Splanchnic Venous Capacitance in Postural Tachycardia Syndrome

NCT05375968 | Recruiting Phase 2 DMC FDA Drug FDA Device

• 2 other identifiers: POTS-GIPR01HL15920301A1
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

Postural tachycardia syndrome (POTS) affects ≈3 million young people, characterized by chronic presyncopal symptoms characterized by dizziness, lightheadedness, and orthostatic tachycardia that occur while standing. Across-sectional survey found that 25% of these patients complains that meals rich in carbohydrates are among the factors that further exacerbate POTS's symptoms and cause a myriad of gastrointestinal symptoms. The splanchnic circulation is the largest blood volume reservoir of the human body, storing ≈25% of the total blood volume and contributing to sudden, and large, fluctuations in the stroke volume (SV). The orthostatic changes in systemic hemodynamics are particularly magnified after meals, due to increased blood volume sequestration triggered by the release of gastrointestinal peptides with vasodilatory properties. The purpose of this study is to determine if the worsening orthostatic tachycardia and symptoms after glucose ingestion in POTS patients are due to a greater increase in splanchnic venous capacitance and excessive blood pooling on standing as compare to Healthy controls. The study will also determine if glucose-induced GIP secretion increases splanchnic venous capacitance, orthostatic tachycardia and worsening POTS postprandial symptoms. For this purpose subjects will be further randomized to either saline versus GIP(3-30)NH2 acute infusion, to measure the changes their 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 hours.

Conditions

Postural Tachycardia Syndrome (POTS)

Keywords

Glucose-dependent Insulinotropic Polypeptide (GIP)

Outcome Measures

Primary Outcomes (3)

• Change in splanchnic venous capacitance in Postural Orthostatic Tachycardia Syndrome

  The changes in splanchnic venous capacitance and superior mesenteric arterial flow will be measured, before and after a 75 gram of oral glucose challenge. It will compared in POTS and Healthy controls. While segmental bio impedance is monitored, continuous positive airway pressure (CPAP) will be applied sequentially at 0, 4, 8, 12 and 16 cm H2O for about 30 seconds each; this positive airway pressure will increase the intrathoracic pressure, which is transmitted to the venous circulation. Pressure (CPAP pressure, x-axis) - volume (splanchnic vascular volume measured by segmental impedance and expressed as % change from baseline, y-axis) relationships are then constructed to assess for splanchnic venous capacitance.

  Baseline up to 180 minutes post glucose challenge

• Effect of glucose-induced GIP secretion on splanchnic venous capacitance

  25 participants with POTS diagnosis, will be randomized them to either saline versus GIP antagonist (GIP(3-30)NH2) acute infusion. We will measure changes in their 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

  0-180 mins

• Effect of glucose-induced GIP secretion on POTS postprandial symptoms.

  Compare the post prandial symptoms on the participants who got infused with GIP antagonist GIP(3-30)NH2 and compare it with Saline infused participants at baseline and 45 degree head tilt. Total of 25 participants with diagnosis of POTS will randomized at visit 2, as 1:1 saline vs GIP antagonist GIP(3-30)NH2 At visit 3, the subjects who received Saline, will get GIP antagonist GIP(3-30)NH2 , vice versa.

  0-90 mins

Secondary Outcomes (1)

• Measure Glucose-dependent Insulinotropic polypeptide (GIP) hormone level in POTS patients and Controls after 75 grams of glucose ingestion

  Baseline up to 180 minutes post glucose challenge

Study Arms (2)

Changes in Splanchnic venous capacitance(SVC) before and after a 75-g oral glucose challenge

ACTIVE COMPARATOR

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

Diagnostic Test: Measurement of Splanchnic venous capacitance(SVC)done at Baseline and after 90 min of 75 g glucose in Healthy Controls POTS patients; Diagnostic Test: Measurement of Splanchnic venous capacitance(SVC)done at Baseline and after 90 min of 75 g glucose in Healthy Controls

Effect of GIP antagonist GIP(3-30)NH2 Vs Saline on splanchnic venous capacitance on POTS patients

PLACEBO COMPARATOR

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.

Drug: Compare change is SVC and SMA flow due to GIP antagonist GIP(3-30)NH2; Drug: Compare change is SVC and SMA flow due to saline

Interventions

Compare change is SVC and SMA flow due to GIP antagonist GIP(3-30)NH2 DRUG

Participants with POTS will be randomize to either saline versus GIP(3-30)NH2 acute infusion. We will measure changes in their 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. Notably, we will assess changes in venous capacitance using segmental impedance to measure the effect of graded positive airway pressure (CPAP) on splanchnic blood volume.

Effect of GIP antagonist GIP(3-30)NH2 Vs Saline on splanchnic venous capacitance on POTS patients

Compare change is SVC and SMA flow due to saline DRUG

Participants with POTS will be randomize to either saline versus GIP(3-30)NH2 acute infusion. We will measure changes in their 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. Notably, we will assess changes in venous capacitance using segmental impedance to measure the effect of graded positive airway pressure (CPAP) on splanchnic blood volume.

