SVC Assessment for POTS

Overseen By Francesca Mckay, BS

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. ^{1 2 3 4 5}

Is 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. ^{1 2 3 6 7}

How 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. ^{8 9 10 11 12}

Research Team

Cyndya A Shibao, MD

Principal Investigator

Vanderbilt University Medical Center

Eligibility 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.

Exclusion Criteria

I have rheumatoid arthritis.

I regularly use acetaminophen.

I am taking statins for high cholesterol.

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

Treatment Details

Interventions

• Measurement of Splanchnic venous capacitance(SVC) (Diagnostic Test)

Trial Overview 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.

Participant Groups

Group I: Changes in Splanchnic venous capacitance(SVC) before and after a 75-g oral glucose challenge Active Control 2 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 patients Placebo Group 2 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.

Who Is Running the Clinical Trial?

Vanderbilt University Medical Center

Lead Sponsor

Trials

922

Recruited

939,000+

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials

3,987

Recruited

47,860,000+

Findings from Research

In a study of 17 patients with postural tachycardia syndrome (POTS) and 10 healthy controls, POTS patients exhibited increased splanchnic blood flow and decreased arterial resistance, which contributed to abnormal blood pressure responses during the Valsalva maneuver.

The findings suggest that splanchnic hyperemia and hypervolemia are linked to excessive blood pressure drops in POTS patients, indicating that factors beyond autonomic dysfunction may influence the condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Splanchnic hyperemia and hypervolemia during Valsalva maneuver in postural tachycardia syndrome. Stewart, JM., Medow, MS., Montgomery, LD., et al.[2020]

In a study of 32 POTS patients aged 14 to 22, normal-flow POTS patients exhibited selective splanchnic vasodilation while experiencing peripheral vasoconstriction, indicating a unique blood flow regulation mechanism in this subset.

Low-flow POTS patients showed absolute hypovolemia and no vasoconstriction during tilt, while high-flow POTS patients had increased lower body blood flow, suggesting distinct pathophysiological profiles among POTS subtypes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Persistent splanchnic hyperemia during upright tilt in postural tachycardia syndrome. Stewart, JM., Medow, MS., Glover, JL., et al.[2020]

In a study of 20 POTS patients aged 14-23, those with hypocapnia (POTS(HC)) showed significant hyperventilation and enhanced sympathetic activation compared to normocapnic POTS patients and healthy controls.

Both POTS groups exhibited splanchnic hypervolemia and hyperemia, but only the POTS(HC) group demonstrated increased peripheral vasoconstriction, indicating a distinct physiological response related to thoracic blood flow.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Postural hypocapnic hyperventilation is associated with enhanced peripheral vasoconstriction in postural tachycardia syndrome with normal supine blood flow. Stewart, JM., Medow, MS., Cherniack, NS., et al.[2020]

In a study of 37 POTS patients aged 14-21, three variants of postural tachycardia syndrome (HFP, LFP, NFP) were identified, each showing distinct patterns of blood flow and cardiac function while supine, indicating different underlying mechanisms of thoracic hypovolemia.

The research confirmed that POTS is associated with inadequate cardiac venous return during upright posture, with significant differences in blood volume redistribution among the variants, highlighting the complexity of this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Regional blood volume and peripheral blood flow in postural tachycardia syndrome. Stewart, JM., Montgomery, LD.[2020]

In patients with postural orthostatic tachycardia syndrome (POTS), resting venous pressure is significantly higher than in healthy controls, which may indicate decreased venous compliance and a greater risk for fluid accumulation in the lower extremities.

POTS patients also show a lower threshold for edema formation and an increased calf blood flow response during head-up tilt, suggesting that their vascular properties contribute to symptoms like tachycardia and edema.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vascular perturbations in the chronic orthostatic intolerance of the postural orthostatic tachycardia syndrome. Stewart, JM., Weldon, A.[2017]

In a study involving 34 participants (12 healthy volunteers with tilt-induced fainting, 12 POTS patients with tilt-induced fainting, and 10 non-fainting controls), it was found that the mechanisms causing fainting during upright tilt differ between healthy individuals and POTS patients.

Healthy volunteers (Control-Faint) faint due to decreased systemic vascular resistance and increased blood flow to the splanchnic area, while POTS patients (POTS-Faint) faint because of decreased cardiac output caused by excessive blood pooling in the splanchnic region.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mechanisms of tilt-induced vasovagal syncope in healthy volunteers and postural tachycardia syndrome patients without past history of syncope. Stewart, JM., Shaban, MA., Fialkoff, T., et al.[2023]

Splanchnic nerve modulation (SNM) significantly increased venous capacitance in patients with chronic heart failure, as evidenced by a reduction in inferior vena cava diameter and increased collapsibility after the procedure.

Post-SNM, patients experienced decreased cardiac preload and less bendopnea, indicating that SNM may effectively alleviate symptoms related to elevated filling pressures in heart failure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Splanchnic Nerve Modulation Effects on Surrogate Measures of Venous Capacitance. Kittipibul, V., Ganesh, A., Coburn, A., et al.[2023]

Equilibrium blood pool scintigraphy (EBPS) effectively measures acute changes in splanchnic vascular capacity, showing a significant increase in humans after sublingual nitroglycerin administration (5.2% increase, p < 0.001) compared to no change with a placebo.

