Cirrhosis, LiverNCT04867954
Development of 4D Flow MRI for Risk Stratification of Variceal Bleeding in Cirrhosis
An observational study of Cirrhosis, Liver and Gastroesophageal Varices, run by University of Wisconsin, Madison at 1 site in United States.
Trial summary
The goal of this research is to validate novel non-invasive Magnetic resonance imaging (MRI) biomarkers to detect Gastroesophageal varices (GEV) in patients with cirrhosis, including fractional flow change in the portal vein and elevated azygos flow. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Cirrhosis, Liver, Gastroesophageal Varices, Fontan Procedure
- What is being tested?
- Ensure Plus®, Pre-clinical validation contrast enhanced MRI and Clinical validation MRI
- Type of treatment
- Injection or infusion
- How many people
- 84 participants
- Where
- 1 siteUnited States
- Study dates
- 28 Oct 2021to 26 Jun 2026
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: For pre-clinical validation (Aim 1), a total of 21 participants will be recruited: 7 healthy volunteers, 14 patients with GEV. For clinical validation (Aim 2-4), 100 patients will be recruited from the UWHC endoscopy clinics. For Aim 5, 5 participants will be recruited from from the UWHC endoscopy clinics.
Who may be able to join
- Healthy volunteers: Adults (>18 years) with no known liver pathology
- Obese volunteers: Adults (>18 years), no known liver pathology, body mass index (BMI) ≥ 35
- Patients: Adults (>18 years) with known cirrhosis and known Gastroesophageal varices
- Adults (>18 years) with known cirrhosis
- Adults (>18 years) with Fontan repair and diagnosed FALD
Who cannot join
- contraindications to MRI
- hypersensitivity reactions to both contrast agents
- patients with recent treatment for varices with embolization, TIPS, or other endovascular treatment
- patients with active GEV bleeding; known occlusive thrombus in portal vein, splenic vein, or superior mesenteric vein.
- patients with large HCC with known PC involvement.
- Contraindications to MRI
Show all 23Show fewer
- Recent treatment (< 1 year) for varices
- Known occlusive thrombus in portal vein; splenic vein, or superior mesenteric vein
- Large hepatocellular carcinoma (HCC) with known PV involvement
- Hypersensitivity reactions to both contrast agents
- Participants requiring conscious sedation for imaging are not eligible; participants requiring mild, oral anxiolytics for the clinical MRI scan will be allowed to participate as long as the following criteria are met:
- The participant has their own prescription for the medication
- The informed consent process is conducted prior to the self-administration of the medication.
- The participant comes to the research visit with a driver.
- Contraindications to MRI
- Recent treatment (< 1 year) for varices
- Known occlusive thrombus in portal vein; splenic vein, or superior mesenteric vein
- Large hepatocellular carcinoma (HCC) with known PV involvement
- Hypersensitivity reactions to both contrast agents
- Participants requiring conscious sedation for imaging are not eligible; participants requiring mild, oral anxiolytics for the clinical MRI scan will be allowed to participate as long as the following criteria are met:
- The participant has their own prescription for the medication
- The informed consent process is conducted prior to the self-administration of the medication.
- The participant comes to the research visit with a driver.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Wisconsin, Madison
Madison, Wisconsin, 53704
About this study
The goal of this research is to validate novel non-invasive Magnetic resonance imaging (MRI) biomarkers to detect Gastroesophageal varices (GEV) in patients with cirrhosis, including fractional flow change in the portal vein and elevated azygos flow.
End-stage liver disease (cirrhosis) is characterized by advanced fibrosis, liver failure, and portal hypertension. There are many causes of cirrhosis, including viral hepatitis, alcohol abuse, and perhaps most importantly, non-alcoholic fatty liver disease (NAFLD) and its aggressive subset, non-alcoholic steatohepatitis (NASH). 3 million new cases of end-stage liver disease (cirrhosis) are expected over the next decade. In cirrhosis, portosystemic collaterals that shunt blood away from the liver develop due to increased portal pressure. Gastroesophageal varices (GEV) are the most clinically relevant because they can cause fatal internal bleeding. GEV bleeding carries ~20% mortality at 6 weeks, and ~34% overall mortality. Identification of at-risk varices, prior to bleeding, is of paramount importance to initiate primary prophylaxis. To identify and treat at-risk patients, current guidelines recommend regular esophagogastroduodenoscopy (EGD) and variceal band ligation. Detection of high-risk GEV is key to initiating primary prophylaxis, which can reduce mortality by 50-70%.
