Lower Body Muscle Pre-activation in Initial Orthostatic Hypotension
NCT ID: NCT03970551
Last Updated: 2021-04-29
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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UNKNOWN
NA
64 participants
INTERVENTIONAL
2019-07-01
2023-12-31
Brief Summary
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Detailed Description
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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.
The first 8 stands will be performed from a seated position. They will begin at a 20 minute seated baseline before the first stand, then in a random order perform stands after baseline durations of 30 sec, 2 min, 3 min, 4 min, 5 min, 7 min, and 10 min.
The next 4 stands will also be performed from a seated position. The interventions that will be performed in a random order are: (1) free stand with no intervention, (2) Serial 7's mental arithmetic stress test, (3) Cold Pressor stress test, (4) functional electrical stimulation.
The final 2 stands will be performed from a seated position as well. The interventions that will be performed in a random order are: (1) supine knee raises and tensing prior to standing and (2) leg crossing and tensing after standing. The entire study will take approximately 3-4 hours.
The study participant will be instrumented in a fasting state and on an empty bladder. The investigators will apply skin electrodes to continuously monitor heart rate and record an ECG. BP will be monitored continuously using finger volume clamp photoplethysmography and calibrated with intermittent brachial cuff measurements. From the continuous BP waveform, the investigators can obtain an estimate of stroke volume, cardiac output, and systemic vascular resistance (Modelflow). Oxygen saturation will be assessed from a finger probe. Middle cerebral blood flow velocity will be assessed using transcranial doppler (TCD).
Conditions
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Study Design
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RANDOMIZED
CROSSOVER
TREATMENT
NONE
Study Groups
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No Physical Intervention
The participant will actively stand up from a seated position without performing any physical counter-maneuvers either prior to or following the stand.
No interventions assigned to this group
Supine Knee Raises
The participant will perform 30 seconds of raising their knees to their chest while sitting down before actively standing.
Physical Counter-maneuver
Physical counter-maneuver targeted at minimizing the large drop in BP seen in IOH patients.
Leg Crossing
The participant will actively stand and then immediately cross their legs and tense their leg muscles for 60 seconds.
Physical Counter-maneuver
Physical counter-maneuver targeted at minimizing the large drop in BP seen in IOH patients.
Cold Pressor Test
The participant will submerge their hands in ice water for approximately 45 seconds.
Stress Test
Stress test involving submerging your hand in ice water or performing mental arithmetic to increase sympathetic activity.
Serial 7's Stress Test
The participant will perform a mental arithmetic stress test for 30 seconds prior to standing.
Stress Test
Stress test involving submerging your hand in ice water or performing mental arithmetic to increase sympathetic activity.
Functional Electrical Stimulation
The participant will have their quadriceps passively contracted using mild electrical stimulation for approximately 30 seconds prior to standing.
Functional Electrical Stimulation
A mild electrical stimulus to passively induce a leg muscle contraction with minimal sympathetic activation.
Interventions
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Physical Counter-maneuver
Physical counter-maneuver targeted at minimizing the large drop in BP seen in IOH patients.
Stress Test
Stress test involving submerging your hand in ice water or performing mental arithmetic to increase sympathetic activity.
Functional Electrical Stimulation
A mild electrical stimulus to passively induce a leg muscle contraction with minimal sympathetic activation.
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* 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
* Sustained orthostatic hypotension past 3 minutes of standing
* Pregnant
18 Years
50 Years
ALL
Yes
Sponsors
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University of Calgary
OTHER
Responsible Party
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Principal Investigators
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Satish R Raj, MD, MSCI
Role: PRINCIPAL_INVESTIGATOR
University of Calgary
Locations
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University of Calgary
Calgary, Alberta, Canada
Countries
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References
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da Silva RM. Syncope: epidemiology, etiology, and prognosis. Front Physiol. 2014 Dec 8;5:471. doi: 10.3389/fphys.2014.00471. eCollection 2014.
McJunkin B, Rose B, Amin O, Shah N, Sharma S, Modi S, Kemper S, Yousaf M. Detecting initial orthostatic hypotension: a novel approach. J Am Soc Hypertens. 2015 May;9(5):365-9. doi: 10.1016/j.jash.2015.02.006. Epub 2015 Feb 13.
Eser I, Khorshid L, Gunes UY, Demir Y. The effect of different body positions on blood pressure. J Clin Nurs. 2007 Jan;16(1):137-40. doi: 10.1111/j.1365-2702.2005.01494.x.
Wieling W, Krediet CT, van Dijk N, Linzer M, Tschakovsky ME. Initial orthostatic hypotension: review of a forgotten condition. Clin Sci (Lond). 2007 Feb;112(3):157-65. doi: 10.1042/CS20060091.
Stewart JM, Clarke D. "He's dizzy when he stands up": an introduction to initial orthostatic hypotension. J Pediatr. 2011 Mar;158(3):499-504. doi: 10.1016/j.jpeds.2010.09.004. No abstract available.
Stewart JM. Mechanisms of sympathetic regulation in orthostatic intolerance. J Appl Physiol (1985). 2012 Nov;113(10):1659-68. doi: 10.1152/japplphysiol.00266.2012. Epub 2012 Jun 7.
Tschakovsky ME, Matusiak K, Vipond C, McVicar L. Lower limb-localized vascular phenomena explain initial orthostatic hypotension upon standing from squat. Am J Physiol Heart Circ Physiol. 2011 Nov;301(5):H2102-12. doi: 10.1152/ajpheart.00571.2011. Epub 2011 Aug 19.
Wieling W, van Dijk N, Thijs RD, de Lange FJ, Krediet CT, Halliwill JR. Physical countermeasures to increase orthostatic tolerance. J Intern Med. 2015 Jan;277(1):69-82. doi: 10.1111/joim.12249. Epub 2014 May 5. No abstract available.
Krediet CT, Go-Schon IK, Kim YS, Linzer M, Van Lieshout JJ, Wieling W. Management of initial orthostatic hypotension: lower body muscle tensing attenuates the transient arterial blood pressure decrease upon standing from squatting. Clin Sci (Lond). 2007 Nov;113(10):401-7. doi: 10.1042/CS20070064.
van Twist DJL, Dinh T, Bouwmans EME, Kroon AA. Initial orthostatic hypotension among patients with unexplained syncope: An overlooked diagnosis? Int J Cardiol. 2018 Nov 15;271:269-273. doi: 10.1016/j.ijcard.2018.05.043.
Sheikh NA, Phillips AA, Ranada S, Lloyd M, Kogut K, Bourne KM, Jorge JG, Lei LY, Sheldon RS, Exner DV, Runte M, Raj SR. Mitigating Initial Orthostatic Hypotension: Mechanistic Roles of Muscle Contraction Versus Sympathetic Activation. Hypertension. 2022 Mar;79(3):638-647. doi: 10.1161/HYPERTENSIONAHA.121.18580. Epub 2022 Jan 6.
Other Identifiers
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REB19-0792
Identifier Type: -
Identifier Source: org_study_id
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