The Venous Distension Reflex and Orthostatic Hypertension

NCT03496792 | Recruiting

• 1 other identifier: STUDY00007397
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

This research is being done to find out whether distension of veins in legs will cause a rise in blood pressure (orthostatic hypertension).

Conditions

Blood Pressure

Keywords

venous distension reflex

Outcome Measures

Primary Outcomes (1)

• Muscle Sympathetic Nerve Activity (MSNA) in bursts/min or arbitrary units/min

  MSNA provides direct recordings of sympathetic nerve activity directed to blood vessels in skeletal muscle.

  Recorded continuously during Visit 2, the 4-5 hr Negative Pressure study visit.

Secondary Outcomes (2)

• Blood pressure in mmHg

  Recorded continuously during the 4-5 hr visit.

• Heart rate in beats per minute

  Recorded continuously during the 4-5 hr visit.

Study Arms (4)

Tilt + external pressure

EXPERIMENTAL

Tilt + external pressure on legs performed in both "BP elevated with standing" and "BP maintained with standing" groups.

Other: Tilt + external pressure

Tilt + no external pressure

PLACEBO COMPARATOR

Tilt + no external pressure performed in both "BP elevated with standing" and "BP maintained with standing" groups.

Other: Tilt + no external pressure.

Limb occlusion + negative pressure

EXPERIMENTAL

Limb occlusion + negative pressure performed in both "BP elevated with standing" and "BP maintained with standing" groups.

Other: Limb occlusion + negative pressure

Limb occlusion + no negative pressure

PLACEBO COMPARATOR

Limb occlusion + no negative pressure performed in both "BP elevated with standing" and "BP maintained with standing" groups.

Other: Limb occlusion + no negative pressure

Interventions

Tilt + external pressure OTHER

In Visit 1, the anti-shock trousers will be inflated to 20, 40, or 60 mmHg. BP will be measured 3 times from the brachial artery. Then the table will be tilted head up to a maximum of 70o for up to 10 min, while BP will be measured from the brachial artery at 1 min intervals. The tilt table is returned to 0o and the resting supine baseline BP will be collected. Then, the anti-shock trousers will be inflated to a different pressure (20, 40, or 60 mmHg) and the head up tilt will be repeated. Repetitions at the various pressures will be performed in a random order with suitable resting intervals in between the tilting bouts.

Tilt + external pressure

Tilt + no external pressure. OTHER

In Visit 1, the anti-shock trousers will NOT be inflated. Auscultatory BP will be measured 3 times from the brachial artery. Thereafter, the table will be tilted head up to a maximum of 70o for up to 10 min, while BP will be measured from the brachial artery at 1 min intervals.

Tilt + no external pressure

Limb occlusion + negative pressure OTHER

In Visit 2, a cuff will be placed on the thigh of a leg that is sealed in an airtight pressure tank. After the cuff is inflated to 250 mmHg, the pressure in the tank will be reduced to -100mmHg for 2 minutes. The application of negative pressure creates a suction effect on the leg, and leads to an overall increase in pressure gradient across the blood vessel wall and induces vascular distension.

Limb occlusion + negative pressure

Limb occlusion + no negative pressure OTHER

In Visit 2, a cuff will be placed on the thigh of a leg that is sealed in an airtight pressure tank. The cuff is inflated to 250 mmHg for 2 minutes, but the pressure in the tank is not changed.