However, endoscopy is invasive and often unnecessary when no treatment is required. Therefore, the American Association for the Study of Liver Diseases has identified the development of "non-invasive markers that predict the presence of high-risk varices" as a major unmet need.
Read the detailed description
The overall goal of this research is to implement advanced non-invasive 4D flow MRI biomarkers to predict the presence of treatable but potentially lethal GEV in patients with cirrhosis. This would facilitate the triage of patients with high-risk GEV to therapeutic EGD, while reducing unnecessary EGD procedures in patients without them.
The primary biological mechanism for development of GEV is elevated portal pressure and reversal of flow in the left gastric vein (LGV). Applying 4D flow MRI, investigators aim to detect and quantify reversed flow in the LGV to detect GEV at risk for bleeding.
Aim 1: Perform pre-clinical validations of an optimized, accelerated radial 4D flow MRI strategy, and of fat mitigation strategies for radial 4D flow MRI.
Aim 2: Determine the diagnostic performance of radial 4D flow MRI, in cirrhotic adults including
- diagnostic accuracy to identify high-risk GEV using EGD as reference standard, and
- test-retest repeatability Aim 3: Evaluate the effects and added value of a meal challenge to assess for high-risk GEV.
Aim 4: Compare the accuracy of 4D flow MRI to current non-invasive markers of liver disease.
Aim 5: Determine the feasibility of radial 4D flow MRI in participants with FALD to detect differences in mesenteric response to a meal challenge when compared to healthy controls and participants with other types of liver disease.
Research Procedures
Pre-Clinical Validation (Phase 1): A total of 21 participants (7 healthy volunteers, 14 patients with GEV) to evaluate the optimized 4D flow methods, and 20 obese subjects to evaluate fat-mitigation strategies, will be enrolled. Participants will be asked to complete a single research visit that will include a contrast enhanced MRI scan lasting up to 1 hour. Participants will be asked to fast for at least 5 hours prior to the exam. Participants will be screening a final time for contraindications to contrast enhanced MR imaging; an IV will be placed; and participants will be positioned in the MR scanner, asked to lie as still as possible and to follow some breath hold instructions.
Clinical Validation (Phase 2-3): A total of 105 patients diagnosed with cirrhosis will be enrolled. Participants will be asked to complete a single research visit, lasting approximately 2 hours, that will include the following procedures:
- Participants will be asked to fast for 12 hours prior to arriving.
- An IV will be placed for tracer administration
- Participants will undergo a research MRI lasting approximately 1.5 hours (up to 1 hour of total scan time)
- All participants will be positioned in the MRI scanner for the initial scanning session (30 min) during which the first dose of GBCA (3/4 of total dose) or the total dose of Ferumoxytol will be administered.
- 50 participants will be removed from the scanner bore, repositioned, and scanned for an additional 15 minutes (repeatability testing).
- All participants will then be removed from the scanner and asked to consume 16 ounces of Ensure Plus®. After 20 minutes, they will be repositioned in the scanner for an additional scanning session (15 min) during which, a second dose of GBCA (1/4 of total dose) will be administered if required.
- Conditions
- Cirrhosis, Liver, Gastroesophageal Varices, Fontan Procedure
- Being tested
- Ensure Plus®, Pre-clinical validation contrast enhanced MRI, Clinical validation MRI, Pre-clinical validation contrast enhanced MRI + fasting
- Medical subject headings
- Liver Cirrhosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ensure Plus®Other
In-between two MRI exams, patients will ingest a standardized meal of two cans (16oz) of Ensure Plus® (Abbott Laboratories), providing a 700cal meal (13g protein, 11g fat, 50g carbohydrates), proven to elicit a strong hyperemic splanchnic response.
