Interplay Between Gut Hormones and Autonomic Postprandial Blood Flow Regulation in Patients With POTS
Phase: NA
Conditions: Postural Orthostatic Tachycardia Syndrome (POTS), Healthy
Sponsor: University of Copenhagen

 
 
28.04.25 
 
 
Interplay between gut hormones and autonomic 
postprandial blood flow regulation in patients with 
POTS 
 
Department of Biomedical Sciences, 
University of Copenhagen 
 
Rigshospitalet,  
Department for clinical physiology and nuclear medicine, 
Denmark 
 
H-24030176 
Date: 28/04/25 
 
 

 
 
28.04.25 
Title: Interplay between gut hormones and autonomic postprandial blood flow regulation in 
patients with POTS 
 
Approved ethical committee ID: H-24030176 
 
Project Group: 
Sophie Woge Nielsen, MD, PhD-student 
Rasmus Syberg Rasmussen, cand.scient., PhD-student 
Mark Bitsch Vestergaard, cand. polyt., PhD., post.doc 
Louise Schouborg Brinth, MD, PhD 
Bolette Hartmann, cand.scient., PhD, associate professor 
Professor Mette Marie Rosenkilde, MD, PhD 
Professor Jens Frederik Rehfeld, MD, DMSc.,  
Professor Jens Juul Holst, MD, DMSc. 
Ulrik Bjørn Andersen, MD, 
Bryan Haddock, cand.scient., PhD,  
Lærke Smidt Gasbjerg, MD, PhD 
 
Background:  
In order to take up nutrients the blood flow to the gastrointestinal tract increase after a meal and these 
regulations are partially controlled by gastrointestinal hormones. Postural Orthostatic Tachycardia 
Syndrome (POTS) is a disease with autonomous dysfunction in the nervous system that leads to 
symptoms when standing and after meal due to poor control of the blood flow distribution. The 
gastrointestinal hormone glucose-dependent insulinotropic polypeptide (GIP) is increased in patients 
with POTS and has vasodilating effects in the larger abdominal vessels. In this study we investigate 
if GIP and other gastrointestinal hormones are involved in control of postprandial blood flow to the 
intestines in healthy and patients, and if they are thereby implicated in the pathophysiology of POTS.  
 
Aim: We aim to investigate the interplay between the gastrointestinal hormones GIP, GLP-1and CCK 
and their regulation in gastrointestinal blood flow regulation in the larger abdominal vessels: superior 
mesenteric artery, celiac trunk, portal vein and hepatic artery. We will investigate this by infusion of 
the hormones or hormonal antagonists on different days, while performing MR-scans of the abdomen 
during an Oral Glucose Tolerance Test (OGTT) in POTS patients and sex-, age- and BMI-matched 
healthy participants. 
 
Hypothesis: The expectation in this study is that OGTT intake will increase the blood flow to the 
intestines and thereby increase the flow in the superior mesenteric artery and celiac trunk while it will 
also alter the blood flow in the portal vein and hepatic artery. The blood flow after OGTT is however 
expected to decrease after infusion of hormone antagonist for GIP and GLP-1 but to increase after 
infusion of CCK, that will empty the gallbladder. In POTS patients it is expected that the increase in 
blood flow after OGTT will be more pronounced than that in healthy and that the hormone agonists 
and antagonists will lead to larger fluctuations in the abdominal blood flow in POTS patients.  
 
Design: 
Randomized, placebo controlled, crossover, single blind design in 15 patients with POTS and 15 
healthy matched participants.  
 
 

 
 
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Baseline information: 
A description of the baseline measured will be presented in a table, including the following measures: 
Age, Weight, Height, BMI, Hemoglobin, Leucocytes, Vitamin D, Fasting glucose, HbA1c, Sex, and 
Blood pressure. The data will be presented in Median and range. 
 
