NCT04867954

Development of 4D Flow MRI for Risk Stratification of Variceal Bleeding in Cirrhosis

• Status: Recruiting
• Phase: —
• Study type: Observational
• Enrollment: 146 (estimated)
• Sponsor: University of Wisconsin, Madison · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Accepted

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. 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 1. diagnostic accuracy to identify high-risk GEV using EGD as reference standard, and 2. 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

Interventions

Type	Name	Description
OTHER	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	Pre-clinical validation contrast enhanced 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.
OTHER	Clinical validation 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.
OTHER	Pre-clinical validation contrast enhanced MRI + fasting	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.

Timeline

• Start date: 2021-10-28
• Primary completion: 2026-06-30
• Completion: 2026-06-30
• First posted: 2021-04-30
• Last updated: 2026-04-09

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated device study