Pre-clinical validation contrast enhanced MRIOther
Also called MRI
Participants will be asked to complete a single research visit that will include a contrast enhanced MRI scan lasting up to 1 hour. Participants will be asked to fast for at least 5 hours prior to the exam. Participants will be screened a final time for contraindications to contrast enhanced MR imaging; an IV will be placed; and participants will be positioned in the MR scanner, asked to lie as still as possible and to follow some breath hold instructions.
Clinical validation MRIOther
Also called MRI
Participants will be screened for any previous reactions to Ferumoxytol or GBCAs and dosing will be consistent with standard of care.
Participants will then undergo a research MRI lasting approximately 1.5 hours.
- All participants will be positioned in the MRI scanner for the initial scanning session (30 min) during which a 1/2 or 3/4 of the full dose of gadolinium based contrast agent (GBCA) or the total dose of Ferumoxytol will be administered.
- The first 50 participants will be removed from the scanner bore, repositioned, and scanned for an additional 15 minutes (repeatability testing).
- All participants will then be removed from the scanner and asked to consume 16 ounces of Ensure Plus®. After 20 minutes, they will be repositioned in the scanner for an additional scanning session (15 minutes) during which, the remaining 1/4 or 1/2 dose of GBCA will be administered, if required.
Pre-clinical validation contrast enhanced MRI + fastingOther
Also called MRI
Participants will be asked to complete a single research visit that will include a contrast enhanced MRI scan lasting up to 1.5 hours. Participants will be asked to fast for at least 5 hours prior to the exam. Participants will be screened a final time for contraindications to contrast enhanced MR imaging; an IV will be placed; and participants will be positioned in the MR scanner, asked to lie as still as possible and to follow some breath hold instructions.
| Study group | Role | What they receive |
|---|---|---|
| Healthy volunteers | 7 healthy participants will be recruited. Receives: Other: Pre-clinical validation contrast enhanced MRI | |
| Patients with small, low-risk GEV | Patients with small, low-risk Gastroesophageal varices (GEV) will be recruited. Receives: Other: Pre-clinical validation contrast enhanced MRI | |
| Patients with large, high-risk GEV | Patients with large, high-risk Gastroesophageal varices (GEV) will be recruited. Receives: Other: Pre-clinical validation contrast enhanced MRI | |
| Patients scheduled for screening or surveillance esophagogastroduodenoscopy (EGD) | 100 patients diagnosed with cirrhosis and scheduled for screening or surveillance esophagogastroduodenoscopy (EGD) procedure will be recruited. Participants will complete a single research visit, lasting approximately 2 hours, that will include the following procedures:
* Participants will fast for 12 hours prior to arriving.
* An IV will be placed and a blood sample collected (~11 mL, if necessary).
* All participants will undergo research MRI lasting approximately 1.5 hours Receives: Other: Ensure Plus®; Other: Clinical validation MRI | |
| Obese patients | 20 obese patients will be recruited Receives: Other: Pre-clinical validation contrast enhanced MRI + fasting | |
| Participants with Fontan repair and diagnosed Fontal associated liver disease (FALD) | 5 participants with Fontan repair and diagnosed FALD will be recruited. Receives: Other: Ensure Plus®; Other: Clinical validation MRI |
What is being measured
The primary outcome is the main question the study is designed to answer.
Receiver operation characteristic (ROC) curve analysis to determine diagnostic accuracy
Receiver operation characteristic (ROC) curve analysis will be performed to determine the diagnostic accuracy of 4D flow MRI to differentiate high-risk GEV from absent or low-risk GEV. The area under the curve (AUC) will be estimated for each flow measurement with 95% confidence intervals. The primary analysis is based on fractional flow change in the portal vein.
Measured: 2 hours
Variation in postprandial flow after Meal Challenge
Variations in flow after a meal will be analyzed under(log-)linear mixed effects (LME) models.
Measured: pre and post meal (approximately 2 hours)
Repeatability of 4D flow MRI: measured by summary measures of test-retest agreement with 95% Confidence intervals(CIs).
Repeatability of all flow measurements and fractional flow changes will be measured using intra-class correlation coefficient (ICC), and the wishing-subject coefficient of variation (wCV) will be estimated as summary measures of test-retest agreement with 95% CIs.