Limb occlusion + no negative pressure

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Are capable of giving informed consent
• Are of any race or ethnicity
• Are fluent in written and spoken English

You may not qualify if:

• Are 18 years of age
• For subjects with elevated standing BP
• Systolic BP (SBP) during standing is at least 10 mmHg \> the supine SBP
• Patients with a diagnosis of stage I hypertension without other chronic diseases may be INCLUDED
• For normal subjects without elevated standing BP
• The change in SBP by standing is within ± 5 mmHg from the supine SBP
• Matched gender, similar age and BMI (within 10%) to participants with elevated standing BP
• Free of acute or chronic medical conditions
• Age \< 18 years of age
• Are a pregnant or nursing woman
• Are a prisoner or institutionalized individual or unable to consent
• Have chronic diseases (e.g. heart, lung, neuromuscular disease, or cancer) other than stage I hypertension
• Have orthostatic hypotension or a history of syncope
• Current smoker
• History of blood clots

Sponsors & Collaborators

• Milton S. Hershey Medical Center: lead

Study Sites (1)

Penn State Milton S. Hershey Medical Center

Hershey, Pennsylvania, 17033, United States

RECRUITING

Related Publications (6)

• Cui J, Blaha C, Herr MD, Drew RC, Muller MD, Sinoway LI. Limb suction evoked during arterial occlusion causes systemic sympathetic activity in humans. Am J Physiol Regul Integr Comp Physiol. 2015 Sep;309(5):R482-8. doi: 10.1152/ajpregu.00117.2015. Epub 2015 Jul 1.

  PMID: 26136530 BACKGROUND

• Cui J, Gao Z, Blaha C, Herr MD, Mast J, Sinoway LI. Distension of central great vein decreases sympathetic outflow in humans. Am J Physiol Heart Circ Physiol. 2013 Aug 1;305(3):H378-85. doi: 10.1152/ajpheart.00019.2013. Epub 2013 May 31.

  PMID: 23729210 BACKGROUND

• Cui J, Leuenberger UA, Gao Z, Sinoway LI. Sympathetic and cardiovascular responses to venous distension in an occluded limb. Am J Physiol Regul Integr Comp Physiol. 2011 Dec;301(6):R1831-7. doi: 10.1152/ajpregu.00170.2011. Epub 2011 Sep 21.

  PMID: 21940404 BACKGROUND

• Cui J, McQuillan PM, Blaha C, Kunselman AR, Sinoway LI. Limb venous distension evokes sympathetic activation via stimulation of the limb afferents in humans. Am J Physiol Heart Circ Physiol. 2012 Aug 15;303(4):H457-63. doi: 10.1152/ajpheart.00236.2012. Epub 2012 Jun 15.

  PMID: 22707559 BACKGROUND

• Cui J, McQuillan P, Moradkhan R, Pagana C, Sinoway LI. Sympathetic responses during saline infusion into the veins of an occluded limb. J Physiol. 2009 Jul 15;587(Pt 14):3619-28. doi: 10.1113/jphysiol.2009.173237. Epub 2009 May 26.

  PMID: 19470776 BACKGROUND

• Kario K. Orthostatic hypertension-a new haemodynamic cardiovascular risk factor. Nat Rev Nephrol. 2013 Dec;9(12):726-38. doi: 10.1038/nrneph.2013.224. Epub 2013 Nov 5.

  PMID: 24189649 BACKGROUND

Study Officials

• Jian Cui

  Penn State College of Medicine

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jian Cui, PhD

CONTACT

717-531-1799; jcui@pennstatehealth.psu.edu

Kris Gray

CONTACT

717-531-4589; kgray1@pennstatehealth.psu.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Outcomes assessor will not know trial intervention prior to data analysis.
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Medicine

Model Details: The investigators will examine if individuals with elevated standing blood pressure have a heightened VDR. Two groups of subjects, "BP elevated with standing" group and "BP maintained with standing" group will be examined for this experiment. The tilt + external pressure and tilt + no external pressure, or the limb occlusion + negative pressure and limb occlusion + no negative pressure trials will be performed in random order using a Latin Square design. Because the nature of the interventions, neither the subjects nor the investigators can be blinded to the interventions

Study Record Dates

• First Submitted: February 15, 2018
• First Posted: April 12, 2018
• Study Start: March 10, 2020
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): August 30, 2026
• Last Updated: March 30, 2026

Record last verified: 2026-03

Locations

US (1)