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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how trimethaphan, a drug used to manage high blood pressure, might help by examining how the body's involuntary nervous system controls blood flow in the abdomen. Researchers aim to determine if changes in this system affect blood pressure in individuals with Multiple System Atrophy, a condition often causing a significant blood pressure drop when standing. Those diagnosed with Multiple System Atrophy who experience high blood pressure when lying down and a large drop when standing might be suitable candidates. Participants will receive either trimethaphan or a placebo to compare effects on blood flow and pressure. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the chance to be among the first to receive this treatment.

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.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that trimethaphan safely controls blood pressure during surgeries. It effectively lowers blood pressure when it suddenly rises. However, some side effects may occur, including trouble urinating, dizziness when standing, a fast heartbeat, and more common issues like nausea or a dry mouth.

This study is in the early stages, so researchers are primarily focused on assessing the treatment's safety. During these initial trials, doctors closely monitor participants to ensure safety and manage any side effects. If considering joining a trial, medical staff will closely monitor your health throughout the process. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for high blood pressure?

Most treatments for high blood pressure, like ACE inhibitors or beta-blockers, focus on relaxing blood vessels or slowing heart rate. However, trimethaphan works differently by blocking nerve impulses that affect blood pressure, which could offer an alternative for patients who don't respond well to existing medications. Additionally, trimethaphan is administered via infusion and can be carefully adjusted in real time, allowing for precise control of blood pressure. Researchers are excited about trimethaphan because its unique mechanism of action and delivery method may lead to faster and more flexible management of high blood pressure.

What evidence suggests that trimethaphan might be an effective treatment for high blood pressure?

Research has shown that Trimethaphan, which participants in this trial may receive, can quickly and reliably lower blood pressure. Medical professionals often use it during surgeries and emergencies when a rapid reduction of high blood pressure is necessary. Studies indicate that it works by blocking certain nerve signals, helping to control blood pressure without causing dangerous drops. Notably, it does not cause major side effects such as a sudden increase in blood pressure after discontinuation or prolonged low blood pressure. This makes Trimethaphan a promising option for managing high blood pressure. ^{1 2 3 6 7}

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 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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/8695090/

Trimethaphan (Arfonad) control of hypertension and ... No rebound hypertension, prolonged hypotension, arrhythmias, or other side effects were noted. Trimethaphan did not alter seizure duration.

2. sciencedirect.com sciencedirect.com/topics/medicine-and-dentistry/trimetaphan

Trimetaphan - an overview | ScienceDirect Topics Blood pressure is lowered rapidly and consistently but rarely below normal. The first dose is usually effective and the action persists for several hours. The ...

3. go.drugbank.com go.drugbank.com/drugs/DB01116

Trimethaphan: Uses, Interactions, Mechanism of Action For the controlled reduction of blood pressure during surgery and in the treatment of hypertensive emergencies.

4. sciencedirect.com sciencedirect.com/topics/pharmacology-toxicology-and-pharmaceutical-science/trimetaphan-camsilate

Trimetaphan Camsilate - an overview Trimethaphan is used for the controlled reduction in blood pressure during surgical interventions, for quick regulation during sharp increases in blood pressure ...

5. ahajournals.org ahajournals.org/doi/10.1161/HYPERTENSIONAHA.118.11550

Aging Alters the Relative Contributions of the Sympathetic ... These data suggest loss of parasympathetic tone and increased sympathetic tone with aging contribute to the increase in blood pressure with age in women.

6. sciencedirect.com sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/trimetaphan-camsilate

Trimetaphan Camsilate - an overview In the presence of trimethaphan, no effect of water on blood pressure was observed. Administration of a comparable volume of 5% dextrose solution intravenously ...

7. pubchem.ncbi.nlm.nih.gov pubchem.ncbi.nlm.nih.gov/compound/Trimethaphan

Trimethaphan | C22H25N2OS+ | CID 23576 - PubChem - NIH Trimethaphan may cause urinary retention, orthostatic hypotension, tachycardia, precipitation of angina, anorexia, nausea, vomiting, dry mouth, extreme weakness ...