SVC Assessment for POTS
Recruiting in Palo Alto (17 mi)
Age: 18 - 65
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Vanderbilt University Medical Center
Must not be taking: Acetaminophen, Statins, Corticosteroids, others
Disqualifiers: Heart problems, Diabetes, Pregnancy, others
Prior Safety Data
Trial Summary
What is the purpose of this trial?This trial will study how a sugary drink affects blood vessels in the stomach area of POTS patients. It aims to understand if this causes their symptoms like dizziness and rapid heartbeat. The study will compare these patients to healthy individuals to find out why they react differently.
Will I have to stop taking my current medications?
The trial does not specify if you need to stop taking your current medications, but it excludes those on chronic medications and certain specific drugs like acetaminophen and statins. It's best to discuss your current medications with the trial coordinators.
What data supports the effectiveness of the treatment Measurement of Splanchnic venous capacitance (SVC) for POTS?
Research shows that patients with POTS often have increased blood flow and volume in the splanchnic region (the area around the stomach and intestines), which can affect blood pressure and heart rate. By measuring and potentially managing this splanchnic blood flow, the treatment may help address some of the symptoms associated with POTS.
12345Is the SVC Assessment for POTS safe for humans?
The research does not provide specific safety data for the SVC Assessment for POTS, but related studies on splanchnic nerve modulation in heart failure patients suggest it is generally safe, with some changes in blood pressure and heart function observed.
12367How does the SVC treatment for POTS differ from other treatments?
The SVC treatment for POTS is unique because it focuses on measuring changes in the splanchnic (abdominal) blood vessels' capacity and pressure-volume relationship using a noninvasive imaging technique called equilibrium blood pool scintigraphy (EBPS). This approach is different from typical treatments that may not specifically target or measure these vascular changes.
89101112Eligibility Criteria
This trial is for adults aged 18-50 with Postural Tachycardia Syndrome (POTS) who experience symptoms like dizziness after meals. Participants should have a BMI of 18.5 to 29.9 and, if female and pre-menopausal, regular menstrual cycles. Exclusions include heart conditions, seizures, neuropathy, pregnancy, substance abuse, certain chronic diseases or medications.Inclusion Criteria
I am between 18 and 50 years old.
I am a pre-menopausal woman with a regular menstrual cycle.
I have been diagnosed with POTS and feel faint after eating.
+5 more
Exclusion Criteria
I have rheumatoid arthritis.
I regularly use acetaminophen.
I am taking statins for high cholesterol.
+20 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
1 visit
1 visit (in-person)
Baseline
Includes Tilt table test, Oral glucose tolerance test (OGTT), Splanchnic venous capacitance measurements
1 visit
1 visit (in-person)
Treatment
Randomization to saline versus GIP antagonist infusion, measurement of splanchnic venous capacitance and superior mesenteric arterial flow
3 hours
2 visits (in-person)
Follow-up
Participants are monitored for safety and effectiveness after treatment
4 weeks
Participant Groups
The study measures the Splanchnic venous capacitance (SVC) in POTS patients compared to healthy controls to see if SVC increases more in POTS patients after eating glucose-rich foods causing worse symptoms.
2Treatment groups
Active Control
Placebo Group
Group I: Changes in Splanchnic venous capacitance(SVC) before and after a 75-g oral glucose challengeActive Control2 Interventions
To compare and measure changes in splanchnic venous capacitance and superior mesenteric arterial flow before and after a 75-g oral glucose challenge during supine and 45-degree head-up tilt positions (orthostatic challenge) for up to 3 hr. between participants with POTS (Postural Tachycardia Syndrome) and Healthy Control group
Various GIP hormones especially GLP-1, GLP-2, glucagon, and other GI hormones before and after a 75-gram oral glucose at different timepoints through out 3 hours of the study visit
Group II: Effect of GIP antagonist GIP(3-30)NH2 Vs Saline on splanchnic venous capacitance on POTS patientsPlacebo Group2 Interventions
POTS patients who participated in Aim 1, will be and randomized to either saline versus GIP antagonist (GIP(3-30)NH2) in Visit 2.
The changes in their splanchnic venous capacitance and superior mesenteric arterial flow will be measured, before and after a 75-g oral glucose challenge during supine and 45-degree head-up tilt positions (orthostatic challenge) for up to 3 hr.
Notably, changes in venous capacitance will be assessed using segmental impedance to measure the effect of graded positive airway pressure (CPAP) on splanchnic blood volume.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Vanderbilt University Medical CenterNashville, TN
Loading ...
Who Is Running the Clinical Trial?
Vanderbilt University Medical CenterLead Sponsor
National Heart, Lung, and Blood Institute (NHLBI)Collaborator
References
Splanchnic hyperemia and hypervolemia during Valsalva maneuver in postural tachycardia syndrome. [2020]Prior work demonstrated dependence of the change in blood pressure during the Valsalva maneuver (VM) on the extent of thoracic hypovolemia and splanchnic hypervolemia. Thoracic hypovolemia and splanchnic hypervolemia characterize certain patients with postural tachycardia syndrome (POTS) during orthostatic stress. These patients also experience abnormal phase II hypotension and phase IV hypertension during VM. We hypothesize that reduced splanchnic arterial resistance explains aberrant VM results in these patients. We studied 17 POTS patients aged 15-23 yr with normal resting peripheral blood flow by strain gauge plethysmography and 10 comparably aged healthy volunteers. All had normal blood volumes by dye dilution. We assessed changes in estimated thoracic, splanchnic, pelvic-thigh, and lower leg blood volume and blood flow by impedance plethysmography throughout VM performed in the supine position. Baseline splanchnic blood flow was increased and calculated arterial resistance was decreased in POTS compared with control subjects. Splanchnic resistance decreased and flow increased in POTS subjects, whereas splanchnic resistance increased and flow decreased in control subjects during stage II of VM. This was associated with increased splanchnic blood volume, decreased thoracic blood volume, increased heart rate, and decreased blood pressure in POTS. Pelvic and leg resistances were increased above control and remained so during stage IV of VM, accounting for the increased blood pressure overshoot in POTS. Thus splanchnic hyperemia and hypervolemia are related to excessive phase II blood pressure reduction in POTS despite intense peripheral vasoconstriction. Factors other than autonomic dysfunction may play a role in POTS.
Persistent splanchnic hyperemia during upright tilt in postural tachycardia syndrome. [2020]Previous investigations have allowed for stratification of patients with postural tachycardia syndrome (POTS) on the basis of peripheral blood flow. One such subset, comprising "normal-flow POTS" patients, is characterized by normal peripheral resistance and blood volume in the supine position but thoracic hypovolemia and splanchnic blood pooling in the upright position. We studied 32 consecutive 14- to 22-yr-old POTS patients comprising 13 with low-flow POTS, 14 with normal-flow POTS, and 5 with high-flow POTS and 12 comparably aged healthy volunteers. We measured changes in impedance plethysmographic (IPG) indexes of blood volume and blood flow within thoracic, splanchnic, pelvic (upper leg), and lower leg regional circulations in the supine posture and during incremental tilt to 20 degrees, 35 degrees, and 70 degrees. We validated IPG measures of thoracic and splanchnic blood flow against indocyanine green dye-dilution measurements. We validated IPG leg blood flow against venous occlusion plethysmography. Control subjects developed progressive vasoconstriction with incremental tilt. Splanchnic blood flow was increased in the supine position in normal-flow POTS, despite marked peripheral vasoconstriction, and did not change during incremental tilt, producing progressive splanchnic hypervolemia. Absolute hypovolemia was present in low-flow POTS, all supine flows and volumes were reduced, there was no vasoconstriction with tilt in all segments, and segmental volumes tended to increase uniformly throughout tilt. Lower body (pelvic and leg) flows were increased in high-flow POTS at all angles, with consequent lower body hypervolemia during tilt. Our main finding is selective and maintained orthostatic splanchnic vasodilation in normal-flow POTS, despite marked peripheral vasoconstriction in these same patients. Local splanchnic vasoregulatory factors may counteract vasoconstriction and venoconstriction in these patients. Lower body vasoconstriction in high-flow POTS was abnormal, and vasoconstriction in low-flow POTS was sustained at initially elevated supine levels.
