This site became the new ClinicalTrials.gov on June 19th. Learn more.
Show more
ClinicalTrials.gov Menu IMPORTANT: Listing of a study on this site does not reflect endorsement by the National Institutes of Health. Talk with a trusted healthcare professional before volunteering for a study. Read more...
ClinicalTrials.gov Menu IMPORTANT: Talk with a trusted healthcare professional before volunteering for a study. Read more...
ClinicalTrials.gov Menu
Give us feedback
Trial record 157 of 362 for:    hepatitis b | Recruiting, Not yet recruiting, Available Studies

Dynamic Liver Tests in Liver Disease

This study is not yet open for participant recruitment.
See Contacts and Locations
Verified August 2016 by Queen Mary University of London
Sponsor:
Collaborator:
LAPresearch UK
Information provided by (Responsible Party):
Queen Mary University of London
ClinicalTrials.gov Identifier:
NCT02782247
First received: May 6, 2016
Last updated: August 5, 2016
Last verified: August 2016
  Purpose

Chronic viral hepatitis often leads to liver scarring - cirrhosis. If the virus is eradicated from the liver, the liver scarring and liver function often recovers. In some patients the damage is too severe and recovery does not take place. It is not yet known which patients have liver disease that is too advanced to benefit from therapy nor is it known how fast the recovery occurs.

Non-intrusive dynamic liver testing (DLT) may allow us to predict the functionality of the liver post treatment and may guide us in treatment choices - for example patients who are predicted not to recover may be prioritised for transplantation. Indocyanine green (ICG) is a dye solely excreted by the liver into bile and used to measure its dynamic function. Transient elastography is similar to ultrasound and measures the degree of fibrosis within the liver.

The investigators hypothesise that the use of non-intrusive dynamic liver testing pre-treatment, will allow us to delineate patients before therapy who will have functional liver recovery following viral eradication.

The investigators hypothesise that monitoring changes in liver fibrosis and liver function in patients with historical viral clearance will allow an assessment of the likely speed of recovery of liver fibrosis and function - for example if all patients 5 years after treatment for viral hepatitis induced cirrhosis have 'normal' fibrosis and liver function scores the investigators will be able to conclude that recovery is complete within 5 years.

The investigators will perform a study pre and post-treatment assessing liver function using non-intrusive dynamic liver testing in addition to currently-used 'liver function' scoring systems, in a multivariate analysis, to determine whether or not the investigators can identify patients who are will have functional liver recovery post therapy.


Condition Intervention
Hepatitis B Hepatitis C Device: Transient elastography Device: Indocyanine Green excretion

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Diagnostic
Official Title: Changes in Dynamic Liver Function Tests in Patients With Chronic Viral Hepatitis Undergoing Antiviral Therapy

Resource links provided by NLM:


Further study details as provided by Queen Mary University of London:

Primary Outcome Measures:
  • Change from baseline following 1 year of treatment for chronic viral hepatitis with cirrhosis using transient elastography. [ Time Frame: Baseline, 4 months and 1 year ]
    Patients are treated for hepatitis B or hepatitis C and tested at baseline, 4 months and 1 year. Scores range from 0 to 75kPa with cirrhosis defined as above 11.5kPa. Change in baseline is noted. (Change = 4 month or 1 year measurement - baseline).

  • Change from baseline following 1 year of treatment for chronic viral hepatitis with cirrhosis using indocyanine green excretion test using plasma disappearance rate. [ Time Frame: Baseline, 4 months and 1 year ]
    Patients are treated for hepatitis B or hepatitis C and tested at baseline, 4 months and 1 year. Measurement of plasma disappearance rate of Indocyanine green (PDRicg) is measured with normal between 18-25%/min. Change in baseline is noted.

  • Change from baseline following 1 year of treatment for chronic viral hepatitis with cirrhosis using indocyanine green excretion test using plasma retention rate at 15 minutes. [ Time Frame: Baseline, 4 months and 1 year ]
    Patients are treated for hepatitis B or hepatitis C and tested at baseline, 4 months and 1 year. Measurement of retention rate of indocyanine green at 15 minutes is measured (ICG15) with normal being below 10%. Change in baseline is noted.


Secondary Outcome Measures:
  • Percentage of participants achieving normal fibroscan and or indocyanine green excretion test results at 3 or 5 years post initiation of treatment for viral hepatitis. [ Time Frame: 3 years, 5 years ]
    Patients treated for hepatitis B or hepatitis C with cirrhosis are tested at either 3 or 5 years after initiation of treatment. Fibroscan, score (range from 0 to 75kPa with cirrhosis defined as above 11.5kPa), measurement of plasma disappearance rate of Indocyanine green (PDRicg) (normal between 18-25%/min) and measurement of retention rate of indocyanine green at 15 minutes is measured (ICG15) (normal below 10%) are tested with the percentage of patients achieving normal in all tests reported.


