- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05160077
Optoacoustic Characterization of Postprandial Intestinal Blood Flow (NEPOMUC)
Noninvasive Characterization of Postprandial Intestinal Blood Flow Using Multispectral Optoacoustic Tomography
Inflammatory activities in the gastrointestinal tract are accompanied by an increase in blood flow in the intestinal wall layers of the respective organs. Also in chronic inflammatory bowel diseases, the release of vasoactive inflammatory mediators leads to vasodilation and consecutive increase of blood flow in the bowel wall. So far, these changes in blood flow can be detected by power Doppler sonography without being part of routine clinical diagnostics. Another promising option for non-invasive measurement of blood flow in the intestinal wall is Multispectral Optoacoustic Tomography (MSOT). Previous studies have shown that MSOT can be used to quantitatively measure hemoglobin in the bowel wall and thus provide information on blood flow and inflammatory activity in the intestines of patients with Crohn's disease. This is currently being further investigated in a pivotal study (Euphoria, H2020) and could lead to the possibility of non-invasive assessment of disease activity in inflammatory bowel disease (IBD) in the future.
The regional blood flow in the intestinal wall and the distribution of gastrointestinal blood flow are also subject to strong postprandial changes. During absorption of food components, blood flow increases sequentially in the respective sections of the gastrointestinal tract, leading to postprandial hyperemia. Because postprandial hyperemia is particularly regulated locally by the presence of dietary components, there is a relationship between the sequential increase in blood flow in the intestinal wall and the peristaltic transport of chyme through the gastrointestinal tract. Postprandial hyperemia could also lead to an increase in the optoacoustic hemoglobin signal of the intestinal wall and thus have an impact on the assessment of inflammatory activity in IBD using MSOT. Additionally, MSOT allows the identification of non-absorbable exogenous chromophores, such as indocyanine green (ICG), which could allow co-localization of the chyme in the intestinal lumen after oral application of ICG.
This pilot study investigates whether postprandial blood flow changes can be quantitatively measured using MSOT and whether these changes occur simultaneously with the gastrointestinal passage of the chyme as measured by the ICG signal in the intestinal lumen.
Study Overview
Status
Intervention / Treatment
Detailed Description
The gastrointestinal tract essentially fulfills two major functions: digestion and absorption of food, and physical and immunological barrier against environmental influences. These basic functions are critically dependent on splanchnic blood flow at both the macrovascular and microvascular levels. In particular, advances in vascular biology have revealed a central and intricate role of blood circulation in inflammatory bowel disease (IBD).
Until now, changes in blood flow have been used as surrogate markers for altered inflammatory activity in the intestine, e.g., by Doppler sonographic detection. Multispectral Optoacoustic Tomograph (MSOT) allows for non-invasive, quantitative imaging of the molecular composition of target tissues. In MSOT, similar to conventional sonography, a transducer is placed on the skin but energy is delivered to the tissue by means of laser light in the near infrared spectrum instead of ultrasound waves. This leads to a constant alternation of minimal expansions and contractions (thermoelastic expansion) of individual tissue components or molecules. The resulting ultrasound waves can subsequently be detected by the same examination unit. Previous studies have shown that quantitative determination of hemoglobin can provide information on blood flow and inflammatory activity in the intestine of adult patients with Crohn's disease. In particular, the distinction between the activity levels of the disease (remission/low/moderate/high) is promising for saving invasive measures in the future when evaluating the progression of the disease.
In addition to inflammatory processes, food intake also causes fluctuations in regional blood flow in the gastrointestinal tract. This manifests as postprandial hyperemia, which occurs sequentially in the different sections of the gastrointestinal tract from oral to aboral.
The time course of postprandial hyperemia in the different sections of the gastrointestinal tract has been scientifically investigated in many studies. While an increase in blood flow in the stomach and duodenum can be detected after 30-60 minutes, it takes much longer for postprandial hyperemia to be detected in the areas used to measure inflammatory activity with MSOT in IBD such as the terminal ileum and sigmoid colon. An increase in blood flow in the ileum can be measured after 120 minutes at the earliest, and the arrival of chyme in the colon and the accompanying local increase in blood flow occur after approximately 240-300 minutes.
It is unclear whether this postprandial hyperemia can lead to a change and potential increase in the optoacoustic hemoglobin signal of the intestinal wall, resulting in falsely high MSOT signals in the determination of inflammatory activity. This study investigates influences of a standardized dietary on the MSOT signal of the intestinal wall using a longitudinal design. Optoacoustic signals will be compared between subjects in fasting and postprandial states. Because the postprandial increase in intestinal blood flow is predominantly a result of the local presence of chyme in the intestine, a simultaneous determination of intestinal transit of chyme during MSOT measurement would be helpful to validate whether postprandial changes in MSOT signals are attributable to hyperemia in the corresponding bowel segment. Besides imaging of hemoglobin, MSOT enables the detection of exogenous chromophores (i.e. dyes). In this study, the oral administration of the nonabsorbable dye indocyanine green (ICG) will be used for noninvasive identification of the chyme. The combination of exogenous and endogenous chromophores thus allows accurate co-localization and registration of intestinal wall blood flow patterns and chyme transit. This information enables accurate anatomical mapping of interfering influences on the determination of hemoglobin using MSOT.
