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When an individual with Postural Tachycardia Syndrome (POTS) stands up, their heart rate increases significantly (>30BPM) and they may experience symptoms such as lightheadedness, dizziness, shortness of breath, nausea and mental confusion.
One commonly prescribed treatment for POTS is compression garments. Compression garments squeeze veins to help return blood back to the heart, which may decrease heart rate and symptoms on standing. However, there is little research about the effectiveness of compression in adults with POTS.
In this study, the investigators will use the Lifewrap garment, which compresses the abdomen, pelvis and lower extremities, to evaluate the effectiveness of compression in POTS. The investigators will use a head up tilt (HUT) which will simulate standing. The study participant will participate in 4x 10 minute HUTs wearing 4 different compression configurations:
The investigators hypothesize that with full compression, the participant's heart rate increase from lying down to upright will be lower than when they are not wearing any compression. The investigators will also ask the participant about their symptoms when they are upright.
The results of this study could demonstrate the potential benefits of compression and what configuration is most effective. These findings could rapidly translate to the clinical setting, providing improved care.
Postural Tachycardia Syndrome (POTS) is a chronic form of orthostatic intolerance marked by a significant and sustained increase in heart rate (HR) upon positional change from supine to standing (>30 beats/min [bpm]) in the absence of orthostatic hypotension (<20/10 mmHg decrease). Symptoms must be present for >6 months and other causes of orthostatic tachycardia must be ruled out. Individuals with POTS report orthostatic symptoms including palpitations, lightheadedness, and mental clouding, which improve on recumbence. The vast majority of individuals diagnosed with POTS are women age 13-50 years.
Upon standing, approximately 500 mL of blood immediately redistributes from the thorax down to the abdomen, buttocks and legs. This leads to sympathetic activation as the baroreceptors sense less pressure. In a healthy individual, HR initially increases 10-20 bpm, and the systolic blood pressure (BP) decreases by approximately 5 mmHg. However, in an individual with POTS, this compensatory mechanism is impaired and HR will increase by >30 bpm and remain at this elevated rate for the duration of standing. In some individuals with POTS, upon standing cerebral blood flow velocity decreases. In other individuals, oscillation of cerebral blood flow due to failure of cerebral autoregulatory mechanisms is observed.
Current treatment of POTS involves pharmacological and non-pharmacological intervention including salt and fluid loading, exercise, and physical countermanuevers. There are no approved medications for use in POTS and all use is off label. Compression garments are also often prescribed. Abdominal/lower extremity compression garments provide pressure to the blood vessels in the legs, thighs and abdomen which can minimize blood pooling and lead to improved blood return to the heart. One such garment is the Lifewrap Non-pneumatic AntiShock garment (NASG), indicated in post-partum hypovolemia.
A pediatric study (n=20) found that orthostatic tachycardia and symptoms were decreased during head up tilt (HUT), with the use of a different NASG compression garment vs. no compression. However, there is no data to validate the efficacy of compression in adults POTS, and also no data to determine which type of compression is most beneficial (e.g. lower leg only, abdomen only, combination).
The investigators hypothesize that the use of the Lifewrap NASG compression garment in a fully applied configuration will decrease orthostatic tachycardia and orthostatic symptoms during a 10 minute HUT vs. no compression garment. The investigators will complete a 4-way randomized crossover study of HUTs with compression applied by the LifeWrap NSAG in at attempt to demonstrate decreased orthostatic tachycardia and increased orthostatic tolerance in individuals with POTS. If successful, this study could provide needed evidence that compression in POTS is a successful non-pharmacological treatment modality, and as well, what type of compression is the most beneficial to patients with this syndrome. These findings could rapidly translate to the clinical setting and improve patient care.