In animal studies, EBPS demonstrated that splanchnic vascular capacity can decrease with angiotensin infusion (16% decrease, p < 0.001) and increase with nitroprusside infusion (32% increase, p < 0.001), confirming its utility in assessing the splanchnic vascular pressure-volume relationship.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessment of the splanchnic vascular capacity and capacitance using quantitative equilibrium blood-pool scintigraphy. Robinson, VJ., Smiseth, OA., Scott-Douglas, NW., et al.[2015]

In a study involving chloralose-anesthetized dogs, stimulating the splanchnic nerves at 20 Hz significantly increased vascular resistance by 135% and reduced blood capacitance by 7.20 ml/kg, indicating a strong response in abdominal circulation.

Lower stimulation frequencies (1 and 2 Hz) produced much smaller increases in resistance (14% and 31%) and reduced capacitance responses (3.42 and 5.43 ml/kg), suggesting that higher frequency stimulation is more effective for altering abdominal blood flow dynamics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Responses of abdominal vascular capacitance to stimulation of splachnic nerves. Karim, F., Hainsworth, R.[2017]

In a study involving 8 farm swine, rapid and slow induction of E. coli endotoxin shock led to significant changes in splanchnic blood volume, with rapid infusion causing a 45% decrease in splenic volume and a 40% increase in liver volume after a drop in mean arterial pressure (MAP).

The study found that endotoxin shock does not lead to pooling of blood in the splanchnic circulation; instead, it can decrease total splanchnic volume, particularly with slow infusion, indicating complex responses in blood distribution during low output states.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Endotoxemia alters splanchnic capacitance. Ujhelyi, MR., Miller, AW., Raibon, S., et al.[2019]

The study identified that presinusoidal portal vascular resistance (Rpxs) and splanchnic vascular resistance (Rspl) are the primary factors affecting the accuracy of hepatic venous pressure gradient (HVPG) measurements compared to portal pressure gradient (PPG) in diagnosing portal hypertension (PHT).

Misdiagnosis of significant PHT using HVPG is more likely when patients have high splanchnic vascular resistance combined with low presinusoidal and postsinusoidal vascular resistance, highlighting the importance of considering individual vascular conditions for accurate diagnosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Global sensitivity analysis of hepatic venous pressure gradient (HVPG) measurement with a stochastic computational model of the hepatic circulation. Wang, T., Liang, F., Zhou, Z., et al.[2019]

In a study of 20 patients with hepatic cirrhosis and portal hypertension, blood flow in the superior mesenteric artery and splenic artery was significantly higher compared to 20 healthy volunteers, indicating altered blood flow dynamics in these patients.

Increased splanchnic blood flow was primarily observed in patients with splenomegaly, suggesting that the enlargement of the spleen may be a key factor in the changes in blood flow associated with cirrhosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Splanchnic blood flow in patients with cirrhosis and portal hypertension: investigation with duplex Doppler US. Zwiebel, WJ., Mountford, RA., Halliwell, MJ., et al.[2016]

References

1. United States pubmed.ncbi.nlm.nih.gov

Splanchnic hyperemia and hypervolemia during Valsalva maneuver in postural tachycardia syndrome. [2020]

2. United States pubmed.ncbi.nlm.nih.gov

Persistent splanchnic hyperemia during upright tilt in postural tachycardia syndrome. [2020]

3. United States pubmed.ncbi.nlm.nih.gov

Postural hypocapnic hyperventilation is associated with enhanced peripheral vasoconstriction in postural tachycardia syndrome with normal supine blood flow. [2020]

4. United States pubmed.ncbi.nlm.nih.gov

Regional blood volume and peripheral blood flow in postural tachycardia syndrome. [2020]

5. United States pubmed.ncbi.nlm.nih.gov

Vascular perturbations in the chronic orthostatic intolerance of the postural orthostatic tachycardia syndrome. [2017]

6. United States pubmed.ncbi.nlm.nih.gov

Mechanisms of tilt-induced vasovagal syncope in healthy volunteers and postural tachycardia syndrome patients without past history of syncope. [2023]

7. England pubmed.ncbi.nlm.nih.gov

Splanchnic Nerve Modulation Effects on Surrogate Measures of Venous Capacitance. [2023]

8. United States pubmed.ncbi.nlm.nih.gov

Assessment of the splanchnic vascular capacity and capacitance using quantitative equilibrium blood-pool scintigraphy. [2015]

9. United States pubmed.ncbi.nlm.nih.gov

Responses of abdominal vascular capacitance to stimulation of splachnic nerves. [2017]

10. United States pubmed.ncbi.nlm.nih.gov

Endotoxemia alters splanchnic capacitance. [2019]

11. United States pubmed.ncbi.nlm.nih.gov

Global sensitivity analysis of hepatic venous pressure gradient (HVPG) measurement with a stochastic computational model of the hepatic circulation. [2019]

12. United States pubmed.ncbi.nlm.nih.gov

Splanchnic blood flow in patients with cirrhosis and portal hypertension: investigation with duplex Doppler US. [2016]