Measured: 2 hours
Diagnostic accuracy of 4D Flow MRI to detect high-risk gastroesophageal varices (GEV) compared to esophagogastroduodenoscopy (EGD) as the reference standard
Sensitivity and specificity of fractional flow change in the portal vein (FFCPV) and azygos flow thresholds
Measured: Baseline
Secondary outcomes (9)
Aspartate aminotransferase-to-platelet ratio index (APRI)
APRI is a way for doctors to measure how healthy a patient's liver is when they have a liver disease.
APRI = [(AST/upper limit of normal)/platelet count]x100
Measured: Within 3 months
Fibrosis 4 (FIB-4) index
The Fibrosis-4 score helps to estimate the amount of scarring in the liver. FIB-4 = age (years) × AST [IU/L] / [platelet count × sqr(ALT [IU/L])]
Measured: Within 3 months
Liver and spleen stiffness measurement by 2D spin-echo MR elastography
2D spin-echo MR elastography will be acquired to assess liver and spleen stiffness, using a single or dual-paddle system to ensure adequate wave-propagation in the liver and spleen
Measured: Within 3 months
Liver proton density fat fraction (PDFF) as assessed by chemical shift encoded MRI (CSE-MRI)
Liver proton density fat fraction (PDFF) is a biomarker of hepatic steatosis. It will be measured by Chemical shift encoded MRI (CSE-MRI; IDEAL IQ, GE Healthcare),pioneered at UW-Madison. It will help characterizing the possible confounders affecting 4D flow MRI
Measured: Within 3 months
Hepatic iron level quantitation by in vivo R2* MRI method
R2* is an imaging method used in MRI. R2* = (1/T2*) where R2* is a relaxation rate measured in units of Hz ([1/sec]). R2* is commonly used to look at iron levels by measuring the relaxation times of hydrogen nuclei affected by iron. The presence of the iron results in the shortening of proton relaxation times (T2*), thus increasing R2*. R2* will be measured by Chemical shift encoded MRI (CSE-MRI; IDEAL IQ, GE Healthcare), pioneered at University of Wisconsin (UW)-Madison. It will help characterizing the possible confounders affecting 4D flow MRI
Measured: Within 3 months
Child-Turcotte-Pugh (CTP) score for prognosis of cirrhosis
The Child-Turcotte-Pugh (CTP) score is used to assess the severity of cirrhosis. Parameters included are Encephalopathy, Ascites, Bilirubin levels, Albumin levels, Prothrombin Time and International Normalized Ratio (PT/INR) . Parameters are scored on point 1-3. CTP score is obtained by adding the score for each parameter. CTP scores can be categorized into A= 5-6 points, B=7-9 points and C=10-15 points. Higher points correspond to more severe cirrhosis state.
Measured: Within 3 months
Repeatability of 4D Flow MRI measurements in cirrhotic patients
Intraclass correlation coefficient (ICC) for flow measurements
Measured: Two hours
Feasibility of radial 4D Flow MRI and meal challenge protocol in FALD patients
Completion rate and image quality scores
Measured: Two hours
Postprandial mesenteric and portal flow response in FALD vs cirrhosis and healthy controls
Absolute and fractional flow changes in portal and mesenteric vessels
Measured: pre and post meal (approximately 2 hours)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Apr 2021
- Study start28 Oct 2021
- Primary completion26 Jun 2026
- Study completion26 Jun 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cirrhosis, LiverStudies of the same condition, open and under way.