Postural hypocapnic hyperventilation is associated with enhanced peripheral vasoconstriction in postural tachycardia syndrome with normal supine blood flow. [2020]Previous investigations have demonstrated a subset of postural tachycardia syndrome (POTS) patients characterized by normal peripheral resistance and blood volume while supine but thoracic hypovolemia and splanchnic blood pooling while upright secondary to splanchnic hyperemia. Such "normal-flow" POTS patients often demonstrate hypocapnia during orthostatic stress. We studied 20 POTS patients (14-23 yr of age) and compared them with 10 comparably aged healthy volunteers. We measured changes in heart rate, blood pressure, heart rate and blood pressure variability, arm and leg strain-gauge occlusion plethysmography, respiratory impedance plethysmography calibrated against pneumotachography, end-tidal partial pressure of carbon dioxide (Pet(CO2)), and impedance plethysmographic indexes of blood volume and blood flow within the thoracic, splanchnic, pelvic (upper leg), and lower leg regional circulations while supine and during upright tilt to 70 degrees. Ten POTS patients demonstrated significant hyperventilation and hypocapnia (POTS(HC)) while 10 were normocapnic with minimal increase in postural ventilation, comparable to control. While relative splanchnic hypervolemia and hyperemia occurred in both POTS groups compared with controls, marked enhancement in peripheral vasoconstriction occurred only in POTS(HC) and was related to thoracic blood flow. Variability indexes suggested enhanced sympathetic activation in POTS(HC) compared with other subjects. The data suggest enhanced cardiac and peripheral sympathetic excitation in POTS(HC).
Regional blood volume and peripheral blood flow in postural tachycardia syndrome. [2020]Variants of postural tachycardia syndrome (POTS) are associated with increased ["high-flow" POTS (HFP)], decreased ["low-flow" POTS (LFP)], and normal ["normal-flow" POTS (NFP)] blood flow measured in the lower extremities while subjects were in the supine position. We propose that postural tachycardia is related to thoracic hypovolemia during orthostasis but that the patterns of peripheral blood flow relate to different mechanisms for thoracic hypovolemia. We studied 37 POTS patients aged 14-21 yr: 14 LFP, 15 NFP, and 8 HFP patients and 12 healthy control subjects. Peripheral blood flow was measured in the supine position by venous occlusion strain-gauge plethysmography of the forearm and calf to subgroup patients. Using indocyanine green techniques, we showed decreased cardiac index (CI) and increased total peripheral resistance (TPR) in LFP, increased CI and decreased TPR in HFP, and unchanged CI and TPR in NFP while subjects were supine compared with control subjects. Blood volume tended to be decreased in LFP compared with control subjects. We used impedance plethysmography to assess regional blood volume redistribution during upright tilt. Thoracic blood volume decreased, whereas splanchnic, pelvic, and leg blood volumes increased, for all subjects during orthostasis but were markedly lower than control for all POTS groups. Splanchnic volume was increased in NFP and LFP. Pelvic blood volume was increased in HFP only. Calf volume was increased above control in HFP and LFP. The results support the hypothesis of (at least) three pathophysiologic variants of POTS distinguished by peripheral blood flow related to characteristic changes in regional circulations. The data demonstrate enhanced thoracic hypovolemia during upright tilt and confirm that POTS is related to inadequate cardiac venous return during orthostasis.
Vascular perturbations in the chronic orthostatic intolerance of the postural orthostatic tachycardia syndrome. [2017]Chronic orthostatic intolerance is often related to the postural orthostatic tachycardia syndrome (POTS). POTS is characterized by upright tachycardia. Understanding of its pathophysiology remains incomplete, but edema and acrocyanosis of the lower extremities occur frequently. To determine how arterial and venous vascular properties account for these findings, we compared 13 patients aged 13-18 yr with 10 normal controls. Heart rate and blood pressure were continuously recorded, and strain-gauge plethysmography was used to measure forearm and calf blood flow, venous compliance, and microvascular filtration while the subject was supine and to measure calf blood flow and calf size change during head-up tilt. Resting venous pressure was higher in POTS compared with control (16 vs. 10 mmHg), which gave the appearance of decreased compliance in these patients. The threshold for edema formation decreased in POTS patients compared with controls (8.3 vs. 16.3 mmHg). With tilt, early calf blood flow increased in POTS patients (from 3.4 +/- 0.9 to 12.6 +/- 2.3 ml. 100 ml(-1). min(-1)) but did not increase in controls. Calf volume increased twice as much in POTS patients compared with controls over a shorter time of orthostasis. The data suggest that resting venous pressure is higher and the threshold for edema is lower in POTS patients compared with controls. Such findings make the POTS patients particularly vulnerable for edema fluid collection. This may signify a redistribution of blood to the lower extremities even while supine, accounting for tachycardia through vagal withdrawal.
