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Multispectral Optoacoustic Tomography in Patients With Cystic Fibrosis

Recruiting
Conditions
Cystic Fibrosis
Liver Fibrosis
Gastrointestinal Transport Disorder
Dios
Interventions
Diagnostic Test: Acoustic Radiation Forced Impulse Imaging
Diagnostic Test: Multispectral Optoacoustic Tomography
Registration Number
NCT06063785
Lead Sponsor
University of Erlangen-Nürnberg Medical School
Brief 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.

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.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
30
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 & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Arm && Interventions
GroupInterventionDescription
CF with liver affectionAcoustic Radiation Forced Impulse ImagingCF patients with proven CF hepatopathy
CF with liver affectionMultispectral Optoacoustic TomographyCF patients with proven CF hepatopathy
CF without liver affectionAcoustic Radiation Forced Impulse ImagingCF patients without proven CF hepatopathy
Healthy volunteersAcoustic Radiation Forced Impulse ImagingHealthy volunteers without liver affection
Healthy volunteersMultispectral Optoacoustic TomographyHealthy volunteers without liver affection
CF without liver affectionMultispectral Optoacoustic TomographyCF patients without proven CF hepatopathy
Primary Outcome Measures
NameTimeMethod
Quantitative collagen signal (Liver)Day 1

in arbitrary units

Quantitative Indocyanine Green (ICG) signal (Intestinal)0, 60, 90, 120, 180, 240, 300min post ICG intake

Day 1

Secondary Outcome Measures
NameTimeMethod
Deoxycholic acid (DCA) and respective glycine and taurine conjugatesDay 1

µmol/l and /g stool

Cholic acid (CA) and respective glycine and taurine conjugatesDay 1

µmol/l and /g stool

Lithocholic acid (LCA) and respective glycine and taurine conjugatesDay 1

µmol/l and /g stool

Quantitative oxy/deoxygenated hemoglobin signal (Liver)Day 1

in arbitrary units

Quantitative single wave lengths (Liver)Day 1

in arbitrary units

Optoacoustic spectrum (Intestinal)0, 60, 90, 120, 180, 240, 300min post ICG intake

in arbitrary units, normalized

Optoacoustic spectrum (Liver)Day 1

in arbitrary units, normalized

Quantitative single wave lengths (Intestinal)0, 60, 90, 120, 180, 240, 300min post ICG intake

in arbitrary units

Attenuation coefficient (Liver)Day 1

in dB/cm/MHz

Chenodeoxycholic acid (CDCA) and respective glycine and taurine conjugatesDay 1

µmol/l and /g stool

Quantitative oxy/deoxygenated hemoglobin signal (Intestinal)0, 60, 90, 120, 180, 240, 300min post ICG intake

in arbitrary units

Ursodeoxycholic acid (UDCA) and respective glycine and taurine conjugatesDay 1

µmol/l and /g stool

Shear wave velocity (Liver)Day 1

in m/s

Trial Locations

Locations (1)

University Hospital Erlange, Department of Pediatrics

🇩🇪

Erlangen, Bavaria, Germany

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