Obesity
Conditions
Brief summary
This research project aims to investigate the role of endogenous GIP during fasting. With the infusion of a GIP receptor antagonist (GIP\[3-30\]NH2), is it possible to selectively remove the effect of endogenous GIP, and thus describe its effects by comparing it with what happens during a saline infusion.
Detailed description
This research project investigates the effects endogenous GIP has in the body of healthy, overweight people. Two trial days will be held. The participant will receive intravenous infusion of either GIP\[3-30\]NH2 (800 pmol/kg/min) or placebo (saline) in a randomized order. After 20 minutes, GIP\[3-30\]NH2 is expected to have maximum effect. On time of 180 minutes, an ad libitum meal is served, which is consumed during continued infusion. When the participant is comfortably full, the infusion is turned off and the trial day ends. During the day, the participant assesses and notes on standardized VAS schedules current appetite, satiety, nausea, fatigue, malaise and thirst. Blood pressure and heart rate are measured every 30 minutes throughout the trial day and blood samples are taken. In total, there will be drawn ten blood samples between intervals of 15 to 30 min. Three times along the way, the activity in the brown adipose tissue is measured with a thermal camera (temperature measurements over the skin on the chest) and the resting metabolic rate is determined with indirect calorimetry (inhaled and exhaled air is captured by breathing under a large plastic bell).
Interventions
BIOLOGICALGIP[3-30]NH2
GIP\[3-30\]NH2 is the naturally occurring shorter (truncated) variant of GIP\[1-42\]. GIP\[3-30\]NH2 also stimulates the GIP receptor and therefore acts like a GIP receptorantagonist
OTHERSaline
Sodium chlorid with 0,5% human serum albumin.
Sponsors
Frederikke Koefoed-Hansen
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Masking description
The infusion is mixed by an external coordinator. Neither the investigator or the participants knows whether is the GIP\[3-30\]NH2 infusion or saline infusion that is being given. Which infusion that is given on each trial day is randomized for each participant.
Intervention model description
The trial is a randomized, double-blind, crossover study. We give intravenous infusion of GIP\[3-30\]NH2, and thus describe the effects of GIP by comparing with what happens during a saline infusion (placebo).
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
Yes
Inclusion criteria
* 18-70 years * BMI \> 30 kg/m2 * Body fat percentage \> 25 % for men og \> 35 % for women
Exclusion criteria
* Type 1 diabetes and/or type 2 diabetes diagnosis * Other chronic condition * Treatment with medications or supplements that cannot be paused for 12 hours * \> 14 units of alcohol weekly or drug abuse * Circulating liver enzymes (alanine aminotransferase (ALAT) and/or aspartate aminotransferase (ASAT)) ≥ 2 × normal value * Renal impairment (eGFR \< 90 or creatinine level above the reference range) * Uncontrolled high resting blood pressure (above 140/90 mmHg) * Low blood percentage (hemoglobin \< reference range (different for women and men)) * Special diet or planned weight change within the trial period * Any disease/condition that investigators believe will interfere with study participation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Plasma glucagon concentrations | Four hours | Measured in mmol/L. The primary endpoint is plasma glucagon concentrations during GIP\[3-30\]NH2 infusion compared to placebo.Area under the curve (AUC) for plasma glucagon (AUCglucagon) is quantified both as absolute and in baseline-subtracted values (bsAUCglucagon) and the effect of the GIP receptor antagonist will be calculated as a percentage reduction of bsAUC glucagon relative to bsAUC glucagon during the placebo infusion. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Plasma levels of insulin | Four hours | Measured in mmol/L |
| Resting metabolic rate | 15 minutes | Measured in resting energy expenditure (REE) and respiratory quotient (RQ) |
| Activity in brown adipose tissue | 10 minutes | Measured by thermal camera |
| Plasma levels of C-peptide | Four hours | Measured in mmol/L |
| Blood pressure | Pre-intervention at time -30 and -20 min. During infusion at time 0 min, 30 min, 60 min, 90 min, 120 min, 160 min and 180 min. | mmHg |
| Puls | Pre-intervention at time -30 and -20 minutes. During infusion at time 0 minutes, 30 minutes, 60 minutes, 90 minutes, 120 minutes, 160 minutes, and 180 minutes | Beats pr. minutes |
| Appetite | 30 minutes | Measured in kilogram food intake |
Countries
Denmark
Outcome results
None listed