Multispectral Optoacoustic Tomography in Patients With Cystic Fibrosis

Cystic Fibrosis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06063785
• Other study ID #: CF_MSOT
• Status: Recruiting
• Start date: October 1, 2023
• Est. completion date: March 31, 2025

Study information

• Verified date: October 2023
• Source: University of Erlangen-Nürnberg Medical School
• Contact: Alexander Schnell
• Phone: +4991318533118
• Email: alexander.schnell[@]uk-erlangen.de
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: March 31, 2025
• Est. primary completion date: September 30, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Cystic Fibrosis
• Fibrosis
• Liver Cirrhosis
• Liver Fibrosis

Intervention

Diagnostic Test:
• Acoustic Radiation Forced Impulse Imaging
Measurement of Liver stiffness
• Multispectral Optoacoustic Tomography
Measurement of optoacoustic spectra in liver and gastrointestinal tract

Locations

Country	Name	City	State
Germany	University Hospital Erlange, Department of Pediatrics	Erlangen	Bavaria

Sponsors (2)

Lead Sponsor	Collaborator
University of Erlangen-Nürnberg Medical School	Adrian Regensburger

Country where clinical trial is conducted

Germany, 

Outcome

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