Effect of GIP antagonist GIP(3-30)NH2 Vs Saline on splanchnic venous capacitance on POTS patients

Measurement of Splanchnic venous capacitance(SVC)done at Baseline and after 90 min of 75 g glucose in Healthy Controls DIAGNOSTIC_TEST

While segmental bioimpedance is monitored, continuous positive airway pressure (CPAP) will be applied sequentially at 0, 4, 8, 12, and 16 cm H2O for about 30 seconds each. This positive airway pressure will increase the intrathoracic pressure, which is transmitted to the venous circulation. Pressure (CPAP pressure, X axis) - volume (splanchnic vascular volume measured by segmental impedance and expressed as % change from baseline, Y axis) relationships are then constructed to assess for splanchnic venous capacitance

Changes in Splanchnic venous capacitance(SVC) before and after a 75-g oral glucose challenge

Measurement of Splanchnic venous capacitance(SVC)done at Baseline and after 90 min of 75 g glucose in Healthy Controls POTS patients DIAGNOSTIC_TEST

While segmental bioimpedance is monitored, continuous positive airway pressure (CPAP) will be applied sequentially at 0, 4, 8, 12, and 16 cm H2O for about 30 seconds each. This positive airway pressure will increase the intrathoracic pressure, which is transmitted to the venous circulation. Pressure (CPAP pressure, X axis) - volume (splanchnic vascular volume measured by segmental impedance and expressed as % change from baseline, Y axis) relationships are then constructed to assess for splanchnic venous capacitance

Changes in Splanchnic venous capacitance(SVC) before and after a 75-g oral glucose challenge

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Between 18 and 50years of age
• Cases: Diagnosis of POTS with presyncope symptoms after meals Or
• Controls:
• With no significant past medical history, non-smokers and not on chronic medications.
• Body mass index (BMI) between 18.5 to 29.9 kg/m2
• If pre-menopausal women: must have regular menstrual cycle.

You may not qualify if:

• BMI above ≥30 kg/m2
• Irregular menstrual cycle
• Intolerance to CPAP.
• Chronic use of acetaminophen
• Heart problems: myocardial infarction, angina, heart failure, stroke
• Undergone any heart related procedures or stents or on pacemaker.
• Uncontrolled hypertension.
• Type 1 or type 2 diabetes mellitus
• Pregnant or breast-feeding women.
• Impaired liver function
• Impaired Kidney function test.
• Anemia (Hematocrit\<34%).
• Ongoing substance abuse.
• Subjects with abnormal EKG
• History of seizures.

Sponsors & Collaborators

• Vanderbilt University Medical Center: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (1)

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

RECRUITING

Related Publications (5)

• Jacob G, Costa F, Shannon JR, Robertson RM, Wathen M, Stein M, Biaggioni I, Ertl A, Black B, Robertson D. The neuropathic postural tachycardia syndrome. N Engl J Med. 2000 Oct 5;343(14):1008-14. doi: 10.1056/NEJM200010053431404.

  PMID: 11018167 RESULT

• Shibao C, Arzubiaga C, Roberts LJ 2nd, Raj S, Black B, Harris P, Biaggioni I. Hyperadrenergic postural tachycardia syndrome in mast cell activation disorders. Hypertension. 2005 Mar;45(3):385-90. doi: 10.1161/01.HYP.0000158259.68614.40. Epub 2005 Feb 14.

  PMID: 15710782 RESULT

• Prentky RA, Watt NF, Fryer JH. Longitudinal social competence and adult psychiatric symptoms at first hospitalization. Schizophr Bull. 1979;5(2):306-12. doi: 10.1093/schbul/5.2.306.

  PMID: 462143 RESULT

• Bourne KM, Stiles LE, Raj SR, Shibao CA. Do meals affect heart rate and symptoms in postural orthostatic tachycardia syndrome? Clin Auton Res. 2022 Feb;32(1):65-67. doi: 10.1007/s10286-021-00835-0. Epub 2021 Nov 18. No abstract available.

  PMID: 34792683 RESULT

• Breier NC, Paranjape SY, Scudder S, Mehr SE, Diedrich A, Flynn CR, Okamoto LE, Hartmann B, Gasbjerg LS, Shibao CA. Worsening Postural Tachycardia Syndrome Is Associated With Increased Glucose-Dependent Insulinotropic Polypeptide Secretion. Hypertension. 2022 May;79(5):e89-e99. doi: 10.1161/HYPERTENSIONAHA.121.17852. Epub 2022 Mar 2.

  PMID: 35232225 RESULT

MeSH Terms

Conditions

Postural Orthostatic Tachycardia Syndrome

Condition Hierarchy (Ancestors)

Orthostatic Intolerance; Primary Dysautonomias; Autonomic Nervous System Diseases; Nervous System Diseases

Study Officials

• Cyndya Shibao, M.D

  Vanderbilt University Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Pedro J Ortiz, MD

CONTACT

689-233-2623; pedro.ortiz.saavedra@vumc.org

Meena Golchha, MD

CONTACT

615-322-3447; meenakshi.golchha@vumc.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Masking Details: The randomization schedule will be generated by a statistician who is not related to the study. The blinded study intervention will be infused, which medication one receives will be decided by chance, like the toss of a coin .The subjects who received saline at visit 2, will get the study drug GIP(3-30)NH2 at visit 3, and vice versa
• Purpose: DIAGNOSTIC
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: April 19, 2022
• First Posted: May 17, 2022
• Study Start: February 25, 2023
• Primary Completion (Estimated): May 31, 2027
• Study Completion (Estimated): June 1, 2028
• Last Updated: December 5, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)