Sympathetic Vasoconstriction Blockade for Obesity

Overseen By Italo Biaggioni, MD

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Vanderbilt University Medical Center

Must be taking: Metformin

Must not be taking: SNRIs, NET inhibitors, PDE5 inhibitors, anticoagulants

Disqualifiers: Pregnancy, Smoking, Cardiovascular disease, others

Compensation: Varies

Number of Visits: Unknown

Duration: 2 sessions, at least 4 weeks apart

36 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to better understand the contribution of sympathetic vasoconstriction to impaired insulin-mediated vasodilation and subsequently insulin-mediated glucose uptake. The investigators will test the hypothesis that removal of sympathetic vasoconstriction can result in improvement in insulin-mediated vasodilation and subsequently sensitivity to insulin-mediated glucose uptake.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications, such as serotonin-norepinephrine reuptake inhibitors, norepinephrine transporter inhibitors, phosphodiesterase 5 inhibitors, anticoagulants, and chronic systemic glucocorticoid therapy. If you are on these medications, you may need to stop them to participate.

What data supports the effectiveness of the drug Phentolamine for obesity?

Research shows that Phentolamine, which blocks certain nerve signals, can cause similar blood vessel widening in both obese and lean individuals, suggesting it might help manage blood flow issues related to obesity. ^{1 2 3 4 5}

How does the drug Phentolamine and Sodium Nitroprusside work for obesity?

This drug combination is unique because it targets the sympathetic nervous system, which is often overactive in obesity, by using Phentolamine to block alpha-adrenergic receptors and Sodium Nitroprusside to promote vasodilation (widening of blood vessels). This approach may help manage obesity-related issues by reducing blood vessel constriction and improving blood flow, which is different from typical weight loss treatments that focus on diet and exercise. ^{1 3 4 6 7}

Eligibility Criteria

This trial is for adults aged 18-60 with obesity (BMI between 30-40) and insulin resistance, but not severe diabetes. Participants can be well-controlled type 2 diabetics on metformin. Exclusions include those on anticoagulants, with morbid obesity or cardiovascular disease, drug abuse history, heavy smokers, or certain medication users.

Inclusion Criteria

I have insulin resistance or am a well-controlled type 2 diabetic on metformin.

Able and willing to provide informed consent

I have insulin resistance or am a well-controlled type 2 diabetic on metformin.

Exclusion Criteria

Other factors which in the investigator's opinion would prevent the subject from completing the protocol (i.e., clinically significant abnormalities on clinical, mental examination or laboratory testing or inability to comply with protocol)

Previous allergic reaction to study medications

You have a history of alcohol or drug abuse.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo two separate experimental sessions with either phentolamine or saline control to assess insulin-mediated microvascular recruitment and glucose uptake

2 sessions, at least 4 weeks apart

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Phentolamine
• Saline
• Sodium Nitroprusside

Trial Overview The study tests if blocking sympathetic vasoconstriction improves insulin-induced vasodilation and glucose uptake in obese individuals. It involves administering Phentolamine (blocks adrenaline effects), Saline (a placebo), and Sodium Nitroprusside (enhances blood flow).

Participant Groups

Group I: Blocked Day Experimental Treatment 1 Intervention

Phentolamine

Group II: Vasodilator Comparison Active Control 1 Intervention

Sodium Nitroprusside

Group III: Intact Day Placebo Group 1 Intervention

Saline

Phentolamine is already approved in United States, Canada, European Union for the following indications:

Approved in United States as Regitine for:

• Hypertension
• Pheochromocytoma

Approved in Canada as Phentolamine for:

• Hypertension
• Pheochromocytoma

Approved in European Union as Phentolamine for:

• Hypertension
• Pheochromocytoma

Who Is Running the Clinical Trial?

Vanderbilt University Medical Center

Lead Sponsor

Trials

922

Recruited

939,000+

References

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

Autonomic Blockade Reverses Endothelial Dysfunction in Obesity-Associated Hypertension. [2022]

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

Influence of sibutramine treatment on sympathetic vasomotor tone in obese subjects. [2012]

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

Impaired endothelium-dependent vasodilation in normotensive and normoglycemic obese adult humans. [2016]

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

Dissociation between sympathetic nerve traffic and sympathetically mediated vascular tone in normotensive human obesity. [2021]

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

Augmented Endothelial-Specific L-Arginine Transport Blunts the Contribution of the Sympathetic Nervous System to Obesity Induced Hypertension in Mice. [2018]

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

Baroreflex sensitivity in the canine model of obesity-induced hypertension. [2017]

7. England pubmed.ncbi.nlm.nih.gov

Control of the forearm microcirculation: interactions with measures of obesity and noradrenaline kinetics. [2020]