Chronic Mesenteric IschemiaNCT06022588
Chronic Mesenteric Ischemia Breath Testing
A study testing Sodium butyrate, 1-13C, 99%, Cambridge Isotope Laboratories, Inc.USA, U-13C6, 99%; Cambridge Isotope Laboratories, Inc.USA and Breath test in people with Chronic Mesenteric Ischemia, run by Erasmus Medical Center at 1 site in Netherlands.
Trial 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… Read more about this study
- Who is it for?
- Any ageHealthy volunteers can take part
- Conditions the study is for
- Chronic Mesenteric Ischemia
- What is being tested?
- Sodium butyrate, 1-13C, 99%, Cambridge Isotope Laboratories, Inc.USA, U-13C6, 99%; Cambridge Isotope Laboratories, Inc.USA and Breath test
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 20 participants
- Where
- 1 siteNetherlands
- Study dates
- 1 Mar 2021to 1 Aug 2021
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
Who may be able to join
- healthy volunteers without any gastrointestinal complaints
Who cannot join
- pregnant woman
Trial locations and contacts
1 site in 1 country.
Netherlands1 site
Erasmus Medical Center - Department of Gastroenterology
Rotterdam
About this study
Official title: Heavy Isotope-labeled-butyrate and Glucose in Breath Testing to Detect Mesenteric Ischemia, a Proof-of-concept Study in Healthy Volunteers.
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.
Read more
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.
Read the detailed description
Even as chronic mesenteric ischemia (CMI) is the most common vascular disorder involving the mesenteric arteries, accounting for 2% of all revascularization procedures, it remains an underdiagnosed condition. CMI is an invalidating disease that causes severe complaints of post-prandial abdominal pain, food fear and weight loss. Diagnosis of CMI remains difficult since no gold standard diagnostic test exists, the presumptive diagnosis of CMI is currently confirmed when a patient experiences relief of symptoms after revascularization. For making treatment decisions, clinicians rely on a consensus diagnosis, based on clinical history, presence of mesenteric artery stenosis on abdominal imaging, and, in dedicated centers, the outcome of a functional test, such as visible light spectroscopy (VLS) or tonometry. The diagnostic accuracy of this consensus diagnosis is unstatisfactory, since clinical improvement is achieved in only 73% of patients with a consensus diagnosis of CMI based on a single mesenteric artery stenosis. Per extenso in the remaining 27% treatment was initiated in patients not suffering from CMI. Stressing the need for a reliable diagnostic test to identify patients with CMI.
In the intestinal epithelium the most important substrate for mitochondrion-dependent ATP production, and by consequence as the source for CO2 release is butyrate, a small chain fatty acid produced by the intestinal microflora. Under ischemic conditions, butyrate can no longer be metabolized. The most straight forward biochemical pathway to cope with this situation is a switch in cellular metabolism to anaerobic glycolysis. In this process glucose is metabolized to pyruvate, producing two ATP molecules, providing an oxygen independent pathway for maintaining ATP production, but also resulting in the reduction of NAD+ molecules into NADH+. To maintain ATP production, pyruvate will undergo a process called fermentation resulting in the production of lactate in which NADH+ is recycled back to NAD+ so that glycolysis can continue. Upon subsequent transport via the blood, lactate is cleared in the liver and the resulting CO2 will leave the body via the lungs. Hence theoretically measuring the shift from butyrate towards glucose metabolism, which occurs in enterocytes under anaerobic conditions, could be a method to detect mucosal ischemia.
This multi-center randomized interventional proof of principal study explored the possibility to quantify mucosal oxygen content by labeled-butyrate and labelled-glucose breath testing as a potential test to diagnose CMI. Since both substrates are dependent on oxygen to be metabolized, it is expected that subjects with low mucosal oxygen concentrations will metabolize less butyrate and glucose compared to subjects with normal mucosal oxygen concentrations.