- More trials run by University of Wisconsin, MadisonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 84 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Wisconsin, Madison
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Scott Reeder, MD, PhD, Principal investigator, University of Wisconsin, Madison
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04867954
- Sponsor's protocol ID
- 2021-0220
- Other IDs
- 1R01DK125783, A539300, SMPH/RADIOLOGY/RADIOLOGY, Protocol Version 1/7/26
- Status last verified
- Jul 2026
- First submitted
- 27 Apr 2021
- Last updated
- 8 Jul 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Development of 4D Flow MRI for Risk Stratification of Variceal Bleeding in Cirrhosis
- ClinicalTrials.gov ID
- NCT04867954
- Acronym / sponsor ID
- 2021-0220
- Conditions
- Cirrhosis, Liver, Gastroesophageal Varices, Fontan Procedure
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 84 participants (actual)
- Lead sponsor
- University of Wisconsin, MadisonUniversity, hospital or other
- Collaborators
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- Study start
- 28 Oct 2021 (actual)
- Primary completion
- 26 Jun 2026 (actual)
- Study completion
- 26 Jun 2026 (actual)
- First posted
- 30 Apr 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The goal of this research is to validate novel non-invasive Magnetic resonance imaging (MRI) biomarkers to detect Gastroesophageal varices (GEV) in patients with cirrhosis, including fractional flow change in the portal vein and elevated azygos flow.
End-stage liver disease (cirrhosis) is characterized by advanced fibrosis, liver failure, and portal hypertension. There are many causes of cirrhosis, including viral hepatitis, alcohol abuse, and perhaps most importantly, non-alcoholic fatty liver disease (NAFLD) and its aggressive subset, non-alcoholic steatohepatitis (NASH). 3 million new cases of end-stage liver disease (cirrhosis) are expected over the next decade. In cirrhosis, portosystemic collaterals that shunt blood away from the liver develop due to increased portal pressure. Gastroesophageal varices (GEV) are the most clinically relevant because they can cause fatal internal bleeding. GEV bleeding carries ~20% mortality at 6 weeks, and ~34% overall mortality. Identification of at-risk varices, prior to bleeding, is of paramount importance to initiate primary prophylaxis. To identify and treat at-risk patients, current guidelines recommend regular esophagogastroduodenoscopy (EGD) and variceal band ligation. Detection of high-risk GEV is key to initiating primary prophylaxis, which can reduce mortality by 50-70%.
However, endoscopy is invasive and often unnecessary when no treatment is required. Therefore, the American Association for the Study of Liver Diseases has identified the development of "non-invasive markers that predict the presence of high-risk varices" as a major unmet need.
Detailed description
The overall goal of this research is to implement advanced non-invasive 4D flow MRI biomarkers to predict the presence of treatable but potentially lethal GEV in patients with cirrhosis. This would facilitate the triage of patients with high-risk GEV to therapeutic EGD, while reducing unnecessary EGD procedures in patients without them.
The primary biological mechanism for development of GEV is elevated portal pressure and reversal of flow in the left gastric vein (LGV). Applying 4D flow MRI, investigators aim to detect and quantify reversed flow in the LGV to detect GEV at risk for bleeding.
Aim 1: Perform pre-clinical validations of an optimized, accelerated radial 4D flow MRI strategy, and of fat mitigation strategies for radial 4D flow MRI.
Aim 2: Determine the diagnostic performance of radial 4D flow MRI, in cirrhotic adults including
- diagnostic accuracy to identify high-risk GEV using EGD as reference standard, and
- test-retest repeatability Aim 3: Evaluate the effects and added value of a meal challenge to assess for high-risk GEV.
Aim 4: Compare the accuracy of 4D flow MRI to current non-invasive markers of liver disease.
Aim 5: Determine the feasibility of radial 4D flow MRI in participants with FALD to detect differences in mesenteric response to a meal challenge when compared to healthy controls and participants with other types of liver disease.
Research Procedures
Pre-Clinical Validation (Phase 1): A total of 21 participants (7 healthy volunteers, 14 patients with GEV) to evaluate the optimized 4D flow methods, and 20 obese subjects to evaluate fat-mitigation strategies, will be enrolled. Participants will be asked to complete a single research visit that will include a contrast enhanced MRI scan lasting up to 1 hour. Participants will be asked to fast for at least 5 hours prior to the exam. Participants will be screening a final time for contraindications to contrast enhanced MR imaging; an IV will be placed; and participants will be positioned in the MR scanner, asked to lie as still as possible and to follow some breath hold instructions.
Clinical Validation (Phase 2-3): A total of 105 patients diagnosed with cirrhosis will be enrolled. Participants will be asked to complete a single research visit, lasting approximately 2 hours, that will include the following procedures:
- Participants will be asked to fast for 12 hours prior to arriving.
