Gastro-intestinal and Hormonal Responses to Systemic Inflammatory Disease

Not Applicable

Completed

Conditions: Motility Disorder
Catabolic State
Endotoxemia

Interventions: Dietary Supplement: 3-OHB/whey
Dietary Supplement: Whey

Registration Number: NCT04056286

Lead Sponsor: University of Aarhus

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: Male

Target Recruitment: 8

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

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Catabolic + 3-OHB / Whey	3-OHB/whey	Catabolic (Inflammation (LPS) + 36 hour fast and bed rest)
Catabolic + Whey	Whey	Catabolic (Inflammation (LPS) + 36 hour fast and bed rest)
Healthy + Whey	Whey	Healthy (overnight fast)

Primary Outcome Measures

Name	Time	Method
Difference in total gastro-intestinal transit time (healthy vs catabolic conditions)	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))	Difference in total gastro-intestinal transit time measured by the Smartpill system between healthy and catabolic conditions. A pooled mean of the catabolic conditions will be used, if there is no difference between first and second exposure to LPS or "catabolic + whey" and "catabolic + 3-OHB/whey" interventions.

Secondary Outcome Measures

Name	Time	Method
Difference in gastric emptying (healthy vs catabolic conditions)	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)	Difference in gastric emptying by Smartpill between healthy and catabolic conditions. A pooled mean of the two catabolic arms during the basal period will be represented
Difference in colon passage time (healthy vs catabolic conditions)	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)	Difference in colon passage time by Smartpill between healthy and catabolic conditions. A pooled mean of the two catabolic arms during the basal period will be represented
Difference in GI motility (healthy vs catabolic conditions)	Measured from intake of the Smartpill (t = 210) until excretion with faeces (expected time frame: 2-5 days)	Difference in GI motility measured by Smartpill pressure sensor between healthy and catabolic conditions. A pooled mean of the catabolic conditions will be used, if there is no difference between first and second exposure to LPS or "catabolic + whey" and "catabolic + 3-OHB/whey" interventions. A pooled mean of the two catabolic arms during the basal period will be represented
Difference in The Pain Catastrophizing Scale (PCS) (healthy vs catabolic conditions)	Given at timepoint t = 240 minutes	Written assesment of pain-coping (score from 0-6 on each question, 0 = no worries, 6 = severe worrying). A pooled mean of the two catabolic arms during the basal period will be represented
Difference in body temperature (healthy vs catabolic conditions)	Measured from intake of the Smartpill (t = 210) until excretion with faeces (expected time frame: 2-5 days)	Difference in body temperature measured by Smartpill between healthy and catabolic conditions. A pooled mean of the two catabolic arms during the basal period will be represented
Difference in small intestine passage time (healthy vs catabolic conditions)	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)	Difference in small intestine passage time by Smartpill between healthy and catabolic conditions. A pooled mean of the two catabolic arms during the basal period will be represented
Difference in gastric- and appetite hormones (GLP-1, GIP, PYY and ghrelin) (healthy vs catabolic conditions)	Measured at baseline and 30, 60, 90, 120 and 200 minutes after the beginning of the basal period	Difference in hormones at baseline and throughout the basal period between healthy and catabolic conditions. A pooled mean of the two catabolic arms during the basal period will be represented
Difference in The Gastrointestinal Symptom Rating Scale (GSRS) (healthy vs catabolic conditions)	Given at timepoint t = 240 minutes	Written assesment of various symptoms from the GI tract by a score from 0-6 (0 = no symptoms, 6 = very severe symptoms). A pooled mean of the two catabolic arms during the basal period will be represented
Difference in pH in the ventricle, small intestine and colon (healthy vs catabolic conditions)	Measured from intake of the Smartpill (t = 210) until excretion with faeces (expected time frame: 2-5 days)	Difference in pH measured by Smartpill between healthy and catabolic conditions in the ventricle, small intestine and colon . A pooled mean of the catabolic conditions will be used, if there is no difference between first and second exposure to LPS or "catabolic + whey" and "catabolic + 3-OHB/whey" interventions. A pooled mean of the two catabolic arms during the basal period will be represented

Trial Locations

Locations (1): Medical Reasearch labaratory, DoH, Aarhus University Hospital
🇩🇰
Aarhus N, Danmark, Denmark

Gastro-intestinal and Hormonal Responses to Systemic Inflammatory Disease

Recruitment & Eligibility

Study & Design

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