The study participant will complete 4x 10min HUTs during a single study day. There will be 4 compression conditions based on strap configuration of the Lifewrap garment: (1) full abdominal and lower extremity compression, (2) abdominal only compression, (3) lower extremity only compression and (4) no compression. A pressure sensor will used to measure the magnitude of compression pressure applied. The study will be conducted on a tilt table in a human physiology research and procedure room. Each intervention phase in the protocol will involve a supine baseline assessment period of 10 minutes followed by a 10 min HUT (80 degrees). There will be a 20 min recovery periods between each HUT. The study will take approximately 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 a finger volume clamp method (Nexfin, Edwards Lifesciences) and calibrated with intermittent brachial cuff measurements (Vital-Guard 450C Patient Care Monitor, IVY Medical). From the continuous BP waveform, the investigators can obtain an estimate of stroke volume, cardiac output, and systemic vascular resistance (Modelflow). Middle cerebral blood flow velocity will be assessed using transcranial doppler.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Full Compression | Experimental | The LifeWrap compression garment will be fully secured with all straps. |
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| Abdominal and Pelvic Compression | Experimental | The Lifewrap compression garment abdominal, pelvic and upper thigh straps only will be secured. |
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| Lower Limb Compression | Experimental | The Lifewrap compression garment calf and ankle straps only will be secured. |
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| No Compression | No Intervention | None of the LifeWrap compression garment straps will be secured. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| LifeWrap Compression Garment | Device | Non-Pneumatic Anti-Shock (NASG) compression garment comprised of neoprene with velcro closures. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Orthostatic Heart Rate (HR) Change | The primary outcome measure will be the magnitude of HR change from supine to HUT (max HR between 5-10 min of HUT) for each study arm. | Maximum HR between 5-10min HUT MINUS the baseline (pre-tilt) HR |
| Measure | Description | Time Frame |
|---|---|---|
| Maximum Upright Heart Rate | The maximum heart rate during minutes 5-10 of each HUT. The maximum heart rate during each of the study arms will be compared. | During minutes 5-10 of the HUT |
| Differences in Vanderbilt Orthostatic Symptom Score (VOSS) Symptom Rating |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Satish R Raj, MD, MSCI | University of Calgary | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Unversity of Calgary | Calgary | Alberta | Canada |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 33478652 | Derived | Bourne KM, Sheldon RS, Hall J, Lloyd M, Kogut K, Sheikh N, Jorge J, Ng J, Exner DV, Tyberg JV, Raj SR. Compression Garment Reduces Orthostatic Tachycardia and Symptoms in Patients With Postural Orthostatic Tachycardia Syndrome. J Am Coll Cardiol. 2021 Jan 26;77(3):285-296. doi: 10.1016/j.jacc.2020.11.040. |
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This was a randomized cross-over trial. Participants were assigned to receive the 4 compressions interventions in a randomized order. There were a total of 24 potential sequence orders of the compression interventions.
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| ID | Title | Description |
|---|---|---|
| FG000 | 4 Compression Interventions in Randomized Order | Participants completed all 4 compression garment interventions in a random order. There were a total of 24 possible intervention orders. The 4 compression interventions were: Full Compression, Abdominal and Pelvic Compression, Lower Limb Compression and No Compression. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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| ID | Title | Description |
|---|---|---|
| BG000 | Full Compression | The LifeWrap compression garment will be fully secured with all straps. LifeWrap Compression Garment: Non-Pneumatic Anti-Shock (NASG) compression garment comprised of neoprene with velcro closures. |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Orthostatic Heart Rate (HR) Change | The primary outcome measure will be the magnitude of HR change from supine to HUT (max HR between 5-10 min of HUT) for each study arm. | This was a crossover trial. A total of 30 participants were analyzed. | Posted | Mean | Standard Deviation | beats per minute | Maximum HR between 5-10min HUT MINUS the baseline (pre-tilt) HR |
|
This was a half day study and there was no ongoing follow up.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Full Compression | The LifeWrap compression garment will be fully secured with all straps. LifeWrap Compression Garment: Non-Pneumatic Anti-Shock (NASG) compression garment comprised of neoprene with velcro closures. |
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This was a proof of principle study. The garment used is not one that a typical patient would use in their day to day lives. The use of "real-world" garments requires further testing.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Satish R. Raj | University of Calgary | 403-210-6152 | satish.raj@ucalgary.ca |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Jan 26, 2018 | Mar 12, 2018 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D054972 | Postural Orthostatic Tachycardia Syndrome |
| D001342 | Autonomic Nervous System Diseases |
| ID | Term |
|---|---|
| D054971 | Orthostatic Intolerance |
| D054969 | Primary Dysautonomias |
| D009422 | Nervous System Diseases |
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There will be 4 compression conditions based on strap configuration of the Lifewrap garment: full abdominal and lower extremity compression, abdominal only compression, lower extremity only compression and no compression. The order of these interventions will be randomized.
