Gastro-intestinal and Hormonal Responses to Systemic Inflammatory Disease

Endotoxemia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04056286
• Other study ID #: Ketone Gastro study
• Status: Completed
• Phase: N/A
• Start date: June 17, 2019
• Est. completion date: January 23, 2020

Study information

• Verified date: July 2019
• Source: University of Aarhus
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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 information / eligibility

• Status: Completed
• Enrollment: 8
• Est. completion date: January 23, 2020
• Est. primary completion date: January 23, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 20 Years to 40 Years

Eligibility

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

Related Conditions & MeSH terms

• Catabolic State
• Endotoxemia
• Motility Disorder

Intervention

Dietary Supplement:
• Whey
45 g whey protein + 20 g maltodextrin
• 3-OHB/whey
50 g 3-OHB + 45 g whey protein + 20 g maltodextrin

Locations

Country	Name	City	State
Denmark	Medical Reasearch labaratory, DoH, Aarhus University Hospital	Aarhus N	Danmark

Sponsors (3)

Lead Sponsor	Collaborator
University of Aarhus	Aarhus University Hospital, Arla Food Ingrediens

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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
Secondary	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
Secondary	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