Community Liver Biomarkers Cohort

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2014 by University of Nottingham
Sponsor:
Information provided by (Responsible Party):
University of Nottingham
ClinicalTrials.gov Identifier:
NCT02037867
First received: January 14, 2014
Last updated: January 15, 2014
Last verified: January 2014
  Purpose

Deaths due to advanced liver scarring (liver cirrhosis) continue to increase, and liver disease is now the 3rd leading cause of premature death in the United Kingdom. The majority of liver disease is lifestyle related (alcohol, obesity and associated type 2 diabetes, injecting drug use) and therefore reversible if caught at a precirrhosis stage. However, current liver function blood tests are poor inadequate, and subsequently a large burden of liver disease is currently missed.

A variety of noninvasive liver biomarkers (blood and imaging tests) have been developed which identify liver disease accurately at earlier stages of scarring. The identification of liver disease in the community, where previous studies have discovered a large burden of previously unidentified but significant liver disease, is therefore a feasible place to develop new liver disease investigation pathways using these noninvasive markers.

In collaboration with the Department of Health, Nottingham University Hospitals have commenced a pilot community liver disease pathway in two General Practices in Nottingham in February 2012. Patients with liver risk factors (hazardous alcohol use, obesity or type 2 diabetes)are invited to take part in the pathway. Patients undergo a simple blood test (AST:ALT ratio and BARD score), with a high test result requiring referral for a liver stiffness scan (Fibroscan)which is performed in the community setting. High threshold scan values are reviewed by a consultant liver specialist in a community liver clinic. Preliminary findings show that the pathway accurately identifies patients with early liver scarring and previously unidentified significant liver disease. The participating General Practitioners have also noted a striking number of patients finally engaging in important lifestyle changes following pathway implementation. A second phase of the pilot pathway, in 2 Inner City General Practices with a total practice population of c.14,000 patients commenced in June 2013.

We have subsequently designed this cohort study, where pilot participants will be consented for follow up over a long period. We will assess future liver-related and cardiovascular events (including death), and perform qualitative patient interviews to assess the reasons for and persistence of lifestyle changes after liver disease investigation. We hypothesize that stratification of liver disease in the community will unearth a significant amount of previously undetected but significant chronic liver disease. Moreover, we will evaluate whether stratification of liver disease using these tests predicts future liver and cardiovascular disease and death, and whether stratification has an impact on patient's future lifestyle choices.


Condition Intervention
Chronic Liver Disease
Hazardous Alcohol Use
Type 2 Diabetes
Persistently Elevated ALT
Device: Fibrosis Biomarkers

Study Type: Observational [Patient Registry]
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration: 20 Years
Official Title: The Stratification of Liver Disease in the Community Using Fibrosis Biomarkers

Resource links provided by NLM:


Further study details as provided by University of Nottingham:

Primary Outcome Measures:
  • Liver and cardiovascular-related mortality [ Time Frame: 20 years ] [ Designated as safety issue: No ]
    Death recorded as resulting from cardiovascular or liver-related causes


Secondary Outcome Measures:
  • Liver Cirrhosis [ Time Frame: 20 years ] [ Designated as safety issue: No ]
    Incidence of compensated and decompensated cirrhosis diagnosis during the study period.

  • Cardiovascular Disease [ Time Frame: 20 years ] [ Designated as safety issue: No ]
    Incidence of cardiovascular disease events(defined as symptomatic coronary or cerebrovascular disease)during the study period.

  • All-cause mortality [ Time Frame: 20 years ] [ Designated as safety issue: No ]
    Recording of any death during the study period


Biospecimen Retention:   Samples Without DNA

Serum and urine samples stored a -80 degrees Celsius.


Estimated Enrollment: 2000
Study Start Date: May 2013
Estimated Study Completion Date: May 2033
Estimated Primary Completion Date: May 2033 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
Patients

Patients identified with one of the below chronic liver disease risk factors and undergoing community liver disease stratification using fibrosis biomarkers:

  • Hazardous alcohol use (>14 units per week in females, >21 units per week in males, alcohol AUDIT score >=8 or read code relevant to alcohol abuse on GP system)
  • Type 2 Diabetes
  • Persistently raised serum ALT level, negative liver serology, and absence of above 2 risk factors
Device: Fibrosis Biomarkers
Sequential liver disease stratification with serum biomarker and liver stiffness scan (Transient Elastography)
Other Name: AST:ALT ratio, BARD score, Transient Elastography, Fibroscan

  Hide Detailed Description

Detailed Description:

Objectives:

  1. To establish a community based cohort with risk factors for liver disease and stratification for liver disease severity using non-invasive biomarkers.
  2. To establish the incidence of liver and cardiovascular morbidity and mortality in a community cohort.
  3. To explore the quantitative and qualitative indicators to potential alterations in patient lifestyle following stratification of liver disease to inform future intervention development.
  4. To evaluate novel blood markers of liver fibrosis and cirrhosis on a large cohort of primary care patients

Study Configuration:

Longitudinal Cohort Study with long-term follow up

Setting:

Primary Care, Nottingham

Number of Participants:

Prospective and consecutive recruitment in the East Midlands - approximately 500 patients per annum over a 4 year cohort inception period. Total anticipated cohort size 2,000 participants.

