Liver CirrhosisB-SMaRTNCT03114813
Can MRI Evaluate Beta-blocker Response in Portal Hypertension?
An observational study of Liver Cirrhosis and Portal Hypertension, run by University of Nottingham at 2 sites in United Kingdom.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Liver Cirrhosis, Portal Hypertension, Varix, Esophageal
- What is being tested?
- Carvedilol, MRI scan and Hepatic Venous Pressure Gradient (HVPG)
- Type of treatment
- Surgery or procedure
- How many people
- 68 participants
- Where
- 2 sitesUnited Kingdom
- Study dates
- Jan 2017to Jan 2024
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: All patients with HPVG
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
2 sites in 1 country.
United Kingdom2 sites, 2 recruiting
- Recruiting
NIHR Nottingham Biomedical Research Centre
Nottingham, Nottinghamshire, NG7 2UH
Andrea Bennett, +44 115 9249924 ext. 70611, andrea.bennett@nuh.nhs.uk
Shellie Radford, +44 115 9249924 ext. 70614, shellie.radford@nuh.nhs.uk
- Recruiting
University of Nottingham
Nottingham, NG7 2NR
Angela Shone, 01158467906, sponsor@nottingham.ac.uk
About this study
Official title: 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.
Read more
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;
- 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.
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
- Being tested
- Carvedilol, MRI scan, Hepatic Venous Pressure Gradient (HVPG)
- Medical subject headings
- Liver Cirrhosis, Hypertension, Portal, Esophageal and Gastric Varices
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CarvedilolDrug
Non-selective beta-blocker as per routine clinical care
MRI scanOther
One hour non-invasive MRI scan
Hepatic Venous Pressure Gradient (HVPG)Procedure or surgery
Second HVPG to evaluate treatment response
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: Drug: Carvedilol; Other: MRI scan; Procedure: Hepatic Venous Pressure Gradient (HVPG) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Within 12 weeks of starting treatment with beta-blockers
Secondary outcomes (2)
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)
Measured: At study visit 1
Characterise the correlation between MR elastography measures of liver stiffness at 3 Tesla with T1 relaxation time based structural changes
Measured: At study visit 1
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Apr 2017
- Study startJan 2017
- Primary completionJul 2019 (estimated)
- Study completionJan 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Liver CirrhosisStudies of the same condition, open and under way.
- More trials run by University of NottinghamThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 68 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Nottingham
- Sponsor type
- University, hospital or other
- Collaborators
- University Hospitals of Derby and Burton NHS Foundation Trust, Nottingham University Hospitals NHS Trust, University Hospital Birmingham NHS Foundation Trust
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03114813
- Sponsor's protocol ID
- 16049
- Acronym
- B-SMaRT
- Status last verified
- Apr 2018
- First submitted
- 13 Jan 2017
- Last updated
- 8 May 2018
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 May 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Beta-blocker Stratification Using Quantitative MRI Techniques to Assess Portal Pressure and Response to Treatment in Patients With Portal Hypertension
- ClinicalTrials.gov ID
- NCT03114813
- Acronym / sponsor ID
- B-SMaRT / 16049
- Conditions
- Liver Cirrhosis, Portal Hypertension, Varix, Esophageal
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 68 participants (estimated)
- Lead sponsor
- University of NottinghamUniversity, hospital or other
- Collaborators
- University Hospitals of Derby and Burton NHS Foundation Trust, Nottingham University Hospitals NHS Trust, University Hospital Birmingham NHS Foundation Trust
- Study start
- Jan 2017
- Primary completion
- Jul 2019 (estimated)
- Study completion
- Jan 2024 (estimated)
- First posted
- 14 Apr 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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;
- 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.
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 design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Clinically indicated primary prophylaxis | – | Drug: Carvedilol, Other: MRI scan, Procedure: Hepatic Venous Pressure Gradient (HVPG)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 |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- All patients with HPVG
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (7 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CarvedilolNon-selective beta-blocker as per routine clinical care | Drug | Clinically indicated primary prophylaxis |
| MRI scanOne hour non-invasive MRI scan | Other | Clinically indicated primary prophylaxis |
| Hepatic Venous Pressure Gradient (HVPG)Second HVPG to evaluate treatment response | Procedure or surgery | Clinically indicated primary prophylaxis |
Primary outcome
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
2 secondary outcomes
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
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 May 2018.
- NIHR Nottingham Digestive Diseases Biomedical Research Unit websiteLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
NIHR Nottingham Biomedical Research Centre
Nottingham, United Kingdom
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Liver Cirrhosis and Portal Hypertension, run by University of Nottingham at 2 sites in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 8 May 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 May 2018.