Study Type
Enrollment (Actual)
Phase
- Not Applicable
Contacts and Locations
Study Locations
-
-
Bavaria
-
Erlangen, Bavaria, Germany, 91054
- University Hospital Erlangen
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Age over 18 years
- Written declaration of consent
Exclusion Criteria:
Generally valid:
- Pregnancy
- Nursing mothers
- Tattoo in the field of investigation
- Subcutaneous fat tissue over 3 cm
- Chronic or acute diseases of the gastrointestinal tract or symptoms suggestive of such a disease
- Diseases requiring acute treatment
- Lack of written consent
ICG related:
- Known hypersensitivity to ICG, sodium iodide or iodine
- Hyperthyroidism, focal or diffuse thyroid autonomy
- Treatment with radioactive iodine for the diagnostic examination of thyroid function within two weeks before or after the study
- Restricted renal function
- Intake of the following drugs: Beta-blockers, anticonvulsants, cyclopropane, bisulphite compounds, haloperidol, heroin, meperidine, metamizole, methadone, morphine, nitrofurantoin, opium alkaloids, phenobarbital, phenylbutazone, probenecid, rifamycin, any injection containing sodium bisulphite.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: DIAGNOSTIC
- Allocation: NON_RANDOMIZED
- Interventional Model: CROSSOVER
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
OTHER: Fasting
All examinations are in a fasting state.
|
MSOT Acuity Echo, iThera medical, Munich
|
OTHER: Standardised Breakfast
Preprandial examination is in fasting state, all postprandial examinations will be conducted with standardized dietary. 30 minutes after the beginning of the preprandial examination participants receive an standardized breakfast. 270 minutes after the beginning of the preprandial examination participants receive an standardised meal. |
MSOT Acuity Echo, iThera medical, Munich
|
OTHER: Standardised Breakfast and ICG
Preprandial examination are in a fasting state, all postprandial examinations will be conducted with standardized dietary including indocyanine green (ICG) dye. 30 minutes after the beginning of the preprandial examination participants receive an standardised breakfast containing ICG. 270 minutes after the beginning of the preprandial examination participants receive an standardised meal without ICG. |
MSOT Acuity Echo, iThera medical, Munich
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change of the quantitative de-/oxygenated hemoglobin signal (in arbitrary units)
Time Frame: every 60 minutes over 8 hours on each of the three examination days
|
Change of the quantitative de-/oxygenated hemoglobin signal in the wall of the gastrointestinal tract (gastric antrum, terminal ileum, transverse colon, and sigmoid colon) over a postprandial time of 7 hours.
|
every 60 minutes over 8 hours on each of the three examination days
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change of the qualitative and quantitative ICG signal (in arbitrary units)
Time Frame: every 60 minutes over 8 hours on on the third examination day
|
Change of the qualitative and quantitative ICG signal (in arbitrary units) in the lume of the gastrointestinal tract (gastric antrum, terminal ileum, transverse colon, and sigmoid colon) over a postprandial time of 7 hours.
|
every 60 minutes over 8 hours on on the third examination day
|
Change of the quantitative single wavelengths signal (in arbitrary units)
Time Frame: every 60 minutes over 8 hours on each of the three examination days
|
Change of the quantitative single wavelengths signal (in arbitrary units) in the wall of the gastrointestinal tract (gastric antrum, terminal ileum, transverse colon, and sigmoid colon) over a postprandial time of 7 hours.
|
every 60 minutes over 8 hours on each of the three examination days
|
Change of the optoacoustic spectrum (in arbitrary units, normalized)
Time Frame: every 60 minutes over 8 hours on each of the three examination days
|
Change of the optoacoustic spectrum (in arbitrary units, normalized) in the wall of the gastrointestinal tract (gastric antrum, terminal ileum, transverse colon, and sigmoid colon) over a postprandial time of 7 hours.
|
every 60 minutes over 8 hours on each of the three examination days
|
Change of Blood flow in the big splanchnic arteries.
Time Frame: every 60 minutes over 8 hours on each of the three examination days
|
Change of Blood flow in the coeliac trunk, superior mesenteric artery, inferior mesenteric artery measured by Doppler sonography over a postprandial time of 7 hours.
|
every 60 minutes over 8 hours on each of the three examination days
|
Change of Resistance Index in the big splanchnic arteries.
