Healthy, Postural Orthostatic Tachycardia Syndrome (POTS)
Conditions
Keywords
Postural Orthostatic Tachycardia Syndrome, POTS, Glucose-dependent insulinotropic polypeptide, GIP, Glucagon-like peptide-1, Glucagon-like peptide-2, GLP-1, GLP-2, CCK-8, Cholecystokinin, Splanchnic Blood Flow
Brief summary
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.
Detailed description
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.
Interventions
OTHERSaline/Placebo
NaCl(9mg/ml)
OTHERGIPR antagonist
GIP(3-30)NH2
OTHERGLP-1R antagonist
GLP-1(9-39)NH2
OTHERCCK agonist
CCK-8
Sponsors
Rigshospitalet, Denmark
University of Copenhagen
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
SINGLE (Subject)
Intervention model description
Single blinded, randomized, crossover trial
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
Yes
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
* 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: * Age 18-50 * Waist ratio \<180 cm * Matched a POTS patient in age, sex and BMI
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Redistribution of splanchnic blood flow in the vessel mesenteric superior artery (MR) | Continuously for 80 minutes/during infusions | Blood flow in the superior mesenteric artery measured with MR ml/min |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Blood Flow in celiac trunk | Continuously for 80 minutes/during infusions | Blood flow in the celiac trunk measured with MR-scans in ml/min |
| Blood Flow in the hepatic artery | Continuously for 80 minutes/during infusions | Blood flow in the hepatic artery measured with MR-scans in ml/min |
| Blood samples for hormones | Every 10-20 minutes before and during and after the infusions and MR scans (120 minutes) | 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 |
| Gastric emptying/Blood sample of paracetamol | Every 10-20 minutes before, during and after the infusions and MRI scans (120 minutes) | Uptake/amount of paracetamol in the blood over time as a measure of gastric emptying |
| Blood flow in portal vein | Continuously for 80 minutes/during infusions | Blood flow in the portal vein measured with MR-scans in ml/min |
| Blood samples for genes | One measurement at baseline visit | Genes analyzed from buffycoat: GLP-1R: NM\_002062, GLP-2R: NM\_004246, GIPR: NM\_000164 and NM\_001308418, CCKR: NM\_000730 and NM\_176875, |
| Blood sample for glucose | Every 10-20 minutes before and during and after the infusions and MR scans (120 minutes) | Glucose measurements |
| Blood samples for autoantibodies | One measurement at baseline visit | 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 |
| Symptomscoring | Continously before and during the infusions (120 minutes) | 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. |
Countries
Denmark
Contacts
Primary ContactSophie W Nielsen, MD
Backup ContactLærke S Gasbjerg, MD, PhD
Outcome results
None listed