatment 1 Intervention

The investigator will measure cardiac output by studying the air the participant breathes in and out. The participant will also wear a facemask to apply a low air pressure to the airway. After this, the trimethaphan infusion will begin with a small dose and the investigators increase at 1-2 minute intervals for up to five doses. The measurements will be collected again. Next, a standard blood pressure cuffs will be wrapped around the participant's abdomen. the cuff will inflate to apply pressure for 5 - 15 minutes.

Group II: Placebo Placebo Group 1 Intervention

The investigator will measure cardiac output by studying the air the participant breathes in and out. The participant will also wear a facemask to apply a low air pressure to the airway. After this, the placebo (saline) infusion will begin with a small dose and the investigators increase at 1-2 minute intervals for up to five doses. The measurements will be collected again. Next, a standard blood pressure cuffs will be wrapped around the participant's abdomen. the cuff will inflate to apply pressure for 5 - 15 minutes.

Who Is Running the Clinical Trial?

Vanderbilt University

Lead Sponsor

Trials

714

Recruited

6,143,000+

References

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

Oxygen radical scavengers and renal protection by indapamide diuretic in salt-induced hypertension of Dahl strain rats. [2015]

2. Japan pubmed.ncbi.nlm.nih.gov

[Effects of chronic oral administration of ketanserin and trichlormethiazide on blood pressure in stroke-prone spontaneously hypertensive rats]. [2013]

3. China pubmed.ncbi.nlm.nih.gov

[The effect of indapamide on plasma prostaglandins in hypertensive patients]. [2013]

4. New Zealand pubmed.ncbi.nlm.nih.gov

Three in one: safety, efficacy, and patient acceptability of triple fixed-dose combination medicine in the management of hypertension. [2021]

5. New Zealand pubmed.ncbi.nlm.nih.gov

Valsartan/hydrochlorothiazide: a review of its pharmacology, therapeutic efficacy and place in the management of hypertension. [2018]