Time Frame: every 60 minutes over 8 hours on each of the three examination days
|
Change of Resistance Index in the coeliac trunk, superior mesenteric artery, inferior mesenteric artery measured by Doppler sonography over a postprandial time of 7 hours.
|
every 60 minutes over 8 hours on each of the three examination days
|
Change of Pulsatility Index in the big splanchnic arteries.
Time Frame: every 60 minutes over 8 hours on each of the three examination days
|
Change of Pulsatility Index in the coeliac trunk, superior mesenteric artery, inferior mesenteric artery measured by Doppler sonography over a postprandial time of 7 hours.
|
every 60 minutes over 8 hours on each of the three examination days
|
Change of peak systolic velocity in the big splanchnic arteries.
Time Frame: every 60 minutes over 8 hours on each of the three examination days
|
Change of peak systolic velocity in the coeliac trunk, superior mesenteric artery, inferior mesenteric artery measured by Doppler sonography over a postprandial time of 7 hours.
|
every 60 minutes over 8 hours on each of the three examination days
|
Change of end diastolic velocity in the big splanchnic arteries.
Time Frame: every 60 minutes over 8 hours on each of the three examination days
|
Change of end diastolic velocity in the coeliac trunk, superior mesenteric artery, inferior mesenteric artery measured by Doppler sonography over a postprandial time of 7 hours.
|
every 60 minutes over 8 hours on each of the three examination days
|
Collaborators and Investigators
Publications and helpful links
General Publications
- Matheson PJ, Wilson MA, Garrison RN. Regulation of intestinal blood flow. J Surg Res. 2000 Sep;93(1):182-96. doi: 10.1006/jsre.2000.5862.
- Deban L, Correale C, Vetrano S, Malesci A, Danese S. Multiple pathogenic roles of microvasculature in inflammatory bowel disease: a Jack of all trades. Am J Pathol. 2008 Jun;172(6):1457-66. doi: 10.2353/ajpath.2008.070593. Epub 2008 May 5.
- Calabrese E, Maaser C, Zorzi F, Kannengiesser K, Hanauer SB, Bruining DH, Iacucci M, Maconi G, Novak KL, Panaccione R, Strobel D, Wilson SR, Watanabe M, Pallone F, Ghosh S. Bowel Ultrasonography in the Management of Crohn's Disease. A Review with Recommendations of an International Panel of Experts. Inflamm Bowel Dis. 2016 May;22(5):1168-83. doi: 10.1097/MIB.0000000000000706.
- Ntziachristos V, Razansky D. Molecular imaging by means of multispectral optoacoustic tomography (MSOT). Chem Rev. 2010 May 12;110(5):2783-94. doi: 10.1021/cr9002566. No abstract available.
- Weber J, Beard PC, Bohndiek SE. Contrast agents for molecular photoacoustic imaging. Nat Methods. 2016 Jul 28;13(8):639-50. doi: 10.1038/nmeth.3929.
- Regensburger AP, Brown E, Kronke G, Waldner MJ, Knieling F. Optoacoustic Imaging in Inflammation. Biomedicines. 2021 Apr 28;9(5):483. doi: 10.3390/biomedicines9050483.
- Knieling F, Neufert C, Hartmann A, Claussen J, Urich A, Egger C, Vetter M, Fischer S, Pfeifer L, Hagel A, Kielisch C, Gortz RS, Wildner D, Engel M, Rother J, Uter W, Siebler J, Atreya R, Rascher W, Strobel D, Neurath MF, Waldner MJ. Multispectral Optoacoustic Tomography for Assessment of Crohn's Disease Activity. N Engl J Med. 2017 Mar 30;376(13):1292-1294. doi: 10.1056/NEJMc1612455. No abstract available.
- Waldner MJ, Knieling F, Egger C, Morscher S, Claussen J, Vetter M, Kielisch C, Fischer S, Pfeifer L, Hagel A, Goertz RS, Wildner D, Atreya R, Strobel D, Neurath MF. Multispectral Optoacoustic Tomography in Crohn's Disease: Noninvasive Imaging of Disease Activity. Gastroenterology. 2016 Aug;151(2):238-40. doi: 10.1053/j.gastro.2016.05.047. Epub 2016 Jun 3. No abstract available.
- Goertz RS, Egger C, Neurath MF, Strobel D. Impact of food intake, ultrasound transducer, breathing maneuvers and body position on acoustic radiation force impulse (ARFI) elastometry of the liver. Ultraschall Med. 2012 Aug;33(4):380-5. doi: 10.1055/s-0032-1312816. Epub 2012 Jun 21.