Mechanisms of tilt-induced vasovagal syncope in healthy volunteers and postural tachycardia syndrome patients without past history of syncope. [2023]Upright tilt table testing has been used to test for vasovagal syncope (VVS) but can result in "false positives" in which tilt-induced fainting (tilt+) occurs in the absence of real-world fainting. Tilt+ occurs in healthy volunteers and in patients with postural tachycardia syndrome (POTS) and show enhanced susceptibility to orthostatic hypotension. We hypothesized that the mechanisms for hypotensive susceptibility differs between tilt+ healthy volunteers (Control-Faint (N = 12)), tilt+ POTS patients (POTS-Faint (N = 12)) and a non-fainter control group of (Control-noFaint) (N = 10). Subjects were studied supine and during 70° upright tilt while blood pressure (BP), cardiac output (CO), and systemic vascular resistance (SVR), were measured continuously. Impedance plethysmography estimated regional blood volumes, flows, and vascular resistance. Heart rate was increased while central blood volume was decreased in both Faint groups. CO increased in Control-Faint because of reduced splanchnic vascular resistance; splanchnic pooling was similar to Control-noFaint. Splanchnic blood flow in POTS-Faint decreased and resistance increased similar to Control-noFaint but splanchnic blood volume was markedly increased. Decreased SVR and splanchnic arterial vasoconstriction is the mechanism for faint in Control-Faint. Decreased CO caused by enhanced splanchnic pooling is the mechanism for faint in POTS-Faint. We propose that intrahepatic resistance is increased in POTS-Faint resulting in pooling and that both intrahepatic resistance and splanchnic arterial vasoconstriction are reduced in Control-Faint resulting in increased splanchnic blood flow and reduced splanchnic resistance.
Splanchnic Nerve Modulation Effects on Surrogate Measures of Venous Capacitance. [2023]Background Splanchnic nerve modulation (SNM) is an emerging procedure to reduce cardiac filling pressures in heart failure. Although the main contributor to reduction in cardiac preload is thought to be increased venous capacitance in the splanchnic circulation, supporting evidence is limited. We examined changes in venous capacitance surrogates pre- and post-SNM. Methods and Results This is a prespecified analysis of a prospective, open-label, single-arm interventional study evaluating the effects of percutaneous SNM with ropivacaine in chronic heart failure with elevated filling pressures at rest and with exercise. Patients underwent cardiopulmonary exercise testing with invasive hemodynamic assessment pre- and post-SNM. Blood pressure changes with modified Valsalva maneuver and hemoconcentration, pre- and post-SNM were compared using a repeated measures model. Inferior vena cava diameter and collapsibility (>50% decrease in size with inspiration), and presence of bendopnea pre- and post-SNM were also compared. Fifteen patients undergoing SNM (age 58 years, 47% women, 93% with left ventricular ejection fraction ≤35%) were included. After SNM, changes in systolic blood pressure during Valsalva (peak-to-trough) were greater (41 versus 48 mm Hg, P=0.025). Exercise-induced hemoconcentration was unchanged (0.63 versus 0.43 g/dL, P=0.115). Inferior vena cava diameter was reduced (1.59 versus 1.30 cm, P=0.034) with higher collapsibility (33% versus 73%, P=0.014). Bendopnea was less (47% versus 13%, P=0.025). Conclusions SNM resulted in increased venous capacitance, associated decreased cardiac preload, and decreased bendopnea. Minimally invasive measures of venous capacitance could serve as markers of successful SNM. Long-term effects of SNM on venous capacitance warrant further investigation for heart failure management. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT03453151.
Assessment of the splanchnic vascular capacity and capacitance using quantitative equilibrium blood-pool scintigraphy. [2015]A series of human and animal experiments were carried out to assess the usefulness of equilibrium blood pool scintigraphy (EBPS) to study acute changes of the splanchnic vascular capacity and the splanchnic vascular pressure-volume (P-V) relationship. Corrected regional abdominal count rate changes, before and after various pharmacologic interventions, were used to assess regional splanchnic vascular volume changes. Animals were instrumented to manipulate and record splanchnic venous pressures. In patients, splanchnic vascular capacity increased by 5.2 +/- 6.9% (p less than 0.001) after 0.6 mg sublingual nitroglycerin while no significant change was noted after sugar pills (0.9 +/- 5.2%, p greater than 0.3). In dogs, splanchnic vascular capacity decreased by a mean of 16% during infusion of angiotensin (p less than 0.001) and increased by a mean of 32% during infusion of nitroprusside (p less than 0.001). The splanchnic vascular P-V curve was shifted rightwards during nitroglycerin administration. Thus, using the radionuclide technique we detected the expected qualitative and quantitative shifts in splanchnic capacity and capacitance. We conclude that EBPS is a useful method to assess acute changes of 1) the splanchnic vascular P-V relationship, in invasive animal studies, and 2) the splanchnic vascular capacity in noninvasive human and animal studies.