- An IV will be placed for tracer administration
- Participants will undergo a research MRI lasting approximately 1.5 hours (up to 1 hour of total scan time)
- All participants will be positioned in the MRI scanner for the initial scanning session (30 min) during which the first dose of GBCA (3/4 of total dose) or the total dose of Ferumoxytol will be administered.
- 50 participants will be removed from the scanner bore, repositioned, and scanned for an additional 15 minutes (repeatability testing).
- All participants will then be removed from the scanner and asked to consume 16 ounces of Ensure Plus®. After 20 minutes, they will be repositioned in the scanner for an additional scanning session (15 min) during which, a second dose of GBCA (1/4 of total dose) will be administered if required.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| Healthy volunteers | – | Other: Pre-clinical validation contrast enhanced MRI7 healthy participants will be recruited. |
| Patients with small, low-risk GEV | – | Other: Pre-clinical validation contrast enhanced MRIPatients with small, low-risk Gastroesophageal varices (GEV) will be recruited. |
| Patients with large, high-risk GEV | – | Other: Pre-clinical validation contrast enhanced MRIPatients with large, high-risk Gastroesophageal varices (GEV) will be recruited. |
| Patients scheduled for screening or surveillance esophagogastroduodenoscopy (EGD) | – | Other: Ensure Plus®, Other: Clinical validation MRI100 patients diagnosed with cirrhosis and scheduled for screening or surveillance esophagogastroduodenoscopy (EGD) procedure will be recruited. Participants will complete a single research visit, lasting approximately 2 hours, that will include the following procedures: * Participants will fast for 12 hours prior to arriving. * An IV will be placed and a blood sample collected (~11 mL, if necessary). * All participants will undergo research MRI lasting approximately 1.5 hours |
| Obese patients | – | Other: Pre-clinical validation contrast enhanced MRI + fasting20 obese patients will be recruited |
| Participants with Fontan repair and diagnosed Fontal associated liver disease (FALD) | – | Other: Ensure Plus®, Other: Clinical validation MRI5 participants with Fontan repair and diagnosed FALD will be recruited. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- For pre-clinical validation (Aim 1), a total of 21 participants will be recruited: 7 healthy volunteers, 14 patients with GEV. For clinical validation (Aim 2-4), 100 patients will be recruited from the UWHC endoscopy clinics. For Aim 5, 5 participants will be recruited from from the UWHC endoscopy clinics.
Key inclusion criteria (5 listed)
- Healthy volunteers: Adults (>18 years) with no known liver pathology
- Obese volunteers: Adults (>18 years), no known liver pathology, body mass index (BMI) ≥ 35
- Patients: Adults (>18 years) with known cirrhosis and known Gastroesophageal varices
- Adults (>18 years) with known cirrhosis
- Adults (>18 years) with Fontan repair and diagnosed FALD
Key exclusion criteria (23 listed)
- contraindications to MRI
- hypersensitivity reactions to both contrast agents
- patients with recent treatment for varices with embolization, TIPS, or other endovascular treatment
- patients with active GEV bleeding; known occlusive thrombus in portal vein, splenic vein, or superior mesenteric vein.
- patients with large HCC with known PC involvement.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Ensure Plus®In-between two MRI exams, patients will ingest a standardized meal of two cans (16oz) of Ensure Plus® (Abbott Laboratories), providing a 700cal meal (13g protein, 11g fat, 50g carbohydrates), proven to elicit a strong hyperemic splanchnic response. | Other | Participants with Fontan repair and diagnosed Fontal associated liver disease (FALD), Patients scheduled for screening or surveillance esophagogastroduodenoscopy (EGD) |
| Pre-clinical validation contrast enhanced MRIAlso: MRIParticipants will be asked to complete a single research visit that will include a contrast enhanced MRI scan lasting up to 1 hour. Participants will be asked to fast for at least 5 hours prior to the exam. Participants will be screened a final time for contraindications to contrast enhanced MR imaging; an IV will be placed; and participants will be positioned in the MR scanner, asked to lie as still as possible and to follow some breath hold instructions. | Other | Healthy volunteers, Patients with large, high-risk GEV, Patients with small, low-risk GEV |
| Clinical validation MRIAlso: MRIParticipants will be screened for any previous reactions to Ferumoxytol or GBCAs and dosing will be consistent with standard of care. Participants will then undergo a research MRI lasting approximately 1.5 hours. * All participants will be positioned in the MRI scanner for the initial scanning session (30 min) during which a 1/2 or 3/4 of the full dose of gadolinium based contrast agent (GBCA) or the total dose of Ferumoxytol will be administered. * The first 50 participants will be removed from the scanner bore, repositioned, and scanned for an additional 15 minutes (repeatability testing). * All participants will then be removed from the scanner and asked to consume 16 ounces of Ensure Plus®. After 20 minutes, they will be repositioned in the scanner for an additional scanning session (15 minutes) during which, the remaining 1/4 or 1/2 dose of GBCA will be administered, if required. | Other | Participants with Fontan repair and diagnosed Fontal associated liver disease (FALD), Patients scheduled for screening or surveillance esophagogastroduodenoscopy (EGD) |
| Pre-clinical validation contrast enhanced MRI + fastingAlso: MRIParticipants will be asked to complete a single research visit that will include a contrast enhanced MRI scan lasting up to 1.5 hours. Participants will be asked to fast for at least 5 hours prior to the exam. Participants will be screened a final time for contraindications to contrast enhanced MR imaging; an IV will be placed; and participants will be positioned in the MR scanner, asked to lie as still as possible and to follow some breath hold instructions. | Other | Obese patients |
Primary outcome
Receiver operation characteristic (ROC) curve analysis to determine diagnostic accuracy
Time frame: 2 hours
Receiver operation characteristic (ROC) curve analysis will be performed to determine the diagnostic accuracy of 4D flow MRI to differentiate high-risk GEV from absent or low-risk GEV. The area under the curve (AUC) will be estimated for each flow measurement with 95% confidence intervals. The primary analysis is based on fractional flow change in the portal vein.
Variation in postprandial flow after Meal Challenge
Time frame: pre and post meal (approximately 2 hours)
Variations in flow after a meal will be analyzed under(log-)linear mixed effects (LME) models.
Repeatability of 4D flow MRI: measured by summary measures of test-retest agreement with 95% Confidence intervals(CIs).
Time frame: 2 hours
Repeatability of all flow measurements and fractional flow changes will be measured using intra-class correlation coefficient (ICC), and the wishing-subject coefficient of variation (wCV) will be estimated as summary measures of test-retest agreement with 95% CIs.
Diagnostic accuracy of 4D Flow MRI to detect high-risk gastroesophageal varices (GEV) compared to esophagogastroduodenoscopy (EGD) as the reference standard
Time frame: Baseline
Sensitivity and specificity of fractional flow change in the portal vein (FFCPV) and azygos flow thresholds
9 secondary outcomes
Aspartate aminotransferase-to-platelet ratio index (APRI)
Time frame: Within 3 months
Fibrosis 4 (FIB-4) index
Time frame: Within 3 months
Liver and spleen stiffness measurement by 2D spin-echo MR elastography
Time frame: Within 3 months
Liver proton density fat fraction (PDFF) as assessed by chemical shift encoded MRI (CSE-MRI)
Time frame: Within 3 months
Hepatic iron level quantitation by in vivo R2* MRI method
Time frame: Within 3 months
Child-Turcotte-Pugh (CTP) score for prognosis of cirrhosis
Time frame: Within 3 months
Repeatability of 4D Flow MRI measurements in cirrhotic patients
Time frame: Two hours
Feasibility of radial 4D Flow MRI and meal challenge protocol in FALD patients
Time frame: Two hours
Postprandial mesenteric and portal flow response in FALD vs cirrhosis and healthy controls
Time frame: pre and post meal (approximately 2 hours)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Jul 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Scott Reeder, MD, PhD principal investigator
University of Wisconsin, Madison
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Cirrhosis, Liver and Gastroesophageal Varices, run by University of Wisconsin, Madison at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Receiver operation characteristic (ROC) curve analysis to determine diagnostic accuracy (time frame: 2 hours). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Jul 2026.