This study will describe the interplay between the gut hormones GIP and CCK and their regulation of blood flow to the large vessels in patients with Postural Orthostatic Tachycardia Syndrome (POTS) and GIP, CCK and GLP-1 in healthy. This is addressed by hormone infusions during MR-scans of the abdomen and intake of oral glucose.
Each participant will attend independent randomized experimental days with MR-scans during and intravenous infusions of hormones or placebo and ingestion of glucose or water. A continuous intravenous infusion of either GIP(3-30)NH2, CCK8- or saline for POTS-group or GIP(3-30)NH2, CCK-8, saline or exendin(9-39)NH2 in healthy is started while the participant lie in the scanner while scans, blood samples and questionnaires are repeated over the time course of 2 hours. At a specific timepoint the participants will ingest 75 g of glucose dissolved in 250 ml water.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
SINGLE
Enrollment
30
Rigshospitalet
Copenhagen, Denmark
RECRUITINGRedistribution of splanchnic blood flow in the vessel mesenteric superior artery (MR)
Blood flow in the superior mesenteric artery measured with MR ml/min
Time frame: Continuously for 80 minutes/during infusions
Blood flow in portal vein
Blood flow in the portal vein measured with MR-scans in ml/min
Time frame: Continuously for 80 minutes/during infusions
Blood Flow in celiac trunk
Blood flow in the celiac trunk measured with MR-scans in ml/min
Time frame: Continuously for 80 minutes/during infusions
Blood Flow in the hepatic artery
Blood flow in the hepatic artery measured with MR-scans in ml/min
Time frame: Continuously for 80 minutes/during infusions
Blood samples for hormones
Blood samples of hormones types: GLP-1(7-36 NH2), GLP-2(1-33), GIP(1-42), Exendin(9-39)NH2, GLP-2(3-33), GIP(3-30)NH2, Glucagon, Insulin/C-peptid, CCK
Time frame: Every 10-20 minutes before and during and after the infusions and MR scans (120 minutes)
Gastric emptying/Blood sample of paracetamol
Uptake/amount of paracetamol in the blood over time as a measure of gastric emptying
Time frame: Every 10-20 minutes before, during and after the infusions and MRI scans (120 minutes)
Symptomscoring
Symptomscoring of autonome dysfunction with VOSS (Vanderbilt Orthostatic Symptom Score) questionnaire: this consists of 10 symptoms: lightheadedness, brain fog, shortness of breath, palpitations, tremor, headache, tightness in chest, blurred vision, nausea and sleepiness rated from 0-10 where 0 is not ocurring and 10 is worts experienced.
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CCK-8
Time frame: Continously before and during the infusions (120 minutes)
Blood samples for genes
Genes analyzed from buffycoat: GLP-1R: NM\_002062, GLP-2R: NM\_004246, GIPR: NM\_000164 and NM\_001308418, CCKR: NM\_000730 and NM\_176875,
Time frame: One measurement at baseline visit
Blood sample for glucose
Glucose measurements
Time frame: Every 10-20 minutes before and during and after the infusions and MR scans (120 minutes)
Blood samples for autoantibodies
Autoantibodies: 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, Muscarinic cholinergic M5-receptor-ab
Time frame: One measurement at baseline visit