Hot Flashes and Neurovascular Function in Women

Sponsor

Mayo Clinic (Other)

Overall Status

Recruiting

CT.gov ID

NCT05193968

Collaborator

National Institutes of Health (NIH) (NIH), National Heart, Lung, and Blood Institute (NHLBI) (NIH)

120

Enrollment

Location

Arm

46.2

Anticipated Duration (Months)

2.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Women who experience hot flashes are at greater risk for hypertension and other cardiovascular disease. Neurovascular control mechanisms are likely to play an important role in this relationship. As such, these studies are designed to provide a major step forward in understanding the link between hot flashes and neurovascular dysfunction and, by extension, cardiovascular disease in women.

Condition or Disease	Intervention/Treatment	Phase
Hot Flashes Menopause Vasomotor System; Labile	Other: Sympathoexcitatory stressors Drug: Sodium Nitroprusside Drug: Acetylcholine Drug: Terbutaline Drug: Norepinephrine	N/A

Study Design

Study Type:

Interventional

Anticipated Enrollment :

120 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Basic Science

Official Title:

Hot Flashes and Neurovascular Function in Women

Actual Study Start Date :

Feb 24, 2022

Anticipated Primary Completion Date :

Dec 31, 2025

Anticipated Study Completion Date :

Dec 31, 2025

Arms and Interventions

Arm	Intervention/Treatment
Other: Experimental: Healthy Women Volunteers Hot Flash frequency will be assessed in the study subjects during a screening period. Participants can then chose to participate 1 or 2 study visits- Protocol 1: Microvascular function and/or Protocol 2: Autonomic function	Other: Sympathoexcitatory stressors Muscle sympathetic nerve activity will be measured continuously at baseline and in response to sympathoexcitatory stressors, including a Valsalva maneuver, isometric handgrip exercise, a cold pressor test, and stepped hypercapnia. Other Names: Valsalva maneuver, handgrip exercise, ice water, and hypercapnia Drug: Sodium Nitroprusside Sodium nitroprusside, used to test endothelium-independent vasodilation, will be infused through a brachial artery catheter at 0.25, 0.5, 1.0 and 2.0 ug/100ml tissue/min. Other Names: Forearm vascular conductance response to sodium nitroprusside Drug: Acetylcholine Acetylcholine, used to test endothelium-dependent vasodilation, will be infused through a brachial artery catheter at 1.0, 2.0, 4.0, and 8.0 μg/100ml tissue/min Other Names: Forearm vascular conductance response to acetylcholine Drug: Terbutaline Terbutaline, a β2-Adrenergic selective agonist, will be infused through a brachial artery catheter at 0.1, 0.5, 1.0, and 2.0 μg/100ml tissue/min. Other Names: Forearm vascular conductance response to terbutaline Drug: Norepinephrine Norepinephrine, an α-adrenergic vasoconstricting agent, will be infused through a brachial artery catheter at 1.0, 2.0, 4.0, and 8.0 ng/100ml tissue/min Other Names: Forearm vascular conductance response to norepinephrine

Arm

Intervention/Treatment

Other: Experimental: Healthy Women Volunteers

Hot Flash frequency will be assessed in the study subjects during a screening period. Participants can then chose to participate 1 or 2 study visits- Protocol 1: Microvascular function and/or Protocol 2: Autonomic function

Other: Sympathoexcitatory stressors

Muscle sympathetic nerve activity will be measured continuously at baseline and in response to sympathoexcitatory stressors, including a Valsalva maneuver, isometric handgrip exercise, a cold pressor test, and stepped hypercapnia.

Other Names:

Valsalva maneuver, handgrip exercise, ice water, and hypercapnia

Drug: Sodium Nitroprusside

Sodium nitroprusside, used to test endothelium-independent vasodilation, will be infused through a brachial artery catheter at 0.25, 0.5, 1.0 and 2.0 ug/100ml tissue/min.

Other Names:

Forearm vascular conductance response to sodium nitroprusside

Drug: Acetylcholine

Acetylcholine, used to test endothelium-dependent vasodilation, will be infused through a brachial artery catheter at 1.0, 2.0, 4.0, and 8.0 μg/100ml tissue/min

Other Names:

Forearm vascular conductance response to acetylcholine

Drug: Terbutaline

Terbutaline, a β2-Adrenergic selective agonist, will be infused through a brachial artery catheter at 0.1, 0.5, 1.0, and 2.0 μg/100ml tissue/min.

Other Names:

Forearm vascular conductance response to terbutaline

Drug: Norepinephrine

Norepinephrine, an α-adrenergic vasoconstricting agent, will be infused through a brachial artery catheter at 1.0, 2.0, 4.0, and 8.0 ng/100ml tissue/min

Other Names:

Forearm vascular conductance response to norepinephrine

Outcome Measures

Primary Outcome Measures

Compare microvascular function in women with low and high frequency hot flashes [Continuous measurement of vascular conductance during infusion of each drug- 3min at baseline and at each drug dose (~60min total of continuous forearm vascular conductance measurements)]
Change in forearm vascular conductance with intra-arterial drug infusions. Vascular conductance is an index of vascular tone and is assessed using a technique called venous occlusion plethysmography
Compare sympathetic function in women with low and high frequency hot flashes [Continuous measurement of muscle sympathetic nerve activity at rest and in response to stressors (~75min of continuous data collection once a sympathetic nerve signal is found)]
Muscle Sympathetic Nerve Activity will be directly using a technique called microneurography.