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Subjective symptom scoring as reported by participant during each study arm. The VOSS evaluates 9 symptoms on a 0 to 10 scale with 0 being no symptom to 10 being worst ever symptom. The total score ranges from 0-90, with a higher score being more severe symptoms. The 9 symptoms are mental clouding, blurred vision, shortness of breath, rapid heartbeat, tremulousness, chest discomfort, headache, lightheadedness, and nausea. The participant's VOSS score will be compared across the 4 arms of this study. The VOSS score has been previously used in multiple publications |
| After t=10 of the 10min HUT (or sooner if HUT has to be terminated early due to symptoms) |
| Change in Systolic Blood Pressure (SBP) | Change in continuous systolic blood pressure between supine and HUT during each study arm. | During the baseline before the HUT and the SBP correlating with the maximum HR during 5-10 min HUT, recorded at 1 min intervals. |
| Changes in Stroke Volume | Change in Stroke Volume from supine to HUT in each of the study arms. | During the baseline before the HUT and the SV correlating with the maximum HR during 5-10 min HUT, recorded at 1 min intervals. |
| Change in Cardiac Output (CO) | Change in Cardiac Output from supine to HUT in each of the study arms. | During the baseline before the HUT and the CO correlating with the maximum HR during 5-10 min HUT, recorded at 1 min intervals. |
| Change in Systemic Vascular Resistance (SVR) | Change in Systemic Vascular Resistance from supine to HUT in each of the study arms. | During the baseline before the HUT and the SVRcorrelating with the maximum HR during 5-10 min HUT, recorded at 1min intervals. |
| Change in Cerebral Blood Flow Velocity (CBFV) | Change in cerebral blood flow from supine to HUT in each of the study arms. | During the baseline before the HUT and the CBFV correlating with the maximum HR during 5-10 min HUT, recorded at 1 min intervals. |
| years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race and Ethnicity Not Collected | Race and Ethnicity were not collected from any participant. | Count of Participants | Participants |
|
| Region of Enrollment | Count of Participants | Participants |
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| Body Mass Index (BMI) | Mean | Standard Deviation | kg/m^2 |
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The Lifewrap compression garment abdominal, pelvic and upper thigh straps only will be secured.
| OG002 | Lower Limb Compression | The Lifewrap compression garment calf and ankle straps only will be secured. |
| OG003 | No Compression | None of the LifeWrap compression garment straps will be secured. |
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| Secondary | Maximum Upright Heart Rate | The maximum heart rate during minutes 5-10 of each HUT. The maximum heart rate during each of the study arms will be compared. | This was a crossover trial. A total of 30 participants were analyzed. | Posted | Mean | Standard Deviation | beats per minute (bpm) | During minutes 5-10 of the HUT |
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| Secondary | Differences in Vanderbilt Orthostatic Symptom Score (VOSS) Symptom Rating | Subjective symptom scoring as reported by participant during each study arm. The VOSS evaluates 9 symptoms on a 0 to 10 scale with 0 being no symptom to 10 being worst ever symptom. The total score ranges from 0-90, with a higher score being more severe symptoms. The 9 symptoms are mental clouding, blurred vision, shortness of breath, rapid heartbeat, tremulousness, chest discomfort, headache, lightheadedness, and nausea. The participant's VOSS score will be compared across the 4 arms of this study. The VOSS score has been previously used in multiple publications | This was a crossover trial. A total of 30 participants were analyzed. | Posted | Mean | Standard Deviation | units on a scale | After t=10 of the 10min HUT (or sooner if HUT has to be terminated early due to symptoms) |
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| Secondary | Change in Systolic Blood Pressure (SBP) | Change in continuous systolic blood pressure between supine and HUT during each study arm. | This was a crossover trial. A total of 29 participants were analyzed. | Posted | Mean | Standard Deviation | mmHg | During the baseline before the HUT and the SBP correlating with the maximum HR during 5-10 min HUT, recorded at 1 min intervals. |
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| Secondary | Changes in Stroke Volume | Change in Stroke Volume from supine to HUT in each of the study arms. | This was a crossover trial. A total of 29 participants were analyzed. | Posted | Mean | Standard Deviation | mL | During the baseline before the HUT and the SV correlating with the maximum HR during 5-10 min HUT, recorded at 1 min intervals. |
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| Secondary | Change in Cardiac Output (CO) | Change in Cardiac Output from supine to HUT in each of the study arms. | This was a crossover trial. A total of 29 participants were analyzed. | Posted | Mean | Standard Deviation | L/min | During the baseline before the HUT and the CO correlating with the maximum HR during 5-10 min HUT, recorded at 1 min intervals. |
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| Secondary | Change in Systemic Vascular Resistance (SVR) | Change in Systemic Vascular Resistance from supine to HUT in each of the study arms. | This was a crossover trial. A total of 29 participants were analyzed. | Posted | Mean | Standard Deviation | dyne*s/cm^5 | During the baseline before the HUT and the SVRcorrelating with the maximum HR during 5-10 min HUT, recorded at 1min intervals. |
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| Secondary | Change in Cerebral Blood Flow Velocity (CBFV) | Change in cerebral blood flow from supine to HUT in each of the study arms. | Not Posted | During the baseline before the HUT and the CBFV correlating with the maximum HR during 5-10 min HUT, recorded at 1 min intervals. | Participants |
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| 32 |
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| 32 |
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| 32 |
| EG001 | Abdominal and Pelvic Compression | The Lifewrap compression garment abdominal, pelvic and upper thigh straps only will be secured. | 0 | 32 | 0 | 32 | 0 | 32 |
| EG002 | Lower Limb Compression | The Lifewrap compression garment calf and ankle straps only will be secured. | 0 | 32 | 0 | 32 | 0 | 32 |
| EG003 | No Compression | None of the LifeWrap compression garment straps will be secured. | 0 | 32 | 0 | 32 | 0 | 32 |
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