Statistical analysis and graphs: 
The flow data is analyzed in R studio by a linear mixed model, that pairs the data, and compared the 
interventions after steady state of the infusion of hormone antagonists, agonist or placebo. The 
primary statistical analysis will be done between the interventions: The infusion of GIP(3-30)NH2 
and saline after OGTT intake and the difference in blood flow in the superior mesenteric artery 
between healthy and patients with POTS. Furthermore, the data will be presented in GraphPad Prism 
10. A data table will present the flow measurements of each intervention, including mean and 95% 
confidence intervals 
 
Criteria: 
Inclusion criteria POTS patients: 
  - Previously diagnosed with POTS in tilt test or active stand-test (either newly diagnosed within last 
3 months or in new tilt test/active stand test during screenings visit) 
- Reproducible orthostatic intolerance with raise in HR on >30 bpm when standing within 10 minutes 
of change of supine to standing in age >19 years or >40 bpm in age 18-19 years. 
- POTS symptoms/orthostatic intolerance 
- Age 18-50 
- Waist ratio <180 cm 
 
Exclusion criteria POTS patients: 
- Chronic illness  
- Metallic implants 
- Above 10 alcoholic drinks or week or substance abuse 
- Other types of sinus tachycardia or heart disease 
- Liverenzymes two times above normal values 
- Decreased kidney function eGFR <90 or elevated kreatinkinasis 
- Thyroid disease or TSH out of reference 
- Uncontrollable low or high blood pressure 
- Blood vessels that cannot be visualized on MR  
- Any disease that might influence the health of the participant during the study or participants that 
receives medicine that cannot be paused for 36 hours 
 
Inclusion criteria healthy participants: 
 - Age 18-50 
- Waist ratio <180 cm 
- Matched a POTS patient in age, sex and BMI 
 
Exclusion criteria healthy participants: 
- Chronic illness  
- Metallic implants 
- Above 10 alcoholic drinks or week or substance abuse 
- POTS; other types of sinus tachycardia or heart disease 
- Liverenzymes two times above normal values 

 
 
28.04.25 
- Decreased kidney function eGFR <90 or elevated kreatinkinasis 
- Thyroid disease or TSH out of reference 
- Uncontrollable low or high blood pressure, Orthostatic hypotension 
- Blood vessels that cannot be visualized on MR  
- Any disease that might influence the health of the participant during the study or participants that 
receives medicine that cannot be paused for 36 hours 
 
Methods and outcomes: Phase-contrast magnetic resonance imaging (PC-MRI) is used to calculate 
blood flow in the blood vessels: superior mesenteric artery, portal vein, celiac trunk and hepatic artery 
during the infusion of either saline, GIP(3-30)NH2, Exendin(9-39) NH2, receptor antagonist or CCK-
8 receptor agonist. Patients with POTS will participate in three study days with infusion of either: 
GIP(3-30)NH2, CCK-8 or saline. Healthy participants will participate in four days with infusion of 
either: GIP(3-30)NH2, Exendin(9-39) NH2, CCK-8 or saline.  
The main outcome of the study is blood flow in superior mesenteric artery between healthy and 
patients with POTS. On each study day, 11 MRI scans are performed (-60 min to 60 min after start 
of infusion) and 6 blood samples are taken. Blood glucose is measured bedside on whole blood. The 
blood samples collected are kept for analysis of: GLP-1(7-36 NH2, GLP-2(1-33), GIP(1-42), 
Exendin(9-39)NH2, GLP-2(3-33), GIP(3-30)NH2, Glukagon Insulin, C-peptid, Paracetamol, CCK.  
 
Autoantibodies for: Angiotensin-II-receptor-1 AT1R-ab , Endothelin-receptor-A ETAR-ab, Alpha1 
adrenergic-receptor-ab, Alpha2 adrenergic-receptor-ab, Beta1 adrenergic-receptor-ab, Beta2 
adrenergic-receptor-ab, Muscarinic cholinergic M1-receptor-ab, Muscarinic cholinergic M2-
receptor-ab, Muscarinic cholinergic M3-receptor-ab, Muscarinic cholinergic M4-receptor-ab and 
Muscarinic cholinergic M5-receptor-ab. 
 
Gene mutations in the genes coding for the hormone receptors: GLP-1R: NM_002062, GLP-2R: 
NM_004246, GIPR: NM_000164 and NM_001308418, CCKR: NM_000730 and NM_176875. 
 
Adverse event: 
All adverse events (AEs) or serious adverse event (SAE) are reported throughout the whole study 
period, any adverse event reported will be informed to the ethical committee responsible for the 
study. All AEs including local and systemic reactions not meeting the criteria for SAEs will be 
captured on the appropriate case report form. Information to be collected includes event description, 
time of onset, qualified medical professional’s assessment of severity, relationship to study product 
(assessed only by those with the training and authority to make a diagnosis), and time of 
resolution/stabilization of the event. All AEs occurring while on study must be documented 
appropriately regardless of relationship. All AEs will be followed to adequate resolution. 
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