Optoacoustic Characterization of Postprandial Intestinal Blood Flow

NCT ID: NCT05160077

Last Updated: 2022-07-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 10 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-11-23
• Study Completion Date: 2022-01-15

Brief Summary

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.

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.

Conditions

Digestive System Disease; Inflammatory Bowel Diseases

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: NONE

Study Groups

Fasting

All examinations are in a fasting state.

Group Type: OTHER

Multispectral optoacoustic tomography (MSOT)

Intervention Type: DIAGNOSTIC_TEST

MSOT Acuity Echo, iThera medical, Munich

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.

Group Type: OTHER

Multispectral optoacoustic tomography (MSOT)

Intervention Type: DIAGNOSTIC_TEST

MSOT Acuity Echo, iThera medical, Munich

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.

Group Type: OTHER

Multispectral optoacoustic tomography (MSOT)

Intervention Type: DIAGNOSTIC_TEST

MSOT Acuity Echo, iThera medical, Munich

Interventions

Multispectral optoacoustic tomography (MSOT)

MSOT Acuity Echo, iThera medical, Munich

Intervention Type: DIAGNOSTIC_TEST

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

University of Erlangen-Nürnberg Medical School

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

University Hospital Erlangen

Erlangen, Bavaria, Germany

Countries

Germany

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Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

346_21 B

Identifier Type: -

Identifier Source: org_study_id