Healthy Overweight/Obese
Conditions
Keywords
Appetite, Glucose metabolism, Butyrate, Tributyrin
Brief summary
The goal of this double-blinded randomized clinical cross-over trial is to investigate the metabolic and appetite regulating effects of oral tributyrin (a butyrate pro-drug) administration vs placebo. The main questions it aims to answer are: * Does tributyrin have glucose lowering properties in humans? * Does tributyrin reduce appetite in humans? A sample size calculation estimated a minimum of 10 participants. We expect to include 12 participants in this study. Tributyrin or placebo is ingested once or twice daily for 2x2 weeks, separated by a washout period of minimum 2 weeks. On trial day following each 2-week period we assess: * Postprandial blood sugar levels * Hunger sensations (questionnaire) * Enteroendocrine hormone secretion (GLP-1, GIP, PYY, LEAP2, ghrelin) * Cardiac function (echocardiography) - An exploratory study evaluating the hemodynamic effects assessed by echocardiography is anticipated to be published separately. * Caloric intake (ad libitum meal test) * Gastric emptying rate (acetaminophen test) * Resting metabolic rate (indirect calorimetry). While at home, subjects will wear a sleep monitoring device for three consecutive nights and deliver fecal samples for analysis of short-chain fatty acid content and microbiota composition.
Interventions
DIETARY_SUPPLEMENTtributyrin
Oral ingestion of tributyrin (liquid) once daily (20 g x 1) for 7 days, then twice daily (20 g x 2) for 7 days.
DIETARY_SUPPLEMENTControl
Oral ingestion of water (liquid) with added bitter substance once daily (20 ml x 1) for 7 days, then twice daily (20 ml x 2) for 7 days
Sponsors
University of Aarhus
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* A body mass index (BMI) between 30-45 kg/m2 * Older than 18 years of age * HbA1c \< 48 mmol/mol * Hemoglobin within normal range (females: 7.3-9.5 mmol/L, males: 8.3-10.5 mmol/L) * Written and oral consent to participate
Exclusion criteria
* Medications affecting glucose metabolism and/or appetite (e.g. insulin, metformin, GLP-1 analogues) * Special diet (HCLF, ketogenic diets, vegan/vegetarian) * Ongoing cancer or other acute/chronic serious diseases (determined by PI) * Inability to understand Danish or English * Abnormal blood samples at screening visit (determined by PI and co-investigators) * Deemed unsuitable to participate by the PI and co-investigators
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Postprandial glucose | During trial day, time 120-300 minutes | iAUC of plasma glucose after ingestion of mixed meal |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Lipopolysaccharide Binding Protein (LPB) | On trial day, time 0 minutes | Plasma concentrations of LPB |
| Cortisol | On trial day, time 0 minutes | Plasma concentration of cortisol |
| Triglyceride | During trial day, time 0-300 minutes | Plasma concentrations of triglyceride |
| FFA | During trial day, time 0-300 minutes | Plasma concentrations of free fatty acids |
| Energy expenditure | After 60 and 150 minutes approximately | Indirect calorimetry |
| Sleep | Three nights at the end of the 2 week period at home | Assessment of sleep duration and stages |
| Fecal butyrate | Day 0, 7, 14 during the 2 week period | Fecal concentrations of butyrate |
| β-hydroxybutyrate | During trial day, time 0-300 minutes | Plasma concentrations of β-hydroxybutyrate |
| Lactate | During trial day, time 0-300 minutes | Plasma concentrations of lactate |
| C-reactive protein (CRP) | On trial day, time 0 minutes | Plasma concentrations of CRP |
| Tumor Necrosis Factor ⍺ (TNF-⍺) | On trial day, time 0 minutes | Plasma concentrations of TNF-⍺ |
| Interleukin 6 (IL-6) | On trial day, time 0 minutes | Plasma concentrations of IL-6 |
| Butyrate | During trial day, time 0-300 minutes | Plasma concentrations of butyrate |
| Subjective appetite - appetite questionaire | 0, 60, 120, 180, 240, 300 minutes | We will assess subjective appetite sensations with a recommended primary scale for self-reported appetite in healthy adults. The scale includes five questions addressing hunger, fullness, satiety, desire to eat and prospective consumption. The participants answer on a computer or tablet by sliding a button on a horizontal line (Visual Analog Scale) with left being eg. "Not hungry at all" to right "As hungry as I have ever felt". |
| Caloric intake | Time 300 minutes | Caloric intake (kcal) during ad libitum meal test |
| Gastric emptying assessed by acetaminophen | From ingestion of mixed meal test with acetaminophen, time 120-240 minutes | Plasma concentration of acetaminophen following oral acetaminophen intake |
| GLP-1 | During trial day, time 0-300 minutes | Plasma concentrations of GLP-1 |
| GIP | During trial day, time 0-300 minutes | Plasma concentrations of GIP |
| LEAP2 | During trial day, time 0-300 minutes | Plasma concentrations of LEAP2 |
| PYY | During trial day, time 0-300 minutes | Plasma concentrations of PYY |
| Ghrelin | During trial day, time 0-300 minutes | Plasma concentrations of ghrelin |
| Insulin | During trial day, time 0-300 minutes | Plasma concentrations of insulin |
| C-peptide | During trial day, time 0-300 minutes | Plasma concentrations of c-peptide |
| Glucagon | During trial day, time 0-300 minutes | Plasma concentrations of glucagon |
| Cardiac function | Time 0 and 90 minutes | Echocardiographic assessment of cardiac output, left ventricular ejection fraction, global longitudinal strain, tricuspid annular plane systolic excursion (TAPSE), systemic vascular resistance |
| Interleukin 10 (IL-10) | On trial day, time 0 minutes | Plasma concentrations of IL-10 |
| Microbiome composition | Day 0, 7, 14 during the 2 week period | Analysis of microbiome composition and metagenomics performed on fecal samples |
Countries
Denmark
Contacts
CONTACTSimon M Denning, MD
Outcome results
None listed