SVC Assessment for POTS

Overseen By Pedro J Ortiz, MD

Age: 18 - 65

Sex: Any

Trial Phase: Phase 2

Sponsor: Vanderbilt University Medical Center

Must not be taking: Acetaminophen, Statins, Corticosteroids, others

Disqualifiers: Heart problems, Diabetes, Pregnancy, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 4

Duration: 3 hours

50 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to understand why individuals with postural tachycardia syndrome (POTS) feel worse after consuming high-carbohydrate foods. Researchers seek to determine if increased blood pooling in the stomach area post-meal is linked to these symptoms. Participants will receive glucose (a type of sugar) to observe its effects on blood flow and heart rate while lying down and standing up. The trial seeks individuals diagnosed with POTS who experience dizziness or lightheadedness after meals. The study will measure splanchnic venous capacitance (SVC) to assess changes in blood flow. As a Phase 2 trial, this research focuses on evaluating the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to significant findings.

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 prior data suggests that this measurement of splanchnic venous capacitance is safe?

Research has shown that the treatment GIP(3-30)NH2 works better at certain doses. In earlier studies, participants generally tolerated GIP(3-30)NH2 well, with no major reports of serious side effects. This suggests the treatment is usually safe for people. However, participants should discuss possible risks with their doctors before joining a trial. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it aims to uncover how the body's blood vessels respond to changes in blood flow and pressure, specifically in people with Postural Tachycardia Syndrome (POTS). Unlike standard treatments that focus on managing symptoms like rapid heart rate, this study is investigating the role of splanchnic venous capacitance (SVC) and glucose-dependent insulinotropic polypeptide (GIP) hormones. The trial could pave the way for new therapies targeting the blood flow dynamics in POTS, offering a fresh perspective on managing this challenging condition. By exploring these unique physiological mechanisms, the trial could lead to breakthroughs in understanding and treating POTS beyond current symptomatic relief options.

What evidence suggests that this trial's treatments could be effective for POTS?

In this trial, one arm will assess the effect of the treatment GIP(3-30)NH2 on people with POTS by blocking a gut hormone that can worsen symptoms. Research has shown that GIP(3-30)NH2 may reduce the effects of this hormone, potentially preventing blood from pooling and improving blood flow after eating. This treatment targets blood volume in the stomach area and may help maintain steady blood pressure and heart rate when standing. Early results suggest that GIP(3-30)NH2 could reduce the dizziness and lightheadedness often experienced in POTS after meals. ^{1 2 3 4 5}

Who Is on the Research Team?

Cyndya A Shibao, MD

Principal Investigator

Vanderbilt University Medical Center

Are You a Good Fit for This Trial?

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 a pre-menopausal woman with a regular menstrual cycle.

I have been diagnosed with POTS and feel faint after eating.

I have POTS and feel faint after eating or I'm healthy, don't smoke, and take no regular meds.

Exclusion Criteria

I have rheumatoid arthritis.

I regularly use acetaminophen.

I am taking statins for high cholesterol.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Measurement of Splanchnic venous capacitance(SVC)

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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 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]

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 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]

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]

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 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]

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]

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]

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]

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]

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Worsening Postural Tachycardia Syndrome Is Associated ...

Dose-dependent efficacy of the glucose-dependent insulinotropic polypeptide (GIP) receptor antagonist GIP(3-30)NH2 on GIP actions in humans.