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Clinical Trials/NCT03970551
NCT03970551UnknownNot Applicable

Lower Body Muscle Pre-activation in Initial Orthostatic Hypotension: Effects on Orthostatic Tolerance

University of Calgary1 site in 1 country64 target enrollmentStarted: July 1, 2019Last updated:
Conditions
Interventions

Trial Snapshot

Phase
Not Applicable
Enrollment
64
Locations
1
Primary Endpoint
Magnitude of change in SBP from sitting to stand with a physical intervention

Study Overview

Brief Summary

This study is aimed primarily at providing a simple and effective form of treatment to reduce the symptoms of Initial Orthostatic Hypotension (IOH) and prevent syncope. We will first characterize the physiology of IOH, and then we will study four sit-to-stand maneuvers, each with a different stress tests to identify the role of sympathetic activity vs. simple muscle contraction in IOH. Then we will complete an additional two sit-to-stands with interventions designed to decrease the blood pressure drop (and hopefully symptoms) with initial stand. These consist of physical counter maneuvers, which may be a possible treatment that can be used to mitigate the drop in blood pressure (BP) seen in IOH during a stand and relieve presyncope symptoms.

Detailed Description

IOH is a form of orthostatic intolerance defined by a transient decrease in systolic blood pressure (SBP) by 40mmHg or diastolic blood pressure (DBP) by 20mmHg within the first 15-30 seconds of assuming a standing position from a supine or seated position. IOH commonly occurs in teenagers and young adults and is associated with presyncope symptoms such as nausea, light-headedness, and blurred vision and may sometimes lead to full syncope. These symptoms are a consequence of cerebral hypoperfusion caused by a rapid reduction in BP and are often present only during an active stand, and not with a passive tilt-table test. This suggests that a muscle activation reflex may play an important role underlying IOH. Identifying the refractory period of leg muscle activation will allow future investigators to accurately determine a common baseline seated period to allow hemodynamic recovery in patients after a stand. This will allow investigators to observe the physiological effects of repeated stands without any interference from a prior stand.

Upon standing there is a large shift of blood (approximately 500 mL) towards the lower extremities and abdomen. With this shift there is a decrease in venous return which results in a drop in BP. Subsequently, the decrease in BP activates the baroreceptors to increase sympathetic activity and reduce parasympathetic activity, which functions to restore BP by increasing heart rate (HR) and total peripheral resistance (TPR).

The underlying physiological mechanism behind the large decrease in blood pressure upon standing in IOH patients has not yet been confirmed. The most widely accepted explanation at this time involves rapid vasodilation localized to the contracting leg muscles during a stand. Research in both human and animal models from the past couple of decades have shown that skeletal muscle resistance vessels can dilate rapidly in response to, as well as in proportion to, a singular brief muscle contraction. This effect may be exaggerated in IOH patients, which could explain the decrease in TPR in IOH patients upon a stand and thus their subsequent drop in blood pressure. Current treatments of IOH include non-pharmacological interventions and physical counter-maneuvers such as standing up slowly or sitting up first before fully standing.

Physical counter-measures function to oppose the gravitational pull experienced on systemic circulation during a stand. During a stand, a large percentage of circulating blood shifts towards the lower extremities and abdomen resulting in blood pooling. Gravitational venous pooling can be minimized and opposed by performing a physical countermeasure such as a lower-body muscle contraction to translocate blood centrally. Sustained tensing of the lower-body muscles prevents further peripheral pooling in the legs and abdomen.

The investigators hypothesize that pre-activation of lower body muscles prior to standing, will attenuate the drop in SBP seen in IOH patients upon a stand, and alleviate symptoms of IOH, compared to an active stand without muscle pre-activation. The study participant will complete 14 active stands in total within a single day. The first 8 stands will be in an attempt to define the refractoriness of leg muscle activation. The next 4 stands will involve stress tests prior to standing to isolate the roles of sympathetic activity vs. simple muscle contraction. The final 2 stands will involve physical counter-maneuvers intended to mitigate the large drop in BP seen in IOH patients upon a stand.

Study Design

Study Type
Interventional
Allocation
Randomized
Intervention Model
Crossover
Primary Purpose
Treatment
Masking
None

Eligibility Criteria

Ages
18 Years to 50 Years (Adult)
Sex
All
Accepts Healthy Volunteers
Yes

Inclusion Criteria

  • •Either have initial orthostatic hypotension or are a healthy volunteer
  • •18-50 years old
  • •Male or Female
  • •Ability to travel to Libin Cardiovascular Institute of Alberta Autonomic Research Testing Lab in the Teaching, Research & Wellness Building at the University of Calgary, Calgary, AB
  • •Able and willing to provide informed consent

Exclusion Criteria

  • •Inability to stand up or perform leg exercises without assistance
  • •Sustained orthostatic hypotension past 3 minutes of standing

Arms & Interventions

No Physical Intervention

No Intervention

The participant will actively stand up from a seated position without performing any physical counter-maneuvers either prior to or following the stand.

Cold Pressor Test

Experimental

The participant will submerge their hands in ice water for approximately 45 seconds.

Intervention: Stress Test (Other)

Supine Knee Raises

Experimental

The participant will perform 30 seconds of raising their knees to their chest while sitting down before actively standing.

Intervention: Physical Counter-maneuver (Other)

Leg Crossing

Experimental

The participant will actively stand and then immediately cross their legs and tense their leg muscles for 60 seconds.

Intervention: Physical Counter-maneuver (Other)

Serial 7's Stress Test

Experimental

The participant will perform a mental arithmetic stress test for 30 seconds prior to standing.

Intervention: Stress Test (Other)

Functional Electrical Stimulation

Experimental

The participant will have their quadriceps passively contracted using mild electrical stimulation for approximately 30 seconds prior to standing.

Intervention: Functional Electrical Stimulation (Other)

Outcomes

Primary Outcomes

Magnitude of change in SBP from sitting to stand with a physical intervention

Time Frame: < 5 minutes

The magnitude of change in SBP from sitting to stand when the participant performs muscle pre-activation before a stand compared to no intervention at all.

Secondary Outcomes

  • Differences in Vanderbilt Orthostatic Symptoms Score (VOSS) Symptom Rating(< 5 minutes)
  • Nadir SBP(< 5 minutes)
  • Peak HR(< 5 minutes)
  • Cerebral Blood Flow Velocity (CBFV)(< 5 minutes)

Investigators

Sponsor Class
Other
Responsible Party
Sponsor

Study Sites (1)

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