- Conditions
- Chronic Mesenteric Ischemia
- Being tested
- Sodium butyrate, 1-13C, 99%, Cambridge Isotope Laboratories, Inc.USA, U-13C6, 99%; Cambridge Isotope Laboratories, Inc.USA, Breath test, Exercise + breath test
- Keywords
- Chronic mesenteric ischemia, Diagnostic, Breath test
- Medical subject headings
- Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Sodium butyrate, 1-13C, 99%, Cambridge Isotope Laboratories, Inc.USADrug
Also called 13C butyrate
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
U-13C6, 99%; Cambridge Isotope Laboratories, Inc.USADrug
Also called 13C glucose
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
Breath testDiagnostic 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‰).
Exercise + breath testDiagnostic 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
| Study group | Role | What they receive |
|---|---|---|
| 13C -butyrate control group | Placebo comparator | 5 healthy volunteers performed the breath test without any psychical exercise Receives: Drug: Sodium butyrate, 1-13C, 99%, Cambridge Isotope Laboratories, Inc.USA; Diagnostic Test: Breath test |
| 13C -butyrate intervention group | Experimental | 5 healthy volunteers performed the breath test with psychical exercise - bicycle test Receives: Drug: Sodium butyrate, 1-13C, 99%, Cambridge Isotope Laboratories, Inc.USA; Diagnostic Test: Exercise + breath test |
| 13C -glucose control group | Placebo comparator | 5 healthy volunteers performed the breath test without any psychical exercise Receives: Drug: U-13C6, 99%; Cambridge Isotope Laboratories, Inc.USA; Diagnostic Test: Exercise + breath test |
| 13C -glucose intervention group | Experimental | 5 healthy volunteers performed the breath test with psychical exercise - bicycle test Receives: Drug: U-13C6, 99%; Cambridge Isotope Laboratories, Inc.USA; Diagnostic Test: Exercise + breath test |
What is being measured
The primary outcome is the main question the study is designed to answer.
The median concentrations of measured 13CO2
The median concentrations of measured 13CO2 at each time point where compared within the four groups and statistically tested with a Mann - Whitney U test.
Measured: 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 (total of 12 time points) after ingestion of 13C-butyrate or 13C-glucose.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Sep 2023
- Study start1 Mar 2021
- Primary completion1 Apr 2021
- Study completion1 Aug 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Chronic Mesenteric IschemiaStudies of the same condition, open and under way.
- More trials run by Erasmus Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Erasmus Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Marco J. Bruno, Erasmus Medical Center
- Investigators
- Marco Bruno, prof., Principal investigator, Erasmus Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06022588
- Sponsor's protocol ID
- NL72878.078.20
- Status last verified
- Aug 2023
- First submitted
- 26 Jul 2023
- Last updated
- 5 Sep 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Sep 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Heavy Isotope-labeled-butyrate and Glucose in Breath Testing to Detect Mesenteric Ischemia, a Proof-of-concept Study in Healthy Volunteers.
- ClinicalTrials.gov ID
- NCT06022588
- Acronym / sponsor ID
- NL72878.078.20
- Conditions
- Chronic Mesenteric Ischemia
- Keywords
- Chronic mesenteric ischemia, Diagnostic, Breath test
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Erasmus Medical CenterUniversity, hospital or other
- Study start
- 1 Mar 2021 (actual)
- Primary completion
- 1 Apr 2021 (actual)
- Study completion
- 1 Aug 2021 (actual)
- First posted
- 5 Sep 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Even as chronic mesenteric ischemia (CMI) is the most common vascular disorder involving the mesenteric arteries, accounting for 2% of all revascularization procedures, it remains an underdiagnosed condition. CMI is an invalidating disease that causes severe complaints of post-prandial abdominal pain, food fear and weight loss. Diagnosis of CMI remains difficult since no gold standard diagnostic test exists, the presumptive diagnosis of CMI is currently confirmed when a patient experiences relief of symptoms after revascularization. For making treatment decisions, clinicians rely on a consensus diagnosis, based on clinical history, presence of mesenteric artery stenosis on abdominal imaging, and, in dedicated centers, the outcome of a functional test, such as visible light spectroscopy (VLS) or tonometry. The diagnostic accuracy of this consensus diagnosis is unstatisfactory, since clinical improvement is achieved in only 73% of patients with a consensus diagnosis of CMI based on a single mesenteric artery stenosis. Per extenso in the remaining 27% treatment was initiated in patients not suffering from CMI. Stressing the need for a reliable diagnostic test to identify patients with CMI.
