Mechanism of Glucose-dependent Insulinotropic Polypeptide (GIP) on Splanchnic Venous Capacitance in Postural Tachycardia Syndrome

Status: Recruiting
Location: See location...
Intervention Type: Drug, Diagnostic test
Study Type: Interventional
Study Phase: Phase 2
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.

Eligibility
Participation Requirements
Sex: All
Minimum Age: 18
Maximum Age: 50
Healthy Volunteers: t
View:

• 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.

Locations
United States
Tennessee
Vanderbilt University Medical Center
RECRUITING
Nashville
Contact Information
Primary
Pedro J Ortiz, MD
pedro.ortiz.saavedra@vumc.org
689-233-2623
Backup
Meena Golchha, MD
meenakshi.golchha@vumc.org
615-322-3447
Time Frame
Start Date: 2023-02-25
Estimated Completion Date: 2027-06-01
Participants
Target number of participants: 50
Treatments
Active_comparator: Changes in Splanchnic venous capacitance(SVC) before and after a 75-g oral glucose challenge
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
Placebo_comparator: Effect of GIP antagonist GIP(3-30)NH2 Vs Saline on splanchnic venous capacitance on POTS patients
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.
Sponsors
Leads: Vanderbilt University Medical Center
Collaborators: National Heart, Lung, and Blood Institute (NHLBI)

This content was sourced from clinicaltrials.gov