Can MRI Evaluate Beta-blocker Response in Portal Hypertension?

NCT ID: NCT03114813

Last Updated: 2018-05-08

Basic Information

• Recruitment Status: UNKNOWN
• Total Enrollment: 68 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2017-01-31
• Study Completion Date: 2024-01-31

Brief Summary

Aim:

To test if MRI can detect meaningful changes in portal pressure in the liver to assess whether treatment with beta-blockers has worked.

Liver Disease:

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.

Portal pressure:

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?

Two options;

1. With tablets to lower the pressure (beta-blockers)

2. 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.

Proposed study:

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.

Conditions

Liver Cirrhosis; Portal Hypertension; Varix, Esophageal

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

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:

• repeat one hour MRI scan
• repeat HVPG to evaluate treatment response

Carvedilol

Intervention Type: DRUG

Non-selective beta-blocker as per routine clinical care

MRI scan

Intervention Type: OTHER

One hour non-invasive MRI scan

Hepatic Venous Pressure Gradient (HVPG)

Intervention Type: PROCEDURE

Second HVPG to evaluate treatment response

Interventions

Carvedilol

Non-selective beta-blocker as per routine clinical care

Intervention Type: DRUG

MRI scan

One hour non-invasive MRI scan

Intervention Type: OTHER

Hepatic Venous Pressure Gradient (HVPG)

Second HVPG to evaluate treatment response

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

• Patients of more than 18 and less than 85 years of age
• Patients who have had HVPG measurements within the last 12 weeks.
• Underlying portal hypertension due to chronic liver disease - alcoholic liver disease, non-alcoholic fatty liver disease (NAFLD), chronic hepatitis B or C and haemochromatosis.
• Patients investigated with a clinical suspicion of portal hypertension, but have normal portal pressures on HVPG measurements.
• Ability to consent to participate in the study.
• Patients already on NSBBs who have stopped treatment for two weeks

Exclusion Criteria

• Unable to give informed consent
• Patients with underlying diseases which are NOT related to alcohol excess, NAFLD, chronic hepatitis B, C or haemochromatosis.
• Pregnant women.
• Absolute contraindications for MRI (including participants with metal in/around the eyes)
• Absolute contraindications for NSBBs (allergy, presence of asthma)
• Patients currently on NSBBs or nitrates (can be included if withheld for two weeks)
• mean arterial pressure <55 mm Hg or pulse < 50 beats per minute at baseline

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Hospitals of Derby and Burton NHS Foundation Trust

OTHER

Sponsor Role: collaborator

Nottingham University Hospitals NHS Trust

OTHER

Sponsor Role: collaborator

University Hospital Birmingham NHS Foundation Trust

OTHER

Sponsor Role: collaborator

University of Nottingham

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

NIHR Nottingham Biomedical Research Centre

Nottingham, Nottinghamshire, United Kingdom

Site Status: RECRUITING

University of Nottingham

Nottingham, , United Kingdom

Site Status: RECRUITING

Countries

United Kingdom

Facility Contacts

Andrea Bennett

Role: primary

andrea.bennett@nuh.nhs.uk

+44 115 9249924 ext. 70611

Shellie Radford

Role: backup

shellie.radford@nuh.nhs.uk

+44 115 9249924 ext. 70614

Angela Shone

Role: primary

sponsor@nottingham.ac.uk

01158467906

Related Links

https://nddcbru.org.uk

NIHR Nottingham Digestive Diseases Biomedical Research Unit website

Other Identifiers

16049

Identifier Type: -

Identifier Source: org_study_id