Can MRI Evaluate Beta-blocker Response in Portal Hypertension? (B-SMaRT)

May 2, 2018 updated by: University of Nottingham

Beta-blocker Stratification Using Quantitative MRI Techniques to Assess Portal Pressure and Response to Treatment in Patients With Portal Hypertension

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Observational

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
68

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United Kingdom
      • Nottingham, United Kingdom, NG7 2NR
    • Nottinghamshire
      • Nottingham, Nottinghamshire, United Kingdom, NG7 2UH
        • Recruiting
        • NIHR Nottingham Biomedical Research Centre
        • Contact:
        • Contact:
        • Principal Investigator:
          • Guruprasad Aithal

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

14 years to 81 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

All patients with HPVG

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort

Group / Cohort

A group or subgroup of participants in an observational study that is assessed for biomedical or health outcomes.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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
Drug: Carvedilol
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

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
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
Within 12 weeks of starting treatment with beta-blockers

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Time Frame
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
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
At study visit 1

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University of Nottingham

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Nottingham University Hospitals NHS Trust
University Hospital Birmingham NHS Foundation Trust
University Hospitals of Derby and Burton NHS Foundation Trust

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 1, 2017

Primary Completion (Anticipated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
July 1, 2019

Study Completion (Anticipated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
January 1, 2024

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
January 13, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 10, 2017

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
April 14, 2017

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
May 8, 2018

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 2, 2018

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
April 1, 2018

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 16049

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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