Gastro-intestinal and Hormonal Responses to Systemic Inflammatory Disease

Gastro-intestinal and Hormonal Responses to Systemic Inflammatory Disease: A Human Model Comprising Endotoxemia, Fast and Bed Rest.

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).

Study Overview

• Status: Completed
• Conditions: Endotoxemia; Motility Disorder; Catabolic State
• Intervention / Treatment: Dietary supplement: Whey; Dietary supplement: 3-OHB/whey

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.

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Denmark
  • Danmark
    • Aarhus N, Danmark, Denmark, 8200
      • Medical Reasearch labaratory, DoH, Aarhus University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 40 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: SINGLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Healthy + Whey; Healthy (overnight fast)	Dietary supplement: Whey; 45 g whey protein + 20 g maltodextrin
EXPERIMENTAL: Catabolic + Whey; Catabolic (Inflammation (LPS) + 36 hour fast and bed rest)	Dietary supplement: Whey; 45 g whey protein + 20 g maltodextrin
EXPERIMENTAL: Catabolic + 3-OHB / Whey; Catabolic (Inflammation (LPS) + 36 hour fast and bed rest)	Dietary supplement: 3-OHB/whey; 50 g 3-OHB + 45 g whey protein + 20 g maltodextrin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Difference in total gastro-intestinal transit time (healthy vs catabolic conditions)	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.	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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Difference in gastric emptying (healthy vs catabolic conditions)	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	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 small intestine passage time (healthy vs catabolic conditions)	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	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 colon passage time (healthy vs catabolic conditions)	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	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 GI motility (healthy vs catabolic conditions)	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	Measured from intake of the Smartpill (t = 210) until excretion with faeces (expected time frame: 2-5 days)
Difference in body temperature (healthy vs catabolic conditions)	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	Measured from intake of the Smartpill (t = 210) until excretion with faeces (expected time frame: 2-5 days)
Difference in pH in the ventricle, small intestine and colon (healthy vs catabolic conditions)	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	Measured from intake of the Smartpill (t = 210) until excretion with faeces (expected time frame: 2-5 days)
Difference in gastric- and appetite hormones (GLP-1, GIP, PYY and ghrelin) (healthy vs catabolic conditions)	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	Measured at baseline and 30, 60, 90, 120 and 200 minutes after the beginning of the basal period
Difference in The Gastrointestinal Symptom Rating Scale (GSRS) (healthy vs catabolic conditions)	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	Given at timepoint t = 240 minutes
Difference in The Pain Catastrophizing Scale (PCS) (healthy vs catabolic conditions)	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	Given at timepoint t = 240 minutes

Collaborators and Investigators

• Sponsor: University of Aarhus
• Collaborators: Aarhus University Hospital; Arla Food Ingrediens

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 17, 2019
• Primary Completion (ACTUAL): January 23, 2020
• Study Completion (ACTUAL): January 23, 2020

Study Registration Dates

• First Submitted: July 29, 2019
• First Submitted That Met QC Criteria: August 13, 2019
• First Posted (ACTUAL): August 14, 2019

Study Record Updates

• Last Update Posted (ACTUAL): June 11, 2020
• Last Update Submitted That Met QC Criteria: June 9, 2020
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Keywords: GLP-1; gastric emptying; GIP; endotoxemia; gastro-intestinal motility; catabolism
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Sepsis; Bacteremia; Toxemia; Endotoxemia
• Other Study ID Numbers: Ketone Gastro study

Drug and device information, study documents

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