In the intestinal epithelium the most important substrate for mitochondrion-dependent ATP production, and by consequence as the source for CO2 release is butyrate, a small chain fatty acid produced by the intestinal microflora. Under ischemic conditions, butyrate can no longer be metabolized. The most straight forward biochemical pathway to cope with this situation is a switch in cellular metabolism to anaerobic glycolysis. In this process glucose is metabolized to pyruvate, producing two ATP molecules, providing an oxygen independent pathway for maintaining ATP production, but also resulting in the reduction of NAD+ molecules into NADH+. To maintain ATP production, pyruvate will undergo a process called fermentation resulting in the production of lactate in which NADH+ is recycled back to NAD+ so that glycolysis can continue. Upon subsequent transport via the blood, lactate is cleared in the liver and the resulting CO2 will leave the body via the lungs. Hence theoretically measuring the shift from butyrate towards glucose metabolism, which occurs in enterocytes under anaerobic conditions, could be a method to detect mucosal ischemia.
This multi-center randomized interventional proof of principal study explored the possibility to quantify mucosal oxygen content by labeled-butyrate and labelled-glucose breath testing as a potential test to diagnose CMI. Since both substrates are dependent on oxygen to be metabolized, it is expected that subjects with low mucosal oxygen concentrations will metabolize less butyrate and glucose compared to subjects with normal mucosal oxygen concentrations.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| 13C -butyrate control group | Placebo comparator | Drug: Sodium butyrate, 1-13C, 99%, Cambridge Isotope Laboratories, Inc.USA, Diagnostic Test: Breath test5 healthy volunteers performed the breath test without any psychical exercise |
| 13C -butyrate intervention group | Experimental | Drug: Sodium butyrate, 1-13C, 99%, Cambridge Isotope Laboratories, Inc.USA, Diagnostic Test: Exercise + breath test5 healthy volunteers performed the breath test with psychical exercise - bicycle test |
| 13C -glucose control group | Placebo comparator | Drug: U-13C6, 99%; Cambridge Isotope Laboratories, Inc.USA, Diagnostic Test: Exercise + breath test5 healthy volunteers performed the breath test without any psychical exercise |
| 13C -glucose intervention group | Experimental | Drug: U-13C6, 99%; Cambridge Isotope Laboratories, Inc.USA, Diagnostic Test: Exercise + breath test5 healthy volunteers performed the breath test with psychical exercise - bicycle test |
Who may qualify
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (1 listed)
- healthy volunteers without any gastrointestinal complaints
Key exclusion criteria (1 listed)
- pregnant woman
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Sodium butyrate, 1-13C, 99%, Cambridge Isotope Laboratories, Inc.USAAlso: 13C butyratea 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 | 13C -butyrate control group, 13C -butyrate intervention group |
| U-13C6, 99%; Cambridge Isotope Laboratories, Inc.USAAlso: 13C glucosea 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 | Drug | 13C -glucose control group, 13C -glucose intervention group |
| Breath testBreath 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 | 13C -butyrate control group |
| Exercise + breath testThe 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 | Diagnostic test | 13C -butyrate intervention group, 13C -glucose control group, 13C -glucose intervention group |
Primary outcome
The median concentrations of measured 13CO2
Time frame: 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 (total of 12 time points) after ingestion of 13C-butyrate or 13C-glucose.
The median concentrations of measured 13CO2 at each time point where compared within the four groups and statistically tested with a Mann - Whitney U test.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Sep 2023.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Marco Bruno, prof. principal investigator
Erasmus Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Sodium butyrate, 1-13C, 99%, Cambridge Isotope Laboratories, Inc.USA, U-13C6, 99%; Cambridge Isotope Laboratories, Inc.USA and Breath test in people with Chronic Mesenteric Ischemia, run by Erasmus Medical Center at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 Sep 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The median concentrations of measured 13CO2 (time frame: 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 (total of 12 time points) after ingestion of 13C-butyrate or 13C-glucose.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Sep 2023.