- Kvietys PR. The Gastrointestinal Circulation. San Rafael (CA): Morgan & Claypool Life Sciences; 2010. Available from http://www.ncbi.nlm.nih.gov/books/NBK53092/
- Sou S, Matsui T, Yao T, Naito M, Yorioka M, Beppu T, Nagahama T, Futami K. Differentiating enterocutaneous fistulae from suture abscesses complicating Crohn's disease using oral administration of indocyanine green. J Gastroenterol Hepatol. 2006 Dec;21(12):1850-3. doi: 10.1111/j.1440-1746.2006.04287.x.
- Bennink R, Peeters M, Van den Maegdenbergh V, Geypens B, Rutgeerts P, De Roo M, Mortelmans L. Evaluation of small-bowel transit for solid and liquid test meal in healthy men and women. Eur J Nucl Med. 1999 Dec;26(12):1560-6. doi: 10.1007/s002590050495.
- Camilleri M, Colemont LJ, Phillips SF, Brown ML, Thomforde GM, Chapman N, Zinsmeister AR. Human gastric emptying and colonic filling of solids characterized by a new method. Am J Physiol. 1989 Aug;257(2 Pt 1):G284-90. doi: 10.1152/ajpgi.1989.257.2.G284.
Study record dates
Study Major Dates
Study Start (ACTUAL)
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ACTUAL)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- 346_21 B
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
IPD Sharing Time Frame
IPD Sharing Access Criteria
The data sets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request as follows:
- Individual participant data will not be available
- Study Protocol Plan will be available
- The data will be available beginning 9 months and ending 36 months following article publication.
- The data will be available to researchers who provide a methodologically sound proposal.
- The data will be available for individual participant data meta-analysis, only.
- Proposals may be submitted up to 36 months following article publication. After 36 months the data will be available in our University's data warehouse but without investigator support other than deposited metadata. Information regarding submitting proposals and accessing data may be found at www.uk-erlangen.de.
Restrictions may apply due to patient privacy and the General Data Protection Regulation.
IPD Sharing Supporting Information Type
- STUDY_PROTOCOL
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Inflammatory Bowel Diseases
-
University of British ColumbiaCompletedInflammatory Bowel Disease 11Canada
-
University of ChicagoTerminatedInflammatory Bowel Disease (IBD)United States
-
Centre Hospitalier Universitaire, AmiensFunding from DGOS (PHRC IR 2013 and PRME)CompletedPediatric Inflammatory Bowel DiseaseFrance
-
University of Wisconsin, MadisonTerminatedInflammatory Bowel Disease (IBD)United States
-
Cedars-Sinai Medical CenterUnknownPediatric Inflammatory Bowel Disease
-
University of Wisconsin, MadisonCompletedInflammatory Bowel Disease (IBD)United States
-
Assiut UniversityNot yet recruitingIBD-Inflammatory Bowel Disease
-
Icahn School of Medicine at Mount SinaiNorthwestern University; The Cleveland Clinic; University of California, Davis; RxHealt...RecruitingInflammatory Bowel Disease (IBD)United States
-
Nemours Children's ClinicNASPGHAN FoundationCompletedInflammatory Bowel Disease (IBD)United States
-
Hull University Teaching Hospitals NHS TrustWellcome/EPSRC Centre for Interventional and Surgical Sciences, University...RecruitingInflammatory Bowel Disease 1United Kingdom
Clinical Trials on Multispectral optoacoustic tomography (MSOT)
-
University of Erlangen-Nürnberg Medical SchoolNot yet recruiting
-
Ulrich RotherPD Dr. med. Ferdinand Knieling, Department of pediatrics, University of Erlangen-NürnbergRecruitingPeripheral Arterial Disease | Peripheral Vascular Diseases | Intermittent ClaudicationGermany
-
iThera Medical GmbHEuropean CommissionSuspendedInflammatory Bowel Diseases | Crohn Disease | Ulcerative ColitisGermany, Italy
-
University Hospital ErlangenDepartment of Pediatrics and Adolescent Medicine, University Hospital Erlangen... and other collaboratorsActive, not recruitingPeripheral Arterial Disease | Peripheral Vascular DiseasesGermany
-
University of Erlangen-Nürnberg Medical SchoolCompletedMuscular Diseases | Spinal Muscular AtrophyGermany
-
University of Erlangen-Nürnberg Medical SchooliThera Medical GmbHCompletedCrohn's Disease | Ulcerative Colitis | IBDGermany
-
University of Erlangen-Nürnberg Medical SchoolRecruitingPompe Disease (Late-onset) | Pompe Disease | Pompe's Disease Juvenile Onset | Pompe Disease Infantile-OnsetGermany
-
Memorial Sloan Kettering Cancer CenterRecruitingMelanoma | Breast CancerUnited States, Germany
-
University of Erlangen-Nürnberg Medical SchoolUnknownMuscular Diseases | Spinal Muscular AtrophyGermany
-
University of Erlangen-Nürnberg Medical SchoolCompletedCrohn's Disease | Ulcerative Colitis | IBDGermany