Multispectral Optoacoustic Tomography in Patients With Cystic Fibrosis

Multispectral Optoacoustic Tomography for the Assessment of Liver Fibrosis and Gastrointestinal Transit in Patients With Cystic Fibrosis

Cystic fibrosis (CF) is the most common hereditary disease in Central Europe. The disease is caused by a mutation in the cystic fibrosis transmembrane conductance regulator gene (CFTR). In the liver, fibrotic remodeling can lead to liver cirrhosis in the long term. Early detection of CF hepatopathy is essential to therapeutically slow down the progression of fibrotic remodeling mechanisms. Newborns suffering from CF have a significantly increased risk for the occurrence of meconium ileus and also with advancing age there are symptoms ranging from chronic constipation to Distal Intestinal Obstruction Syndrome (DIOS), due to a reduction of intestinal motility.

In this study, the degree of liver fibrosis will now be investigated in adult patients with cystic fibrosis using Multispectral Optoacoustic Imaging (MSOT). In addition, gastrointestinal passage will be studied non-invasively to investigate another affection of the gastrointestinal system.

Study Overview

• Status: Recruiting
• Conditions: Cystic Fibrosis; Liver Fibrosis; Gastrointestinal Transport Disorder; Dios
• Intervention / Treatment: Diagnostic test: Acoustic Radiation Forced Impulse Imaging; Diagnostic test: Multispectral Optoacoustic Tomography

Detailed Description

Cystic fibrosis (CF) is the most common hereditary disease in Central Europe, with an incidence of approximately 3,300 to 4,800 new cases. The disease follows an autosomal recessive pattern of inheritance, the cause being a mutation in the cystic fibrosis transmembrane conductance regulator gene (CFTR). In the liver, fibrotic remodeling can lead to liver cirrhosis in the long term. Early detection of CF hepatopathy is essential to therapeutically slow down the progression of fibrotic remodeling mechanisms. Over the past decade, measurements of liver stiffness using Acoustic Radiation Force Impulse Imaging (ARFI) have proven to be a valid tool for measuring fibrotic tissue remodeling in CF in adults and children. Furthermore, in the gastrointestinal tract, serious consequences result from the absence of the CFTR channel. Newborns suffering from CF have a significantly increased risk for the occurrence of meconium ileus and also with advancing age there are symptoms ranging from chronic constipation to DIOS (Distal Intestinal Obstruction Syndrome), due to a reduction of intestinal motility.

By means of new imaging methods, such as multispectral optoacoustic tomography, it is possible to examine not only the body's own substances but also substances foreign to the body. With Multispectral Optoacoustic Imaging (MSOT), similar to conventional sonography, a transducer is placed on the skin and instead of sound, energy is applied to the tissue by means of light flashes. This leads to a constant alternation of minimal expansions and contractions (thermoelastic expansion) of individual tissue components or molecules. Previous studies have shown that quantitative determination of hemoglobin can provide information on blood flow and inflammatory activity in the intestines of adult patients with Crohn's disease. Also, fibrotic changes in the liver can probably be detected with this method, similar to that in muscle tissue. Furthermore, we have recently shown that orally ingested Indocyanine green (ICG) can be detected in the small intestine and thus conclusions can be drawn about gastrointestinal passage, without the use of ionizing radiation. In this study, the degree of liver fibrosis will now be investigated in adult patients with cystic fibrosis using MSOT. In addition, gastrointestinal passage will be studied non-invasively to investigate another affection of the gastrointestinal system.

• Study Type: Observational
• Enrollment (Estimated): 30

Contacts and Locations

• Study Contact: Name: Alexander Schnell; Phone Number: +4991318533118; Email: alexander.schnell@uk-erlangen.de
• Study Contact Backup: Name: Adrian P Regensburger; Phone Number: +4991318533118; Email: adrian.regensburger@uk-erlangen.de

Study Locations

• Germany
  • Bavaria
    • Erlangen, Bavaria, Germany, 91054
      • Recruiting
      • University Hospital Erlange, Department of Pediatrics
      • Contact: Alexander Schnell, Dr. med.; Phone Number: +4991318533118; Email: alexander.schnell@uk-erlangen.de
      • Contact: Adrian P Regensburger, PD Dr. med.; Phone Number: +4991318533118; Email: adrian.regensburger@uk-erlangen.de

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

It is planned to study a total of 10 patients each with cystic fibrosis with/without CF-related liver disease and 10 healthy volunteers.

Description

Inclusion Criteria:

Patient cohort "Cystic Fibrosis without CF-related liver disease":

• Molecular genetic confirmed diagnosis of cystic fibrosis.
• Age over 18 years
• Written informed consent

Patient cohort "Cystic Fibrosis with CF-related liver disease":

• Molecular genetic confirmed diagnosis of cystic fibrosis

• Presence of CF-related liver disease based on Colombo criteria:

  • Hepato- and/or splenomegaly
  • Persistent elevation of transaminases in the serum
  • Sonographic evidence of liver involvement
• Age over 18 years
• Written informed consent

"Volunteer Subjects":

• Age over 18 years
• Written informed consent

Exclusion Criteria:

General:

• Pregnancy
• Breastfeeding mothers
• Tattoo in the area of the examination
• Subcutaneous fat tissue over 3 cm

Patient cohort "Cystic fibrosis without CF-related liver disease":

• Taking systemic glucocorticoids or immunosuppressants as part of a permanent medication regimen.