Description of Interventions:

  • Serum blood sampling (AST:ALT ratio, and serum stored for future liver biomarker development)
  • Transient Elastography (Fibroscan)
  • Qualitative Interviews (limited to approximately 30 patients)
  • Consent to longitudinal data follow-up and approach for future lifestyle intervention trials - consenting patients will be tagged on MRIS database.

Duration of Study:

48 month cohort inception with long term longitudinal follow up of cardiovascular and liver related outcomes and mortality data.

Outcome Measures:

  1. Incidence of liver (cirrhosis) and cardiovascular disease (symptomatic coronary or cerebrovascular disease).
  2. All cause morbidity and mortality.
  3. Quantitative and qualitative lifestyle measures (including body mass index, exercise levels, alcohol consumption).

Patients who decide to participate in the community cohort will not be required to perform any specific actions or attend study visits (unless for the reasons stated below). Usual clinical care (both liver-related and non-liver related) will continue during the study period.

Patients will consent to long term longitudinal data follow-up using the Medical Research Information Service (MRIS) database. All patients enrolled in the community cohort will be prospectively tagged on MRIS. In particular, the investigators will request individual patient alerts on MRIS concerning prevalent cardiovascular disease events (angina, myocardial infarction and stroke), liver cirrhosis and cause of death.

Patients will consent to undertake qualitative research to evaluate the process of community stratification. A purposeful sample of patients completing the community biomarkers pathway will be invited to participate in qualitative follow up of their experiences of the pathway and any subsequent lifestyle change. A researcher, trained in qualitative research methods, will perform a semi-structured interview, which will assess any lifestyle changes occurring following liver pathway stratification. Specifically, changes in alcohol consumption, diet and exercise will be explored and evaluated, with assessment of the relationship to liver pathway stratification (both investigation results and lifestyle advice offered during the pathway). Interviews will performed either face-to-face, in which case this will be performed at the Nottingham Digestive Diseases Biomedical Research Unit, or over the telephone - in all cases voice recording will occur to allow analysis of information provided. An example interview proforma to be utilized for these qualitative interviews has been provided separately.

Patients will be consented to donate biosamples (including blood and urine) to the Nottingham Health Sciences Biobank on inception into the cohort. An appointment will be made at the NIHR Nottingham Digestive Diseases Biomedical Research Unit for witnessed written consent and to allow donation of biosamples. Samples will be collected by trained research nurses, who also form part of the research team. These biosamples will be utilized for future research into novel biomarkers of liver and cardiovascular disease, including proteomics and metabonomics. Where participants do not agree to the future use of the samples they will be destroyed in accordance with the Human Tissue Act, 2004.

In the future, the investigators will plan trials assessing novel exercise and dietary interventions, and subsequent effects on patient lifestyle parameters and future cardiovascular risk. Patients forming the community cohort will consent for contact regarding these future trials; however individual trials will be subject to their own ethical approval and written consent.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

A Primary Care database search (Systmone, TPP)will be performed to identify patients eligible for study (see inclusion criteria) in the discrete patient populations.

Criteria

Inclusion Criteria:

  • Adult patients aged 18 years or over (male or female) with primary risk factor for liver disease:

    • Hazardous alcohol use (>14 units/week for women, >21 units/week for men)
    • Type 2 Diabetes (with or without obesity)
    • Persistently elevated ALT with normal liver serology

Exclusion Criteria:

  • Active malignancy at study enrolment
  • Inability to provide informed consent for study enrolment
  • Known presence of histologically proven liver disease prior to pilot pathway participation
  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: NCT02037867

Locations
United Kingdom
Nottingham Digestive Diseases Biomedical Research Unit Recruiting
Nottingham, Notts, United Kingdom, NG7 2UH
Contact: Neil Guha, MRCP, PhD    01159249924 ext 70609    neil.guha@nottingham.ac.uk   
Contact: David J Harman, BMedSci, BMBS    01159249924 ext 70610    david.harman@nottingham.ac.uk   
Principal Investigator: Neil Guha, MRCP, PhD         
Sub-Investigator: David J Harman, BMedSci, BMBS         
Sub-Investigator: Guruprasad P Aithal, FRCP, PhD         
Sub-Investigator: Stephen D Ryder, MRCP, PhD         
Sub-Investigator: Martin W James, MRCP, PhD         
Sub-Investigator: Emilie A Wilkes, MRCP, PhD         
Sponsors and Collaborators
University of Nottingham
Investigators
Principal Investigator: Neil Guha, MRCP, PhD University of Nottingham
  More Information

Additional Information:
No publications provided

Responsible Party: University of Nottingham
ClinicalTrials.gov Identifier: NCT02037867     History of Changes
Other Study ID Numbers: 13GA006, 13/EM/0123
Study First Received: January 14, 2014
Last Updated: January 15, 2014
Health Authority: United Kingdom: National Institute for Health Research
United Kingdom: University of Nottingham

Keywords provided by University of Nottingham:
alcohol
type 2 diabetes
ALT
abnormal liver enzymes
hepatic fibrosis
cirrhosis

Additional relevant MeSH terms:
Alcohol Drinking
Diabetes Mellitus
Diabetes Mellitus, Type 2
Liver Diseases
Drinking Behavior
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Digestive System Diseases

ClinicalTrials.gov processed this record on August 21, 2014