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| Name | Class |
|---|---|
| Rigshospitalet, Denmark | OTHER |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Saline | Active Comparator | Saline infusion, oral glucose (POTS and healthy) |
|
| GIP antagonist | Experimental | GIP(3-30)NH2 infusion, oral glucose (POTS and healthy) |
|
| GLP-1 antagonist | Experimental | Exendin(9-39)NH2 infusion, oral glucose (only in healthy) |
|
| CCK agonist | Experimental | CCK-8 infusion, oral glucose (POTS and healthy) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Saline/Placebo | Other | NaCl(9mg/ml) |
| |
| GIPR antagonist |
| Measure | Description | Time Frame |
|---|---|---|
| Redistribution of splanchnic blood flow in the vessel mesenteric superior artery (MR) | Blood flow in the superior mesenteric artery measured with MR ml/min | Continuously for 80 minutes/during infusions |
| Measure | Description | Time Frame |
|---|---|---|
| Blood flow in portal vein | Blood flow in the portal vein measured with MR-scans in ml/min | Continuously for 80 minutes/during infusions |
| Blood Flow in celiac trunk | Blood flow in the celiac trunk measured with MR-scans in ml/min |
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Inclusion Criteria POTS patients:
Exclusion Criteria:
Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Sophie W Nielsen, MD | Contact | + 45 27 26 79 94 | sophie.nielsen@sund.ku.dk | |
| Lærke S Gasbjerg, MD, PhD | Contact | +45 25 34 68 94 | lsg@sund.ku.dk |
| Name | Affiliation | Role |
|---|---|---|
| Lærke S Gasbjerg, MD, PhD | University of Copenhagen, Rigshospitalet | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Rigshospitalet | Recruiting | Copenhagen | 2100 | Denmark |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 18385466 | Background | Someya N, Endo MY, Fukuba Y, Hayashi N. Blood flow responses in celiac and superior mesenteric arteries in the initial phase of digestion. Am J Physiol Regul Integr Comp Physiol. 2008 Jun;294(6):R1790-6. doi: 10.1152/ajpregu.00553.2007. Epub 2008 Apr 2. | |
| 7614106 | Background | Parker DR, Carlisle K, Cowan FJ, Corrall RJ, Read AE. Postprandial mesenteric blood flow in humans: relationship to endogenous gastrointestinal hormone secretion and energy content of food. Eur J Gastroenterol Hepatol. 1995 May;7(5):435-40. |
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Will share upon request
Data will be shared upon request after study completion
Qualified researchers can request access by submitting a proposal to the study sponsor. Data will be shared via a secure online repository upon approval of the request.
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Apr 28, 2025 |
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Single blinded, randomized, crossover trial
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| Other |
GIP(3-30)NH2 |
|
| GLP-1R antagonist | Other | GLP-1(9-39)NH2 |
|
| CCK agonist | Other | CCK-8 |
|
| 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 | 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 | 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 | 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. | 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, | One measurement at baseline visit |
| Blood sample for glucose | Glucose measurements | 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 | One measurement at baseline visit |
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| 25980576 | Background | Sheldon RS, Grubb BP 2nd, Olshansky B, Shen WK, Calkins H, Brignole M, Raj SR, Krahn AD, Morillo CA, Stewart JM, Sutton R, Sandroni P, Friday KJ, Hachul DT, Cohen MI, Lau DH, Mayuga KA, Moak JP, Sandhu RK, Kanjwal K. 2015 heart rhythm society expert consensus statement on the diagnosis and treatment of postural tachycardia syndrome, inappropriate sinus tachycardia, and vasovagal syncope. Heart Rhythm. 2015 Jun;12(6):e41-63. doi: 10.1016/j.hrthm.2015.03.029. Epub 2015 May 14. No abstract available. |
| Apr 28, 2025 |
| Prot_SAP_000.pdf |
| ID | Term |
|---|---|
| D054972 | Postural Orthostatic Tachycardia Syndrome |
| ID | Term |
|---|---|
| D054971 | Orthostatic Intolerance |
| D054969 | Primary Dysautonomias |
| D001342 | Autonomic Nervous System Diseases |
| D009422 | Nervous System Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| D012965 | Sodium Chloride |
| ID | Term |
|---|---|
| D002712 | Chlorides |
| D006851 | Hydrochloric Acid |
| D017606 | Chlorine Compounds |
| D007287 | Inorganic Chemicals |
| D017670 | Sodium Compounds |
Not provided
Not provided