Estimated Enrollment: 180
Study Start Date: May 2016
Estimated Study Completion Date: November 2017
Estimated Primary Completion Date: November 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Short term Hepatitis C patients
60 patients with chronic hepatitis C infection and cirrhosis who are planning to start antiviral therapy will be enrolled. Patients will be tested within 3 months prior to starting treatment. This will be repeated at 16 weeks (+/- 1 week) and again 1 calendar year after treatment initiation. Patients will have transient elastography and Indocyanine green excretion tests at each appointment.
Device: Transient elastography

Transient elastography will be measured using a Fibroscan® machine which is manufactured by echosens®. It has a CE mark of 0459.

It is a non-invasive method to accurately measure stiffness of a patient's liver without the need for a liver biopsy. This is measured by an externally placed ultrasound probe which creates an elastic shear wave at 50Hz, and measures the velocity of the echo through the liver tissue. The liver stiffness is measured in kilopascals (kPa). It has been shown to be 99% effective in detecting cirrhosis in hepatitis C and has been shown to correlate with hepatoma production in both hepatitis C and hepatitis B. Values range from - normal < 9.6 kPa, significant fibrosis 9.6-11.4kPa, cirrhosis >11.5kPa. It cannot be used in patients with ascites.

Other Name: Fibroscan
Device: Indocyanine Green excretion
The machine to monitor the elimination of Indocyanine green is manufactured by PULSION medical systems (Munich, Germany) and consists of the PulsioFlex monitor and LiMON module. The LiMON module is a finger probe which measure near-infrared wavelengths between 805nm and 905nm. The absorption maximum for Indocyanine green is 800nm and emission at 830nm. This is then used to produce two calculations. The first is plasma disappearance rate of indocyanine green (PDRICG). This is based on working out the constant and backward extrapolation and expressed as a percentage per minute. The other is the retention ratio after 15 minutes (ICG15).
Other Name: Pulsion Limon system
Medium term Hepatitis C patients
60 patients with chronic hepatitis C infection and cirrhosis who have been successfully treated in the past 3 or 5 years (+/- 3 months). Patients will have transient elastography and Indocyanine green excretion tests at each appointment.
Device: Transient elastography

Transient elastography will be measured using a Fibroscan® machine which is manufactured by echosens®. It has a CE mark of 0459.

It is a non-invasive method to accurately measure stiffness of a patient's liver without the need for a liver biopsy. This is measured by an externally placed ultrasound probe which creates an elastic shear wave at 50Hz, and measures the velocity of the echo through the liver tissue. The liver stiffness is measured in kilopascals (kPa). It has been shown to be 99% effective in detecting cirrhosis in hepatitis C and has been shown to correlate with hepatoma production in both hepatitis C and hepatitis B. Values range from - normal < 9.6 kPa, significant fibrosis 9.6-11.4kPa, cirrhosis >11.5kPa. It cannot be used in patients with ascites.

Other Name: Fibroscan
Device: Indocyanine Green excretion
The machine to monitor the elimination of Indocyanine green is manufactured by PULSION medical systems (Munich, Germany) and consists of the PulsioFlex monitor and LiMON module. The LiMON module is a finger probe which measure near-infrared wavelengths between 805nm and 905nm. The absorption maximum for Indocyanine green is 800nm and emission at 830nm. This is then used to produce two calculations. The first is plasma disappearance rate of indocyanine green (PDRICG). This is based on working out the constant and backward extrapolation and expressed as a percentage per minute. The other is the retention ratio after 15 minutes (ICG15).
Other Name: Pulsion Limon system
Hepatitis B Patients
60 patients with chronic hepatitis B and cirrhosis will be tested within 3 months prior to starting treatment. This will be repeated at 16 weeks (+/- 1 week) and again 1 calendar year after treatment initiation. Patients who have started treatment past 3 or 5 years (+/- 3 months) will also be tested. Patients will have transient elastography and Indocyanine green excretion tests at each appointment.
Device: Transient elastography

Transient elastography will be measured using a Fibroscan® machine which is manufactured by echosens®. It has a CE mark of 0459.

