Chronic Mesenteric Ischemia Breath Testing

Summary

Background and aims:

A gold standard diagnostic test to diagnose chronic mesenteric ischemia is currently lacking. Isotope labelled-butyrate and glucose breath testing could theoretically quantify mucosal oxygen consumption and thereby detect ischemia, since oxygen is needed to absorb and metabolize butyrate and glucose, and distinguish aerobic/anaerobic intestinal epithelial metabolism. Here we aim to test this notion and compare results to conventional biomarkers.

Methods:

Healthy volunteers were randomized into two control groups and two intervention groups, each consisting of five volunteers receiving either oral 13C -butyrate or 13C -glucose. The control groups performed breath tests without any physical exercise. The intervention groups performed a 30 minutes standardized bicycle exercise test, which has been proven to elicit mesenteric ischemia. Breath samples of expired 13CO2 were collected during a period of 4 hours and results were contrasted to measurements of biomarkers in peripheral blood.

Conditions

• Chronic Mesenteric Ischemia

Interventions

DRUG

Sodium butyrate, 1-13C, 99%, Cambridge Isotope Laboratories, Inc.USA

a solution containing butyrate of which 12C of the last 4 carbon positions of butyrate were replaced by 13C butyrate. Participants received 0.80 gram 13C-butyrate (7.3 mMol butyrate / 29 mMol 13C) dissolved in 50 mL water at baseline

DRUG

U-13C6, 99%; Cambridge Isotope Laboratories, Inc.USA

a glucose solution in which all six 12C carbons were replaced by 13C D-Glucose. Participants received 0.75 gram 13C-glucose (4.2 mMol D-glucose/ 25 mMol 13C) dissolved in 50 mL water at baseline

DIAGNOSTIC_TEST

Breath test

Breath tests were performed at the following time points baseline, 0.5, 1, 1.25 1.5, 1.75, 2, 2.25, 2.5, 3, 3.5 and 4 hours after ingestion of 13C-butyrate and 13C-glucose. Breath samples were obtained by blowing a single breath of air through a straw into a test tube. Two breath samples were collected at all mentioned time points. Measurement of 13CO2 is performed using mass spectrometry (IDMicro Breath, Compact Science Systems, Newcastle-Under-Lyme, United Kingdom) using procedures described earlier for galactose and methacetin breath tests, and expressed as an absolute increase in the 13CO2-to-12CO2 ratio in delta permil (δ‰).

DIAGNOSTIC_TEST

Exercise + breath test

The intervention groups performed a standardized bicycle ergometer exercise test of 30 minutes and semi-continuous peripheral blood lactate monitoring. The bicycle ergometer protocol consists of three phases. The first 10 minutes of exercise was used to gradually increase the workload until submaximal exercise intensity was reached which is defined as a circulating blood lactate level between 3 and 5.5 mmol/L. From minute 10 to 20 submaximal exercise intensity was maintained by adjusting the workload based on lactate measurements. Minute 20 to 30 was used to reach maximal exercise intensity, the workload was increased by 10% of the submaximal workload until exhaustion

Sponsors & Collaborators

• Erasmus Medical Center

  lead OTHER

Principal Investigators

• Marco Bruno, prof. · Erasmus Medical Center

Study Design

Allocation

RANDOMIZED

Purpose

DIAGNOSTIC

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2021-03-01

Primary Completion

2021-04-01

Completion

2021-08-01

Countries

• Netherlands

Study Locations