MBT Versus HVPG in Identifying Responders to Portal Hypertension Therapy

December 19, 2022 updated by: Meridian Bioscience, Inc.

Pilot Study to Evaluate the Correlation Between ¹³C Methacetin Breath Test (MBT) and HVPG Measurement as a Tool for Identifying Responders to Portal Hypertension Therapy

The purpose of this study is to determine the effect on the (carbon 13 labelled(13C)-Methacetin Breath Test (MBT) of i.v. propranolol, a non-selective beta blocker (NSBB) following initial administration and after chronic use of each of these agents. The correlation of the MBT with Hepatic Venous Pressure Gradient (HVPG) measurement before and after treatment will be assessed. Additionally, the MBT measurements following 60 days of therapy will be compared to the first MBT measurement and to the second MBT measurement, post HVPG. Each patient's subsequent MBT measurement will be compared to his previous MBT results in order to determine his/her response to therapy.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Variceal bleeding is a life threatening complication of cirrhosis, which still carries a high mortality. Non selective beta-adrenergic blockers are effective at preventing first time variceal bleeding and re-bleeding. The efficacy of these drugs depends on the magnitude of reduction in portal pressure after administration, which varies widely between patients. Studies have shown that a reduction in portal pressure (as measured by HVPG) to 20% from baseline or to values ≤ 12 millimeters of mercury (mmHg) is associated with a low residual risk of bleeding . Patients with such a reduction are considered to be "responders" to beta blocker (BB) therapy. Unfortunately, a significant percentage of patients do not respond to therapy and need to be prescribed to an alternative therapy. The clinical application of this observation is limited since it requires a repeated HVPG measurement,which is not feasible in most cases. A non-invasive breath test that can assess portal pressure in correlation to HVPG and allow efficient management of patients at risk, could be very useful.

Study Type

Interventional

Enrollment (Actual)

19

Phase

  • Phase 1

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

  • Israel
      • Haifa, Israel, 34362
        • Carmel Medical Center

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

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

-> 18 years old (M/F)

-Diagnosis of cirrhosis: i. By liver biopsy ii. Or strong suspicion of cirrhosis by accepted criteria for the clinical diagnosis of cirrhosis (e.g. peripheral edema or varices, palpable hard left lobe of the liver, small right lobe span or palpable splenomegaly), and/or radiological evidence of cirrhosis (by abdominal US, CT, or MRI, showing a nodular liver and/or portosystemic collaterals with portal vein patency and/or ascites and/or splenomegaly, and/or colloid shift on a colloid-isotope liver-spleen scan), and/or laboratory variables (platelets <100,000/mm3, albumin< 3.5g/dL, or international normalized ratio (INR)>1.3) iii. Presence of esophageal varices (without previous variceal bleeding episode) or HVPG≥10mmHg 12mmHg from previous testing.

-Has been scheduled for hemodynamic study testing, including response to acute therapy.-

Exclusion Criteria:

  • Patients already receiving beta blockers
  • Hepatocellular carcinoma
  • Portal vein thrombosis
  • Contraindications to non-selective beta blocker Propanolol
  • Cholestatic liver disease
  • Severe heart, pulmonary or renal disease.
  • Patient has previous surgical bypass surgery for morbid obesity
  • Patient has extensive small bowel resection
  • Any major surgery in the past 3 months.
  • Patient is a recipient of any organ transplant
  • Patient allergic to acetaminophen.
  • Patients who are taking hepatotoxic drugs
  • Patient, based on the opinion of the investigator, should not be enrolled into this study.
  • Patients unable or unwilling to sign informed consent
  • Patients that are participating in other clinical trials evaluating experimental treatments or procedures or have participated in a clinical trial in the past 3 months.

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

  • Primary Purpose: Supportive Care
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Methacetin (for BT) before / after Propanolol treatment.
The methacetin breath test (MBT) will be performed before and after (within 2 hours) injection of Propanolol (BB) dose and once again after 60 days of oral administration of Propanolol.
Device: Methacetin (with Breath testing device)
The methacetin is enriched with carbon 13, a stable non- radioactive isotope, and has been found to be safe in hundreds of studies. The material is very similar to acetominophen. 75 milligrams (mm) of this material pre- dissolved in water are used. This material undergoes rapid metabolism by the liver.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Correlation between HVPG and MBT and their changes following the i.v. administration of Propranolol
Time Frame: 7 days
MBT baseline measure will be measured within a week before the anticipated HVPG procedure, but not on the same day. The HVPG will be measured approximately 30 minutes after i.v. propanolol is given and the MBT will be performed approximately one hour later.
7 days
The changes between MBT at baseline level and after chronic treatment in Propranolol
Time Frame: 7 days
MBT baseline measure will be measured within a week before the anticipated HVPG procedure, but not on the same day. The HVPG will be measured approximately 30 minutes after i.v. propanolol is given and the MBT will be performed approximately one hour later.
7 days
MBT correlation to clinical events after 2 month of treatment
Time Frame: 67 days
The MBT will be performed on subjects again after 60 days of oral beta blocker treatment and its results will be compared to previous MBT values.
67 days

Collaborators and Investigators

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

Sponsor

Meridian Bioscience, Inc.

Investigators

  • Principal Investigator: Eyal Ashkenazi, M.D., Carmel Medical Center

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.

General Publications

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 (Actual)

October 1, 2013

Primary Completion (Actual)

August 1, 2017

Study Completion (Actual)

August 1, 2017

Study Registration Dates

First Submitted

May 8, 2013

First Submitted That Met QC Criteria

May 9, 2013

First Posted (Estimate)

May 10, 2013

Study Record Updates

Last Update Posted (Actual)

December 20, 2022

Last Update Submitted That Met QC Criteria

December 19, 2022

Last Verified

December 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • HVPG-BB-EX-513

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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