PET/CT Scans Using the Tracer 11C-Csar, a Bile Acid Analog, to Depict and Visualize Cholestatic Disorders in Patients with Genetic Liver Disorders and Healthy Individuals

NCT06610695 | Enrolling By Invitation DMC

• 2 other identifiers: Csar_Cholestatic and healthy1-10-72-203-23
• Study Type: observational
• Target: 22
• Locations: 1 country
• Sites: 1

Brief Summary

Purpose The primary goal is to study liver diseases with defects in bile excretion. Investigators aim to do this using a radioactive tracer that mimics human bile and can be visualized with a PET/CT scanner. This will help us understand where these defects occur and how they might be treated in the future. Background Patients with liver diseases affecting bile excretion are at risk of developing cirrhosis. When bile cannot be excreted normally, it accumulates in the liver, damaging its function. It can also build up in the skin, causing yellowing and itching. Currently, patients are monitored using blood tests that do not always reflect the severity of liver disease. There are a few medications available, but they have limited efficacy. Advanced PET/CT scanning with the radioactive tracer 11C-Csar offers a way to investigate this. 11C-Csar has been developed, tested, and approved for human use at Aarhus University Hospital and has been used in previous patient studies. The study aims to use this method to show how 11C-Csar moves through the liver and bile ducts in both healthy individuals and patients with a genetic liver disease. Investigators aim to:

• Observe how defects affect the liver handling of bile acids.
• Determine the excretion kinetics of 11C-Csar, including specific rate constants.
• Compare standard blood tests with 11C-Csar PET/CT findings to assess how well blood tests reflect actual liver damage.
• Visualize potential targets for future interventions. Study Plan The scientific study involves a single examination day at the Department of Nuclear Medicine and PET. Participants will arrive fasting in the morning. An intravenous line will be placed in both arm veins, a catheter in a wrist vessel, and a hepatic vein catheter. The hepatic vein catheter will be inserted by a trained liver specialist using local anesthesia and ultrasound guidance, confirmed by X-ray. The tracer 11C-Csar and the dye indocyanine green (ICG) will be administered through the IV lines. ICG will be infused 90 minutes before scanning, and 11C-Csar will be administered at the start of the scan. Blood samples will be taken from the liver and wrist during the scan, which lasts about 45 minutes. After the scan, the catheters will be removed, and the participant can go home shortly after. Approximately 250-300 ml of blood will be drawn, which poses no risk to the participants. The total participation time is expected to be around 4 hours. Some patients may be offered a second scan if they develop new symptoms, repeating the scan when liver blood tests normalize. Participants Patients with bile accumulation liver diseases will be informed of the study during visits to the Department of Hepatology and Gastroenterology, AUH. Healthy controls will be recruited through advertisements on webpages dedicated for the purpuse. Interested individuals will receive written information. Side Effects, Risks, and Discomfort The risk of phlebitis and bleeding from IV insertion is minimal, as these procedures are performed daily. The total radiation exposure from the PET/CT scan with 11C-Csar is 2.5 mSv. Funding The study is researcher-initiated, with no financial interests for the involved researchers. Publication of Results Both negative, positive, and inconclusive results will be published. The study results will be submitted to peer-reviewed international journals in liver disease and/or radiology and presented at national and international scientific conferences. Ethics The study will be conducted following the principles of the Helsinki Declaration II with amendments and after approval by the Regional Ethics Committee for Midtjylland. While there is no immediate benefit for patients, the results will enhance our understanding of liver disease with bile acid accumulation. Investigators believe the risks and potential side effects are outweighed by the expected benefits.

Conditions

Cholestasis; Genetic Liver Disorder

Keywords

cholestasis

Outcome Measures

Primary Outcomes (1)

• The aim of this study is to apply the 11C-CSAR PET/CT method to quantify hepatobiliary secretion kinetics of 11C-Csar in both healthy human participants and patients with various cholestatic disorders, including those of genetic origin.

  Changes in the hepatobiliary excretion kinetics of 11C-CSar between patients and healthy

  through study completion, an average of 2 years

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Study subjects We plan to include eight healthy individuals and 14 patients with different cholestatic disorders. We aim to include patients with different genetic disorders affecting the hepatobiliary transport of bile acids. This includes, but is not limited to, patients with progressive familial intrahepatic cholestasis (PFIC), including protein-truncating mutations in tight-junction protein 2 gene (TJP2) and mutations in bile salt export pump (BSEP). The healthy individuals will be recruited through internet advertisements on the Facebook group "Forsøgspersoner Aarhus Universitet" and the webpages forsøgspersoner.dk, forskning.nu. Interested healthy individuals will be encouraged to contact the primary investigator, Maja. A meeting will be arranged to give oral information on the project in the same way as mentioned in the previous section. Routine blood samples will be drawn to ensure no liver disease is present. The 11C-CSAR PET/CT scan is booked when a signed consent is made.

You may qualify if:

• No prior or current history of liver diseases
• No medication that interferes with the hepatobiliary system
• Age above 18
• A signed consent must be present on the day of the 11-CSAR PET/CT scan.
• A negative pregnancy test performed on the day of the scan.

You may not qualify if:

• Prior cholecystectomy
• Pregnancy
• Claustrophobia or the inability to remain still during a 45-minute scan.
• Ultrasound sonography which ruled out mechanical obstruction.
• Age above 18
• A signed consent must be present on the day of the 11C-CSAR PET/CT scan.
• Pregnancy
• Claustrophobia or the inability to remain still during a 45-minute scan.
• Coagulation deficiency that does not allow hepatic vein catheter (relative).

Sponsors & Collaborators

• University of Aarhus: lead

Study Sites (1)

The Department of Hepatology and Gastroeneterology Aarhus University Hospital.

Aarhus, 8200, Denmark

Location

Biospecimen

Retention: SAMPLES WITHOUT DNA

Bloodsamples for a biobank.

MeSH Terms

Conditions

Cholestasis

Condition Hierarchy (Ancestors)

Bile Duct Diseases; Biliary Tract Diseases; Digestive System Diseases

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: OTHER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 30, 2024
• First Posted: September 24, 2024
• Study Start: August 15, 2024
• Primary Completion (Estimated): April 1, 2029
• Study Completion (Estimated): April 1, 2029
• Last Updated: September 24, 2024

Record last verified: 2024-08

Locations

DK (1)