Can MRI Evaluate Beta-blocker Response in Portal Hypertension? (B-SMaRT)
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|ClinicalTrials.gov Identifier: NCT03114813|
Recruitment Status : Recruiting
First Posted : April 14, 2017
Last Update Posted : May 8, 2018
To test if MRI can detect meaningful changes in portal pressure in the liver to assess whether treatment with beta-blockers has worked.
Most people with liver disease do not have symptoms. Over time they develop 'cirrhosis' - severe liver scarring. In the United Kingdom deaths due to cirrhosis have doubled over the last decade, because of increasing rates of alcohol consumption and obesity, while heart, kidney, lung diseases, strokes and cancer fatalities have fallen.
Cirrhosis causes increased pressure within the liver and changes in the circulation leading to the development of varicose veins in the gullet and stomach called 'varices'. Varices bleed easily, leading to emergency situations that can be life threatening. However, if the increased pressure within the liver (portal pressure) is detected early, then treatment can prevent variceal bleeding. The only test we have to predict prognosis and treatment success in someone with cirrhosis is by measuring the portal pressure.
Measuring portal pressure:
Currently the only existing test to measure portal pressure is to pass a pressure sensor through a vein in the neck, down into the liver. This is called the hepatic venous pressure gradient (HVPG) measurement. The HVPG measurement is disliked by patients because it is an invasive procedure. It is also expensive and not widely available. Hence, patients with cirrhosis need to have regular camera tests (endoscopies) to look for varices.
How can you treat varices?
- With tablets to lower the pressure (beta-blockers)
- Endoscopy treatment (banding)
Both have advantages and disadvantages;
- Beta-blockers only lower the portal pressure in about half of those that take them, with some evidence they may also have a protective effect against infections from the bowel by increasing the speed of bowel motion
- Treating the varices with endoscopy requires several endoscopies and can lead to life-threatening bleeding.
Most patients are therefore given beta-blockers and monitored closely to see if they work.
Why does it matter?
Beta-blockers can cause side effects (e.g. fainting) that are unpleasant enough to make up to one third of patients stop taking them. Beta-blockers only reduce the portal pressure in half of patients. The remaining patients are exposed to potential side effects and possible harm in those with the most advanced liver disease. These patients may still have a life-threatening bleed as the varices have not been adequately treated. There is a desperate need to discover whether the portal pressure changes with treatment (such as with beta-blockers) without invasive tests across the NHS.
Researchers in Nottingham have shown MRI can be used as an accurate marker of portal pressure with just one scan. To be useful to patients, doctors and researchers, this study will investigate whether MRI can detect meaningful changes in portal pressure after treatment with beta-blockers. This study has been designed with patient and public involvement (PPI) integrated throughout. A focus group shaped the study design and committed to collaborate in developing patient materials, recruitment, retention and dissemination.
All patients who have HVPG will be given information about the study.
Study Visit 1
- One hour MRI scan
Endoscopy to identify varices
- If varices are present the patient will be started on beta-blockers and invited to visit 2
- If there are no varices, patients will return to regular follow up with the liver team
Study Visit 2 (after one week)
- Assess side effects, blood pressure and pulse
- Increase dose of beta-blocker as appropriate
Study Visit 3 (after 4-12 weeks)
- One hour MRI scan
- Repeat HVPG measurement
Treatment success is determined by the second HVPG measurement. If beta-blockers are working they will be continued. If not, the patient will have treatment with endoscopy. This represents the ideal pathway which is more personalised than current standard care.
|Condition or disease||Intervention/treatment|
|Liver Cirrhosis Portal Hypertension Varix, Esophageal||Drug: Carvedilol Other: MRI scan Procedure: Hepatic Venous Pressure Gradient (HVPG)|
|Study Type :||Observational|
|Estimated Enrollment :||68 participants|
|Official Title:||Beta-blocker Stratification Using Quantitative MRI Techniques to Assess Portal Pressure and Response to Treatment in Patients With Portal Hypertension|
|Study Start Date :||January 2017|
|Estimated Primary Completion Date :||July 2019|
|Estimated Study Completion Date :||January 2024|
Clinically indicated primary prophylaxis
Approach all those who have had a portal pressure measurement (HVPG) as part of their routine clinical care.
At baseline participants will consent to have an additional MRI scan before undergoing clinical screening Endoscopy.
All participants found to have oesophgeal varices that require primary prophylaxis, will be started on Carvedilol 6.25mg.
After 1 week, participants will return for dose optimisation
After 4-12 weeks of treatment, participants will have:
Non-selective beta-blocker as per routine clinical care
Other: MRI scan
One hour non-invasive MRI scan
Procedure: Hepatic Venous Pressure Gradient (HVPG)
Second HVPG to evaluate treatment response
- Kappa agreement between quantitative MRI estimates of HVPG (modelled by liver T1 and splenic artery velocity) and HVPG to stratify treatment response to beta-blockers in patients requiring primary prophylaxis for oesophageal varices. [ Time Frame: Within 12 weeks of starting treatment with beta-blockers ]
- Validate univariate and multivariate quantitative MRI measures (structural, haemodynamic) associated with portal pressure at a field strength of 3 Tesla (in particular previously published model with T1 and splenic artery velocity) [ Time Frame: At study visit 1 ]
- Characterise the correlation between MR elastography measures of liver stiffness at 3 Tesla with T1 relaxation time based structural changes [ Time Frame: At study visit 1 ]
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03114813
|NIHR Nottingham Biomedical Research Centre||Recruiting|
|Nottingham, Nottinghamshire, United Kingdom, NG7 2UH|
|Contact: Andrea Bennett +44 115 9249924 ext 70611 firstname.lastname@example.org|
|Contact: Shellie Radford +44 115 9249924 ext 70614 email@example.com|
|Principal Investigator: Guruprasad Aithal|
|University of Nottingham||Recruiting|
|Nottingham, United Kingdom, NG7 2NR|
|Contact: Angela Shone 01158467906 firstname.lastname@example.org|