NCT03513770

Autonomic Control of the Circulation and VDR

Autonomic Control of the Circulation and the Venous Distension Reflex

• Status: Recruiting
• Phase: EARLY_Phase 1
• Study type: Interventional
• Enrollment: 18 (estimated)
• Sponsor: Milton S. Hershey Medical Center · Academic / Other
• Sex: All
• Age: 21 Years – 35 Years
• Healthy volunteers: Accepted

Summary

The study objective of this project is to examine the mechanisms of the venous distension reflex (VDR) in humans. We hypothesize that COX blockade with ketorolac tromethamine, an intravenous NSAID, will attenuate the muscle sympathetic nerve activity (MSNA) response to limb venous distension. To gain further insight into whether the COX byproducts directly stimulate chemically-sensitive afferents, or enable venodilation and indirectly evoke afferent stimulation, we will measure vein size using 3T MRI during venous distention with and without ketorolac infusions.

Detailed description

We will use a prospective observational design to examine if a COX blockade will inhibit the MSNA response to venous distension (Aim1), and if a COX blockade will alter vein sizes during venous distension (Aim2). Each subject will serve as their own control. Aim 1: An IV will be inserted in the antecubital fossa of one arm, and the wrist-to-elbow occlusion will be performed. To block the COX system, 6 mg ketorolac tromethamine in 10 ml saline will be infused into the forearm over 1 minute (Infusion 1). After 10 minutes, a second infusion of ketorolac tromethamine (up to 3 mg) in 5% of the forearm volume of saline,( \~40-60 ml) will be infused into the occluded forearm at a rate of \~ 30 ml/min (Infusion 2). Five minutes of data will then be collected before releasing the upper arm cuff. Infusion 1 is to block the COX pathway, while infusion 2 is to induce venous distension. In the saline control trial, saline (without ketorolac) in identical volumes as those in the COX blockade trial will be performed on a separate day. Aim 2: The subject will lie supine inside the MRI scanner. The subject will be instrumented with cuffs for the wrist-to-elbow occlusion procedure on one arm, and cuffs for automated BP and HR measurements from the other arm, The images will be obtained before and during the wrist-to-elbow occlusion procedure. The sizes of veins (i.e. cross sectional area) will be measured offline.

Conditions

• Venous Distension Reflex
• Blood Pressure

Interventions

Type	Name	Description
OTHER	Wrist-to-elbow (W-E) occlusion	An IV will be inserted in the antecubital fossa of one arm. The arm will be fitted with occlusion cuffs arranged in a continuous fashion from the wrist to the elbow. A final cuff will be placed on the upper arm. The cuffs from the wrist to the elbow will be inflated to the same pressure of up to 300 mmHg using a pressurized air tank. First, the subject?s arm will be elevated and the subject will make a fist to squeeze blood from the hand. Then the wrist cuff will be inflated. Once that cuff is fully inflated, the next cuff in the sequence will be inflated. Cuffs are inflated in sequence until the elbow cuff is inflated. After a 10-15 second period to allow blood to drain, the upper arm cuff will inflate (up to 250 mmHg) to keep any additional blood from entering the forearm. Next, the cuffs on the forearm will be removed but the upper arm cuff will remain inflated.
DRUG	ketorolac tromethamine	In the COX blockade trial, just after the Wrist-to-elbow occlusion, 6 mg ketorolac tromethamine in 10 ml saline will be infused into the forearm over 1 minute. After 10 minutes, a second infusion of ketorolac tromethamine (up to 3 mg) in 5% of the forearm volume of saline,( \~40-60 ml) will be infused into the occluded forearm at a rate of \~ 30 ml/min. Five minutes of data will then be collected before releasing the upper arm cuff. Infusion 1 is to block the COX pathway, while infusion 2 is to induce venous distension.
DRUG	saline control	In the saline control trial performed on a separate day, saline (without ketorolac) in identical volumes as those in the COX blockade trial, will be infused.

Timeline

• Start date: 2019-08-14
• Primary completion: 2026-05-01
• Completion: 2026-05-30
• First posted: 2018-05-02
• Last updated: 2025-09-16

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study