Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

The Venous Distension Reflex and Orthostatic Hypertension (OH)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03496792
Recruitment Status : Suspended (Temporarily suspended due to Pandemic)
First Posted : April 12, 2018
Last Update Posted : April 20, 2020
Sponsor:
Information provided by (Responsible Party):
Jian Cui, Milton S. Hershey Medical Center

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).

Condition or disease Intervention/treatment Phase
Blood Pressure Other: Tilt + external pressure Other: Tilt + no external pressure. Other: Limb occlusion + negative pressure Other: Limb occlusion + no negative pressure Not Applicable

Detailed Description:

In humans, two-thirds of the blood volume is contained within the venous vasculature. Because of this, changes in peripheral blood volume and alterations in the mechanical properties of peripheral veins can greatly impact cardiac filling, cardiac output and blood pressure (BP) responses to physiologic stress. Work from our laboratory over the past seven years has shown that local upper limb venous distension via volume infusion into an occluded arm (i.e. volume infusion model) or applying negative pressure to an occluded leg (limb suction experimental model) leads to an acute and dramatic increase in Muscle Sympathetic Nerve Activity (MSNA; an index of sympathetic activity directed to skeletal muscle) and BP in humans. Since this venous distension reflex (VDR) differs physiologically from the other reflex systems, and since this system may play a critical role in orthostatic BP control, we believe that it is a significant area of study.

The investigators speculate that VDR from lower limbs contributes to the autonomic adjustment to orthostatic stress. To examine the VDR in lower limbs, an arterial occlusion cuff on the mid-thigh was inflated (250 mm mercury; Hg). Then, limb suction (-100 mmHg) was applied ~10-15 cm below the level of arterial occlusion (i.e. below the knee). MSNA was measured in the opposite control limb. When suction was applied below the level of arterial occlusion (i.e. occlusion + suction), both MSNA and mean arterial BP (MAP) increased. In control trials, arterial occlusion without limb suction (i.e. occlusion alone) did not increase MSNA. Plethysmographic data showed calf circumference increased without detectable arterial pulsations. Pilot data suggest that the fluid shifts from the occluded but non-depressurized zone of the limb (i.e. between the cuff and knee) into the occluded and depressurized region of the limb within the tank. Thus, the results suggest that the VDR was engaged with this limb suction experimental model.

These experimental models "selectively" alter peripheral venous volume as the investigators measure sympathetic reflex responses. This approach is innovative and allows examination of a previously overlooked autonomic reflex in conscious humans. If these studies confirm the hypotheses, the obtained data would challenge the present teaching regarding how the sympathetic nervous system is engaged in humans during postural stress.

In ~2.5-10% of the population, BP rises as the person stands. This has been termed orthostatic hypertension, and is different from the "normal" sustained BP response when a person stands. The incidence of orthostatic hypertension may increase with aging (~2.4% for 45-64 years old and ~8.7% for >70 years old). Orthostatic hypertension is a risk factor for the development of stroke, left ventricular hypertrophy, and chronic kidney disease. It is unclear why BP rises with standing in some individuals. Some investigators have speculated that orthostatic hypertension is due to exaggerated baroreceptor withdrawal with standing. Others have speculated that this response is due to an increase in sympathetic output. It has been noted that some patients with orthostatic hypertension have increased venous pooling in their lower legs. Based these data, the investigators postulate that heightened engagement of the VDR reflexly increases MSNA and also serves to reset the aortic baroreflex. In this protocol, the investigators will determine if the MSNA response to leg suction is heightened in the individuals with elevated standing BP, and examine if the baroreflex is altered in these individuals. The investigators will also examine if external pressure on lower limbs, which limits the venous pooling in the lower limbs, will attenuate the increase in BP during standing in those individuals.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: 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
Masking: Single (Outcomes Assessor)
Masking Description: Outcomes assessor will not know trial intervention prior to data analysis.
Primary Purpose: Basic Science
Official Title: The Venous Distension Reflex and Orthostatic Hypertension
Actual Study Start Date : December 11, 2017
Estimated Primary Completion Date : June 30, 2024
Estimated Study Completion Date : June 30, 2024

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Tilt + external pressure
Tilt + external pressure on legs performed in both "BP elevated with standing" and "BP maintained with standing" groups.
Other: Tilt + external pressure
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.

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

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

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




Primary Outcome Measures :
  1. Muscle Sympathetic Nerve Activity (MSNA) in bursts/min or arbitrary units/min [ Time Frame: Recorded continuously during Visit 2, the 4-5 hr Negative Pressure study visit. ]
    MSNA provides direct recordings of sympathetic nerve activity directed to blood vessels in skeletal muscle.


Secondary Outcome Measures :
  1. Blood pressure in mmHg [ Time Frame: Recorded continuously during the 4-5 hr visit. ]
    Cuffs placed on a finger and arm will monitor blood pressure.

  2. Heart rate in beats per minute [ Time Frame: Recorded continuously during the 4-5 hr visit. ]
    Electrocardiogram (ECG) patches attached to a Cardiocap will monitor heart rate.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Are capable of giving informed consent
  • Are of any race or ethnicity
  • Are fluent in written and spoken English
  • Whose history and physical exam did not uncover any exclusion criteria
  • 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

Exclusion Criteria:

  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03496792


Locations
Layout table for location information
United States, Pennsylvania
Penn State Milton S. Hershey Medical Center
Hershey, Pennsylvania, United States, 17033
Sponsors and Collaborators
Milton S. Hershey Medical Center
Investigators
Layout table for investigator information
Principal Investigator: Jian Cui Penn State College of Medicine
Publications:
Layout table for additonal information
Responsible Party: Jian Cui, Associate Professor of Medicine, Milton S. Hershey Medical Center
ClinicalTrials.gov Identifier: NCT03496792    
Other Study ID Numbers: STUDY00007397
First Posted: April 12, 2018    Key Record Dates
Last Update Posted: April 20, 2020
Last Verified: April 2020

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Jian Cui, Milton S. Hershey Medical Center:
venous distension reflex
Additional relevant MeSH terms:
Layout table for MeSH terms
Hypertension
Dilatation, Pathologic
Vascular Diseases
Cardiovascular Diseases
Pathological Conditions, Anatomical