It is a non-invasive method to accurately measure stiffness of a patient's liver without the need for a liver biopsy. This is measured by an externally placed ultrasound probe which creates an elastic shear wave at 50Hz, and measures the velocity of the echo through the liver tissue. The liver stiffness is measured in kilopascals (kPa). It has been shown to be 99% effective in detecting cirrhosis in hepatitis C and has been shown to correlate with hepatoma production in both hepatitis C and hepatitis B. Values range from - normal < 9.6 kPa, significant fibrosis 9.6-11.4kPa, cirrhosis >11.5kPa. It cannot be used in patients with ascites.

Other Name: Fibroscan
Device: Indocyanine Green excretion
The machine to monitor the elimination of Indocyanine green is manufactured by PULSION medical systems (Munich, Germany) and consists of the PulsioFlex monitor and LiMON module. The LiMON module is a finger probe which measure near-infrared wavelengths between 805nm and 905nm. The absorption maximum for Indocyanine green is 800nm and emission at 830nm. This is then used to produce two calculations. The first is plasma disappearance rate of indocyanine green (PDRICG). This is based on working out the constant and backward extrapolation and expressed as a percentage per minute. The other is the retention ratio after 15 minutes (ICG15).
Other Name: Pulsion Limon system

Detailed Description:

Multiple diseases affect the liver's performance, including hepatitis' B and C viruses. Hepatitis infects the liver; ultimately leading to cirrhosis associated with complications (e.g. bleeding and death), termed decompensated cirrhosis. Hepatitis induced decompensated liver disease is likely to improve upon eradication of the virus as will liver function.

Recently, Hepatitis C has seen new, more efficacious therapies, allowing functional outcomes to be evaluated following viral clearance. It has been shown this treatment regime is effective in eliminating the virus in 70% of patients but functional improvement to be 40% with the rest stagnating or becoming worse. These patients may have benefited from liver transplantation initially, followed by viral eradication therapy.

Treatment of the Hepatitis B virus is to stop more copies to be produced within cells. This on the most part is successful and the liver recovers. However, after 5 years of treatment 26% of people do not recover sufficiently and the ability to identify these early is important to their future management.

Non-intrusive dynamic liver testing (DLT) may allow us to predict the functionality of the liver post treatment and may guide us in adequate management strategies. Indocyanine green (ICG) is a dye solely excreted by the liver into bile and used to measure its dynamic function. Transient elastography is similar to ultrasound and measures the degree of fibrosis within the liver.

The investigators hypothesise the use of non-intrusive dynamic liver testing pre-treatment, will allow us to delineate patients early, who would benefit from the most intensive treatments (e.g. transplant), and spare those with less severe disease the risks and potential side effects.

The investigators will perform a study pre and post-treatment for DLT. These will be amalgamated with currently-used scoring systems, in a multivariate analysis, to ascertain the values and thus best-treatment option for patients.

  Eligibility

Ages Eligible for Study:   18 Years to 100 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients attending The Royal London Hospital with cirrhosis (defined as fibroscan score >11.5 OR aspartate aminotransferase (AST) to platelet ratio index (APRI) score >2 OR liver biopsy or imaging report of cirrhosis) who are planning to commence antiviral therapy for either chronic hepatitis B or chronic hepatitis C.
  • Patients attending The Royal London Hospital with cirrhosis (defined as above) due to chronic hepatitis C infection who have undergone successful antiviral therapy in the past.
  • Patients attending The Royal London Hospital with cirrhosis (defined as above) due to chronic hepatitis B infection who are taking antiviral medication
  • Age 18 or above
  • Willing and able to provide Informed consent

Exclusion Criteria:

  • Any inclusion criteria not met
  • Pregnancy or breast feeding
  • Known allergy to ICG
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02782247

Contacts
Contact: Graham Foster, PhD, MBBS 02078827241 g.r.foster@qmul.ac.uk
Contact: Ali Jibran Mecci, MBBS 02078822395 a.j.mecci@qmul.ac.uk

Sponsors and Collaborators
Queen Mary University of London
LAPresearch UK
Investigators
Principal Investigator: Graham Foster, PhD, MBBS Queen Mary University of London
  More Information

Publications:

Responsible Party: Queen Mary University of London
ClinicalTrials.gov Identifier: NCT02782247     History of Changes
Other Study ID Numbers: 011006
Study First Received: May 6, 2016
Last Updated: August 5, 2016
Individual Participant Data  
Plan to Share IPD: No

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis C
Hepatitis B
Hepatitis, Viral, Human
Liver Diseases
Digestive System Diseases
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Flaviviridae Infections
Hepadnaviridae Infections
DNA Virus Infections

ClinicalTrials.gov processed this record on June 28, 2017