Clinical trial NCT04056286: Gastro-intestinal and Hormonal Responses to Systemic Inflammatory Disease
Official title: Gastro-intestinal and Hormonal Responses to Systemic Inflammatory Disease: A Human Model Comprising Endotoxemia, Fast and Bed Rest.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Motility Disorder
Catabolic State
Endotoxemia
Keywords: gastric emptying
gastro-intestinal motility
endotoxemia
catabolism
GLP-1
GIP
Lead sponsor: University of Aarhus
Sponsor class: OTHER
Collaborators: name: Arla Food Ingrediens
name: Aarhus University Hospital
First posted: 2019-08-14
Enrollment: 8
Sex: MALE
Minimum age (years): 20
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: In a randomized crossover design, eight healthy lean young men will undergo either:

i) Healthy conditions (overnight fast) + whey protein ii) Catabolic conditions (Inflammation (LPS) + 36-hour fast and bed rest) + whey protein iii) Catabolic conditions (Inflammation (LPS) + 36-hour fast and bed rest) + 3-OHB/whey protein
Primary purpose: BASIC_SCIENCE

Brief summary: The aim of this study is to describe hormonal responses and changes of the gastrointestinal (GI) tract during healthy and catabolic inflammatory conditions.

Participants will receive isocaloric, isonitrogenous beverages of either whey or 3-OHB+whey in a randomized crossover design during either healthy (overnight fast) or catabolic conditions (inflammation/endotoxemia + 36 h fast and bed rest).

Detailed description: Background: Endotoxemia (LPS) is known to cause fever, inflammation and nausea, but the underlying mechanisms are unknown. In a human disease model comprising LPS-induced inflammation, 36 hour fast and bed rest the investigators want to investigate mechanisms accounting for the nausea and decreased food intake often observed in hospitalized patients.

Aim: This study aims to investigate total transit time and motility of the GI-tract together with the regulation of gut- and appetite hormones following catabolic conditions compared with healthy controlled conditions

Hypothesis:

Catabolic stress (endotoxemia/inflammation + 36 h fast and bed rest) induces GI-tract and hormonal changes compared with healthy conditions (overnight fast)

Interventions:

In a randomized crossover design, eight healthy, lean, young men will undergo either:

i) Healthy conditions (overnight fast) + whey protein

ii) Catabolic conditions (Inflammation (LPS) + 36-hour fast and bed rest\*) + whey protein

iii) Catabolic conditions (Inflammation (LPS) + 36-hour fast and bed rest\*) + 3-ketone/whey protein

Beverages will be isonitrogenous with 45 g whey protein + 20 g maltodextrin +/- 50 g of 3-OHB. Bolus/sip administration will be applied (1/3 bolus, 2/3 sip).Beverages will be isocaloric (fat will be added to interventions without 3-OHB)

\*LPS will be administered (1 ng/kg) the day prior to the study together with fast and bed rest. On the study day LPS (0.5 ng/kg) will be injected.

Eligibility criteria: Inclusion Criteria:

* Between 20-40 years of age
* Body mass index between 20-30 kg/m\^2
* Healthy
* Oral and written consent forms obtained prior to study day

Exclusion Criteria:

* Recent immobilization of an extremity that is not fully rehabilitated
* Lactose, lidocain or rubber allergies
* Current disease
* Use of anabolic steroids
* Smoking Former major abdominal surgery (Or current problems with the GI tract) \>10 hours of exercise/weak Present ketogenic diets or high-protein diets Blood doner that does not want to discontinue blood donations until study completion Pending MR scan

Primary outcomes:
measure: Difference in total gastro-intestinal transit time (healthy vs catabolic conditions)
timeFrame: Measured from intake of the Smartpill (together with the bolus of the protein beverages at t=210) until excretion with faeces (expected time frame: 2-5 days))
Secondary outcomes:
measure: Difference in gastric emptying (healthy vs catabolic conditions)
timeFrame: Measured from intake of the Smartpill (t = 210) until it leaves the ventricle (assessed by rise in pH levels, expected time frame: 2-7 hours)
measure: Difference in small intestine passage time (healthy vs catabolic conditions)
timeFrame: Measured from the timepoint where Smartpill leaves the ventricle until it enters the colon (assessed by specific predefined motility and pH patterns, expected timeframe 1-3 days)
measure: Difference in colon passage time (healthy vs catabolic conditions)
timeFrame: Measured from the timepoint where Smartpill leaves the small intestine until it is excreted with faeces (assessed by specific predefined motility and pH patterns, expected timeframe 1-3 days)
measure: Difference in GI motility (healthy vs catabolic conditions)
timeFrame: Measured from intake of the Smartpill (t = 210) until excretion with faeces (expected time frame: 2-5 days)
measure: Difference in body temperature (healthy vs catabolic conditions)
timeFrame: Measured from intake of the Smartpill (t = 210) until excretion with faeces (expected time frame: 2-5 days)
measure: Difference in pH in the ventricle, small intestine and colon (healthy vs catabolic conditions)
timeFrame: Measured from intake of the Smartpill (t = 210) until excretion with faeces (expected time frame: 2-5 days)
measure: Difference in gastric- and appetite hormones (GLP-1, GIP, PYY and ghrelin) (healthy vs catabolic conditions)
timeFrame: Measured at baseline and 30, 60, 90, 120 and 200 minutes after the beginning of the basal period
measure: Difference in The Gastrointestinal Symptom Rating Scale (GSRS) (healthy vs catabolic conditions)
timeFrame: Given at timepoint t = 240 minutes
measure: Difference in The Pain Catastrophizing Scale (PCS) (healthy vs catabolic conditions)
timeFrame: Given at timepoint t = 240 minutes
Other outcomes:
Locations:
city: Aarhus N
country: Denmark
facility: Medical Reasearch labaratory, DoH, Aarhus University Hospital
state: Danmark
Study officials:
affiliation: Aarhus University Hospital and Institute of Clinical Medicine
name: Niels Moeller, Professor
role: PRINCIPAL_INVESTIGATOR
References: