The Involvement of the Gut Hormone GIP in the Pathophysiology of Post Prandial Hypotension (GA-21)

The present study investigates the involvement of the gut hormone glucose-dependent insulinotropic polypeptide (GIP) in the pathophysiology of postprandial hypotension (PPH)

Study Overview

• Status: Recruiting
• Conditions: PostPrandial Hypotension
• Intervention / Treatment: Other: Intravenous infusion of GIPRA; Other: Intravenous infusion of saline

Detailed Description

The study is an exploratory, randomised, placebo-controlled, double-blind crossover study comprising two experimental days with an infusion of the GIP receptor antagonist, GIP(3-30)NH2 (NH2 is the aminogroup), and placebo (saline) during a 180-minute mixed meal test (MMT). Eighteen participants, men and women, with MMT confirmed PPH will be included in the study.

• Study Type: Interventional
• Enrollment (Estimated): 18
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Lise Wilki-Kurtzhals, MD; Phone Number: +4526204303; Email: lise.wilki-kurtzhals@regionh.dk

Study Locations

• Denmark
  • Hellerup
    • Copenhagen, Hellerup, Denmark, 2900
      • Recruiting
      • Center for Clinical Metabolic Research
      • Contact: Lise Wilki-Kurtzhals, MD; Phone Number: +4526204303; Email: lise.wilki-kurtzhals@regionh.dk
      • Sub-Investigator: Casper Nielsen, Postdoc
      • Sub-Investigator: Lærke Smidt, Postdoc
      • Sub-Investigator: Asger Lund, PhD
      • Sub-Investigator: Mikkel Christensen, Professor
      • Sub-Investigator: Filip Knop, Professor

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Age 18-85 years
2. History of PPH-related symptoms like dizziness, lightheadedness, palpitations, or fainting after meal ingestion
3. Informed consent

Exclusion Criteria:

1. Not fulfilling the PPH diagnosis during the mixed meal test or during the test meal with increased (+25%) number of calories
2. Treatment with antihypertensives
3. Treatment with SNRI (Serotonin and Noradrenalin Reuptake Inhibitor) or treatment within three months before screening visit
4. Allergy or intolerance to ingredients included in the mixed meal
5. Any ongoing medication that the investigator evaluates would interfere with trial participation
6. Any physical or psychological condition that the investigator evaluates would interfere with trial participation, including any acute or chronic illnesses
7. Anaemia (haemoglobin below normal range <7.3 mmol/L for women and <8.3 mmol/L for men)
8. Moderate to severe loss of kidney function (estimated glomerular filtration rate (eGFR) <45 ml/min/1.73 m2) at screening
9. Known liver disease (except for simple steatosis) and/or elevated plasma alanine aminotransferase (ALT) > three times the upper limit of normal at screening
10. Any concomitant disease or treatment that, at the discretion of the investigators, might jeopardize the participant's safety during the trial
11. Alcohol/drug abuse as per discretion of the investigators
12. Pregnancy or breastfeeding
13. Participation in any other clinical trial during study period
14. Mental incapacity or language barriers that preclude adequate understanding or cooperation or unwillingness to comply with trial requirements or pr discretion of the investigator

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Saline; Intravenous infusion of isotonic saline 9 mg/ml added 0,5% human serum albumin	Other: Intravenous infusion of saline; Intravenous infusion of isotonic saline 9 mg/ml added 0,5% human serum albumin during experimental days; Other Names: Placebo (Saline)
Experimental: GIPRA (Glucose-dependent Insulinotropic Polypepetide Receptor Antagonist); Intravenous infusion of GIP(3-30)NH2 in a concentration of 1,000 pmol/kg/min	Other: Intravenous infusion of GIPRA; Intravenous infusion of GIP(3-30)NH2 in a concentration of 1,000 pmol/kg/min during experimental days; Other Names: GIP(3-30)NH2

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Nadir systolic blood pressure (mmHg)	Nadir and time to nadir	0-180 minutes
Nadir systolic blood pressure (SBP) (mmHg)	Baseline	-45-0 minutes

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Occurrence of PPH	(Yes/No) PPH is defined as either a drop in SBP >20 mmHg from baseline or SBP <90 mmHg	0-180 minutes
Systolic blood pressure (mmHg)	Baseline	-45-0 minutes
Diastolic blood pressure (mmHg)	Baseline	-45-0 minutes
Diastolic blood pressure (mmHg)	Peak, nadir and iAUC	0-180 minutes
Heart rate (beats/min)	Baseline	-45-0 minutes
Heart rate (beats/min)	Peak, nadir and iAUC	0-180 minutes
Stroke volumen (ml)	Baseline	-45-0 minutes
Stroke volumen (ml)	Peak, nadir and iAUC	0-180 minutes
Cardiac output (l/min)	Baseline	-45-0 minutes
Cardiac output (l/min)	Peak, nadir and iAUC	0-180 minutes
Systolic blood pressure (mmHg)	Peak, nadir and iAUC (incremental area under the curve)	0-180 minutes

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma glucose	Baseline	-45-0 minutes
Plasma glucose	Peak, nadir and iAUC	0-180 minutes
Gastric emptying rate	Plasma acetaminophen, baseline	-45-0 minutes
Gastric emptying rate	Plasma acetaminophen, peak and time to peak	0-180 minutes
Plasma GIP(3-30)NH2	Baseline	-45-0 minutes
Plasma GIP(3-30)NH2	Peak and iAUC	0-180 minutes

Collaborators and Investigators

• Sponsor: University Hospital, Gentofte, Copenhagen
• Investigators: Principal Investigator: Lise Wilki-Kurtzhals, University Hospital, Gentofte, Copenhagen

Study record dates

Study Major Dates

• Study Start (Estimated): March 1, 2024
• Primary Completion (Estimated): March 31, 2025
• Study Completion (Estimated): March 31, 2025

Study Registration Dates

• First Submitted: January 5, 2024
• First Submitted That Met QC Criteria: January 5, 2024
• First Posted (Actual): January 17, 2024

Study Record Updates

• Last Update Posted (Estimated): February 9, 2024
• Last Update Submitted That Met QC Criteria: February 7, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Glucose-dependent insulinotropic polypeptide; GIP; GIP receptor antagonist; GIP(3-30)NH2; Postprandial hypotension
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hypotension
• Other Study ID Numbers: GIPR-Ant-21

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No