• Presence of CF-related liver disease based on Colombo criteria:

  • Hepato- and/or splenomegaly.
  • Persistent elevation of transaminases in the serum
  • Sonographic evidence of liver involvement.
• Acute exacerbation of infection

Patient cohort "Cystic fibrosis with CF-related liver disease":

• Taking systemic glucocorticoids or immunosuppressants as part of a permanent medication regimen.
• Decompensation of CF-related liver disease
• Acute exacerbation of infection

"volunteer subjects":

• Presence of liver disease
• Use of systemic glucocorticoids or immunosuppressants in the context of permanent medication

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
CF with liver affection; CF patients with proven CF hepatopathy	Diagnostic test: Acoustic Radiation Forced Impulse Imaging; Measurement of Liver stiffness; Other Names: ARFI; Diagnostic test: Multispectral Optoacoustic Tomography; Measurement of optoacoustic spectra in liver and gastrointestinal tract; Other Names: MSOT
CF without liver affection; CF patients without proven CF hepatopathy	Diagnostic test: Acoustic Radiation Forced Impulse Imaging; Measurement of Liver stiffness; Other Names: ARFI; Diagnostic test: Multispectral Optoacoustic Tomography; Measurement of optoacoustic spectra in liver and gastrointestinal tract; Other Names: MSOT
Healthy volunteers; Healthy volunteers without liver affection	Diagnostic test: Acoustic Radiation Forced Impulse Imaging; Measurement of Liver stiffness; Other Names: ARFI; Diagnostic test: Multispectral Optoacoustic Tomography; Measurement of optoacoustic spectra in liver and gastrointestinal tract; Other Names: MSOT

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quantitative collagen signal (Liver)	in arbitrary units	Day 1
Quantitative Indocyanine Green (ICG) signal (Intestinal)	Day 1	0, 60, 90, 120, 180, 240, 300min post ICG intake

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quantitative oxy/deoxygenated hemoglobin signal (Intestinal)	in arbitrary units	0, 60, 90, 120, 180, 240, 300min post ICG intake
Quantitative single wave lengths (Intestinal)	in arbitrary units	0, 60, 90, 120, 180, 240, 300min post ICG intake
Optoacoustic spectrum (Intestinal)	in arbitrary units, normalized	0, 60, 90, 120, 180, 240, 300min post ICG intake
Quantitative oxy/deoxygenated hemoglobin signal (Liver)	in arbitrary units	Day 1
Quantitative single wave lengths (Liver)	in arbitrary units	Day 1
Optoacoustic spectrum (Liver)	in arbitrary units, normalized	Day 1
Shear wave velocity (Liver)	in m/s	Day 1
Attenuation coefficient (Liver)	in dB/cm/MHz	Day 1
Chenodeoxycholic acid (CDCA) and respective glycine and taurine conjugates	µmol/l and /g stool	Day 1
Cholic acid (CA) and respective glycine and taurine conjugates	µmol/l and /g stool	Day 1
Deoxycholic acid (DCA) and respective glycine and taurine conjugates	µmol/l and /g stool	Day 1
Lithocholic acid (LCA) and respective glycine and taurine conjugates	µmol/l and /g stool	Day 1
Ursodeoxycholic acid (UDCA) and respective glycine and taurine conjugates	µmol/l and /g stool	Day 1

Collaborators and Investigators

• Sponsor: University of Erlangen-Nürnberg Medical School
• Collaborators: Adrian Regensburger
• Investigators: Principal Investigator: Alexander Schnell, Department of Pediatric and Adolescent Medicine, University Hospital Erlangen; Principal Investigator: Adrian P Regensburger, Department of Pediatric and Adolescent Medicine, University Hospital Erlangen

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2023
• Primary Completion (Estimated): September 30, 2024
• Study Completion (Estimated): March 31, 2025

Study Registration Dates

• First Submitted: September 5, 2023
• First Submitted That Met QC Criteria: September 25, 2023
• First Posted (Actual): October 3, 2023

Study Record Updates

• Last Update Posted (Actual): October 23, 2023
• Last Update Submitted That Met QC Criteria: October 19, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: Cystic Fibrosis; MSOT; Liver Fibrosis; Gastrointestinal Transit
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Infant, Newborn, Diseases; Liver Diseases; Genetic Diseases, Inborn; Pancreatic Diseases; Fibrosis; Liver Cirrhosis; Cystic Fibrosis
• Other Study ID Numbers: CF_MSOT

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No