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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03114813
Recruitment Status : Recruiting
First Posted : April 14, 2017
Last Update Posted : May 8, 2018
Sponsor:
Collaborators:
University Hospitals of Derby and Burton NHS Foundation Trust
Nottingham University Hospitals NHS Trust
University Hospital Birmingham NHS Foundation Trust
Information provided by (Responsible Party):
University of Nottingham

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.


Condition or disease Intervention/treatment
Liver Cirrhosis Portal Hypertension Varix, Esophageal Drug: Carvedilol Other: MRI scan Procedure: Hepatic Venous Pressure Gradient (HVPG)

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Study Type : Observational
Estimated Enrollment : 68 participants
Observational Model: Cohort
Time Perspective: Prospective
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

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Varicose Veins
Drug Information available for: Carvedilol

Group/Cohort Intervention/treatment
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




Primary Outcome Measures :
  1. 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 ]

Secondary Outcome Measures :
  1. 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 ]
  2. 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 ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 85 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
All patients with HPVG
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03114813


Locations
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United Kingdom
NIHR Nottingham Biomedical Research Centre Recruiting
Nottingham, Nottinghamshire, United Kingdom, NG7 2UH
Contact: Andrea Bennett    +44 115 9249924 ext 70611    andrea.bennett@nuh.nhs.uk   
Contact: Shellie Radford    +44 115 9249924 ext 70614    shellie.radford@nuh.nhs.uk   
Principal Investigator: Guruprasad Aithal         
University of Nottingham Recruiting
Nottingham, United Kingdom, NG7 2NR
Contact: Angela Shone    01158467906    sponsor@nottingham.ac.uk   
Sponsors and Collaborators
University of Nottingham
University Hospitals of Derby and Burton NHS Foundation Trust
Nottingham University Hospitals NHS Trust
University Hospital Birmingham NHS Foundation Trust
Additional Information:
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Responsible Party: University of Nottingham
ClinicalTrials.gov Identifier: NCT03114813    
Other Study ID Numbers: 16049
First Posted: April 14, 2017    Key Record Dates
Last Update Posted: May 8, 2018
Last Verified: April 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Additional relevant MeSH terms:
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Liver Cirrhosis
Hypertension, Portal
Esophageal and Gastric Varices
Hypertension
Vascular Diseases
Cardiovascular Diseases
Liver Diseases
Digestive System Diseases
Esophageal Diseases
Gastrointestinal Diseases
Carvedilol
Adrenergic beta-Antagonists
Adrenergic Antagonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Antihypertensive Agents
Antioxidants
Protective Agents
Calcium Channel Blockers
Membrane Transport Modulators
Calcium-Regulating Hormones and Agents
Vasodilator Agents
Adrenergic alpha-1 Receptor Antagonists
Adrenergic alpha-Antagonists