Responses of abdominal vascular capacitance to stimulation of splachnic nerves. [2017]In chloralose-anesthetized dogs the abdominal circulation was vascularly isolated without opening the abdominal cavity. The region was perfused at constant flow through the aorta and drained at constant pressure from the inferior vena cava. Changes in resistance were calculated from changes in perfusion pressure and changes in capacitance were calculated by integrating changes in venous outflow. Stimulation of both splanchnic nerves at 20 Hz increased resistance by 135% and reduced capacitance by 7.20 ml kg-1. The capacitance responses at 1 and 2 Hz (3.42 and 5.43 ml kg-1) were 48 and 67% of the responses at 20 Hz, However, the resistance responses at 1 and 2 Hz (14 and 31% increase) were only 12 and 26% of the responses at 20 Hz. After occlusion of the splenic pedicle, capacitance responses were reduced by about 40%. Although changes in inferior vena caval pressure changed the volume of blood in the abdomen by 0.92 ml kg-1 cmH2O-1, the responses to stimulation were relatively constant in any one animal at constant venous pressures between 5 and 15 cmH2O.
Endotoxemia alters splanchnic capacitance. [2019]The splanchnic circulation constitutes a major portion of the total capacitance vasculature and may affect venous return and subsequently cardiac output during low output states. This study assessed the effects of rapid (10 microg/kg over 5 min) and slow (10 microg/kg over 60 min) induction of endotoxin (Escherichia coli) shock on splanchnic blood volume in 8 farm swine. Blood volume was measured by using Tc99m-labeled erythrocytes and radionuclide imaging. Baseline arterial pressure (MAP), central venous pressure (CVP), and liver, splenic, mesenteric and total splanchnic volumes were stable during the 30-min baseline. Approximately 30 min after the rapid endotoxin infusion, splenic volume decreased by 45%, whereas liver volume increased by 40% and MAP decreased by 60% (P
Global sensitivity analysis of hepatic venous pressure gradient (HVPG) measurement with a stochastic computational model of the hepatic circulation. [2019]Hepatic venous pressure gradient (HVPG) is a widely employed surrogate of portal pressure gradient (PPG) in the diagnosis of portal hypertension (PHT). However, little is known about how HVPG measurement is affected by the complex vascular changes associated with PHT. In this study, we employed a computational method to quantitatively evaluate the sensitivity of HVPG measurement to various vascular factors involved in the development of sinusoidal PHT, aiming to provide a theoretical reference to guide the clinical application of HVPG measurement. The method consisted of developing a lumped-parameter model of the hepatic circulation to simulate HVPG measurement, stochastic parameter sampling used to represent a wide range of pathological conditions, and global sensitivity analysis performed to identify factors that dominate the accuracy of HVPG measurement. The major findings included 1) presinusoidal portal vascular resistance (Rpxs) and splanchnic vascular resistance (Rspl) were the major factors determining the relative difference (EHVPG) between HVPG and PPG; 2) hepatic arteriolar resistance and portosystemic collateral resistance had little influence on EHVPG although they relate closely to the severity of PHT; and 3) postsinusoidal vascular resistance (Rpts) only mildly affected EHVPG, despite its marked influence on HVPG and PPG. Moreover, stochastic simulations calibrated to HVPG/PPG data measured in a patient cohort revealed that misdiagnosis of clinically significant PHT with HVPG was more likely to occur in the presence of high Rspl combined with low Rpxs and Rpts. These findings suggest that understanding patient-specific vascular conditions can help to improve the application or interpretation of HVPG measurement.
Splanchnic blood flow in patients with cirrhosis and portal hypertension: investigation with duplex Doppler US. [2016]To investigate splanchnic blood flow changes in patients with hepatic cirrhosis and portal hypertension.