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Splanchnic Venous Capacitance in Postural Tachycardia Syndrome

ConditionPostural Tachycardia Syndrome (POTS)
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18-50
SponsorVanderbilt University Medical Center

About this trial

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.

Eligibility criteria

This trial accepts healthy volunteers

Qualifiers

Between 18 and 50years of age

Cases: Diagnosis of POTS with presyncope symptoms after meals Or

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

Disqualifiers

BMI above ≥30 kg/m2

Irregular menstrual cycle

Intolerance to CPAP.

Chronic use of acetaminophen

Trial design

Design model

Crossover

Treatments tested in this trial

  • 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

  • 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

  • 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.

  • 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.

Treatment groups

50 Participants
are divided into 2 treatment groups
Group A: Changes in Splanchnic venous capacitance(SVC) before and after a 75-g oral glucose challengeActive comparator 2 interventions
Group B: Effect of GIP antagonist GIP(3-30)NH2 Vs Saline on splanchnic venous capacitance on POTS patientsPlacebo comparator 2 interventions

Trial outcomes

Primary outcomes

1

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.

Time frame
Baseline up to 180 minutes post glucose challenge
2

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

Time frame
0-180 mins
3

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.

Time frame
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

Measure and compare various GIP hormones (GLP-1, GLP-2, GIP, Vasoactive Intestinal Peptide(VIP)and glucagon) after ingesting 75-gram glucose for up to 180 minutes in POTS patients and healthy controls of similar age and BMI. Sequential blood draw will done to measure GIP hormones

Time frame
Baseline up to 180 minutes post glucose challenge

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Vanderbilt University Medical Center

Lead sponsor

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Source ClinicalTrials.gov
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