Recruiting
Early Phase 1

Observational Study

Sponsor:

Milton S. Hershey Medical Center

Code:

NCT03513770

Conditions

Venous Distension Reflex

Blood Pressure

Eligibility Criteria

Sex: All

Age: 21 - 35

Healthy Volunteers: Accepted

Interventions

Wrist-to-elbow (W-E) occlusion

ketorolac tromethamine

saline control

Study Details

Brief 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.

Conditions

Venous Distension Reflex

Blood Pressure

Study ID

NCT03513770

Start date

Aug 14, 2019

Status verified date

Jul, 2026

Completion date

Nov 1, 2027

Anticipated

Primary completion date

Nov 1, 2026

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 21 - 35

Healthy Volunteers: Accepted

Inclusion Criteria

  • Are capable of giving informed consent
  • Are any race or ethnicity
  • Are fluent in written and spoken English
  • Have a satisfactory history and physical exam to meet inclusion/exclusion criteria
  • Are free of acute or chronic medical conditions
  • Are 21 - 35 years of age (inclusive)
  • Weigh over 50 kg

Exclusion Criteria

  • Are less than 21 or over 35 years of age
  • Are Pregnant or nursing women
  • Are prisoners or institutionalized individuals or unable to consent
  • Any chronic diseases (hypertension, heart, lung, neuromuscular disease, kidney disease, diabetes or cancer).
  • Are taking medications that may affect their cardiovascular or nervous system
  • Has taken an NSAID within 48 hours of any visit (visit will need to be rescheduled)
  • Has never taken NSAIDs and therefore would not know if they are allergic to it
  • Have a supine BP >140/90 mmHg
  • Have known allergy to ibuprofen-like drugs (NSAIDS) or aspirin
  • Have history of asthma or nasal polyps
  • Have history of GI bleeding or ulcers
  • Subjects with ferromagnetic metal implants
  • Subjects who are claustrophobic

Study Design

Enrollment

18 participants

Anticipated

Allocation

Randomized

Intervention Model

Crossover

Primary purpose

Basic Science

Interventions and Outcome Measures

Arms

experimental: Ketorolac

The Wrist-to-Elbow occlusion procedure will be performed followed by 2 ketorolac tromethamine + saline infusions into the occluded arm.

placebo comparator: Control

The Wrist-to-Elbow occlusion procedure will be performed followed by 2 saline only infusions into the occluded arm.

Interventions

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.

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.

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.

Primary outcome measure

  • Microneurography (MSNA) [ Time Frame: Recorded continuously during the 3-4 hour study visit ]
  • Vein size with MRI [ Time Frame: Recorded continuously during the 3-4 hour study visit ]

Central Contacts and Locations

Locations

Penn State Milton S. Hershey Medical Center

Recruiting

Hershey, Pennsylvania, United States, 17033

Contacts

Jian Cui

7175311799jcui@pennstatehealth.psu.edu

Kris Gray

717-531-4589ksgray@psu.edu

More Information

Sponsor

Milton S. Hershey Medical Center

Last update posted

Jul 9, 2026

Last verified

Jul, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by Milton S. Hershey Medical Center on 2026-07-09.