Clinical trial NCT06063785: Multispectral Optoacoustic Tomography in Patients With Cystic Fibrosis
Official title: Multispectral Optoacoustic Tomography for the Assessment of Liver Fibrosis and Gastrointestinal Transit in Patients With Cystic Fibrosis
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Cystic Fibrosis
Liver Fibrosis
Gastrointestinal Transport Disorder
Dios
Keywords: Cystic Fibrosis
MSOT
Liver Fibrosis
Gastrointestinal Transit
Lead sponsor: University of Erlangen-Nürnberg Medical School
Sponsor class: OTHER
Collaborators: name: Adrian Regensburger
First posted: 2023-10-03
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Quantitative collagen signal (Liver)
timeFrame: Day 1
measure: Quantitative Indocyanine Green (ICG) signal (Intestinal)
timeFrame: 0, 60, 90, 120, 180, 240, 300min post ICG intake
Secondary outcomes:
measure: Quantitative oxy/deoxygenated hemoglobin signal (Liver)
timeFrame: Day 1
measure: Quantitative oxy/deoxygenated hemoglobin signal (Intestinal)
timeFrame: 0, 60, 90, 120, 180, 240, 300min post ICG intake
measure: Quantitative single wave lengths (Intestinal)
timeFrame: 0, 60, 90, 120, 180, 240, 300min post ICG intake
measure: Quantitative single wave lengths (Liver)
timeFrame: Day 1
measure: Optoacoustic spectrum (Intestinal)
timeFrame: 0, 60, 90, 120, 180, 240, 300min post ICG intake
measure: Optoacoustic spectrum (Liver)
timeFrame: Day 1
measure: Shear wave velocity (Liver)
timeFrame: Day 1
measure: Attenuation coefficient (Liver)
timeFrame: Day 1
measure: Chenodeoxycholic acid (CDCA) and respective glycine and taurine conjugates
timeFrame: Day 1
measure: Cholic acid (CA) and respective glycine and taurine conjugates
timeFrame: Day 1
measure: Deoxycholic acid (DCA) and respective glycine and taurine conjugates
timeFrame: Day 1
measure: Lithocholic acid (LCA) and respective glycine and taurine conjugates
timeFrame: Day 1
measure: Ursodeoxycholic acid (UDCA) and respective glycine and taurine conjugates
timeFrame: Day 1
Other outcomes:
Locations:
city: Erlangen
country: Germany
facility: University Hospital Erlange, Department of Pediatrics
state: Bavaria
Study officials:
affiliation: Department of Pediatric and Adolescent Medicine, University Hospital Erlangen
name: Alexander Schnell
role: PRINCIPAL_INVESTIGATOR
affiliation: Department of Pediatric and Adolescent Medicine, University Hospital Erlangen
name: Adrian P Regensburger
role: PRINCIPAL_INVESTIGATOR
References: