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A Study of Novel Biomarkers of Kidney Dysfunction at Liver Transplant

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. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03376009
Recruitment Status : Unknown
Verified December 2017 by University of Edinburgh.
Recruitment status was:  Not yet recruiting
First Posted : December 18, 2017
Last Update Posted : December 18, 2017
Sponsor:
Collaborator:
NHS Lothian
Information provided by (Responsible Party):
University of Edinburgh

Brief Summary:

Kidney dysfunction before and immediately after liver transplantation is common and leads to poorer outcomes, including prolonged need for post-operative intensive care, diminished graft survival, and greater risk of permanent kidney dysfunction and death. Blood creatinine level - the standard measure of kidney function - is suboptimal in people with advanced liver disease, overestimating kidney function by >20%. There is significant concern that liver transplant recipients are at higher risk of acute kidney injury (AKI) than we can currently predict. This study aims to identify superior tests (blood/urine or imaging) for kidney dysfunction, to enable improved treatment and patient outcomes.

This study aims to recruit 80-100 consecutive patients admitted to the Scottish Liver Transplant Unit (SLTU), Royal Infirmary of Edinburgh (RIE) for liver transplant assessment over a 6 month period. Permission will be sought to record the results of routine tests performed by the NHS during this assessment week. These tests include: electrocardiograph (ECG), Computed Tomography (CT) liver and abdomen, cardio-pulmonary exercise testing (CPEX), pulmonary function tests (PFTS), routine haematology and biochemistry blood tests, 24 hour urine collection and body composition analysis.

In addition, we will invite participants to attend the RIE clinical research facility (CRF) for a single visit (~2 hours) to perform extra research assessments. Blood and urine will be collected for biomarker analysis. Non-invasive assessment of cardiovascular function will be completed using cardiac bio-impedance and aortic pulse wave velocity. Examination of the blood vessels at the back of the eye will be performed using optical coherence tomography.

A subgroup of 10 participants will undergo magnetic resonance imaging (MRI) of the kidneys using arterial spin labelling to identify dysregulated renal perfusion. Patients who are transplanted during the study timeframe will be asked to re-attend the CRF for repeat assessments at 6 weeks post transplantation.

Funded by Scottish Liver Transplant Unit Endowment Fund


Condition or disease Intervention/treatment
Liver Transplantation Liver Transplant; Complications Kidney Dysfunction Diagnostic Test: Blood sample for serum and plasma biomarkers: Diagnostic Test: Urine sample for biomarkers Diagnostic Test: Cardiac bio-impedance (Cardioscreen Medis) Diagnostic Test: Aortic pulse wave velocity (APWV) (TensioMed and SphygmoCor) Diagnostic Test: Optical Coherence Tomography (Spectralis OCT) Diagnostic Test: Arterial Spin Labelling Magnetic Resonance Imaging

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Study Type : Observational
Estimated Enrollment : 100 participants
Observational Model: Case-Only
Time Perspective: Prospective
Official Title: A Study of Novel Biomarkers of Kidney Dysfunction in Patients Admitted for Liver Transplant Assessment.
Estimated Study Start Date : January 2018
Estimated Primary Completion Date : April 2018
Estimated Study Completion Date : April 2019

Resource links provided by the National Library of Medicine


Group/Cohort Intervention/treatment
Liver transplant assessment patients

Adult patients admitted to the Scottish Liver Transplant Unit for liver transplant assessment, over a 6 month study period will be considered for recruitment.

Interventions:

Blood sample for serum and plasma biomarkers:

Urine sample for biomarkers Cardiac bio-impedance (Cardioscreen Medis) Aortic pulse wave velocity (APWV) (TensioMed and SphygmoCor) Optical Coherence Tomography (Spectralis OCT) Arterial Spin Labelling Magnetic Resonance Imaging

Diagnostic Test: Blood sample for serum and plasma biomarkers:
Serum/plasma biomarkers: Approximately 10ml (3 teaspoons) of blood will be extracted to measure pre-specified biomarkers of renal injury including kidney injury molecule-1 (KIM-1), cystatin C and neutrophil gelatinase-associated lipocalin (NGAL). Samples will then be stored to facilitate measurement of additional biomarkers in the future.

Diagnostic Test: Urine sample for biomarkers
Urinary biomarkers: A random urine sample will be obtained to measure urinary protein to creatinine ratio (uPCR), KIM-1 and liver-type fatty acid binding protein (L-FABP)

Diagnostic Test: Cardiac bio-impedance (Cardioscreen Medis)
Cardiac bio-impedance - a non-invasive assessment of cardiac output, cardiac index and systemic vascular resistance index using the bio-impedence technique (Cardioscreen 1000 Medis) Cardiac bio-impedance is performed by attaching sticky electrodes to the participant's neck and thorax. These electrodes pass a very low, constant and alternating current (1.5 mA, 86 kHz) across the thorax, which is imperceptible to the patient. This provides beat by beat data on cardiac output and haemodynamic measurements.

Diagnostic Test: Aortic pulse wave velocity (APWV) (TensioMed and SphygmoCor)

Aortic pulse wave velocity (APWV) a non-invasive measure of arterial function using oscillometric recordings to detail peripheral and central haemodynamics. This will be measured using two different techniques:

TensioMed Arteriograph: After a rest period a blood pressure cuff inflates and deflates twice on the arm. This takes ~3 minutes and should cause only mild, temporary discomfort. The test will routinely be performed in duplicate to ensure accuracy of results.

SphygmoCor: A pressure sensor is held over the radial pulse at the wrist to analyse the pulse wave. Then held over the carotid artery and/or femoral artery to assess the speed of the pulse wave through the body. The probe is similar to an ultrasound probe and should not cause any discomfort.


Diagnostic Test: Optical Coherence Tomography (Spectralis OCT)

OCT is a non-invasive imaging test which uses light waves to take cross sectional images of the back of the eye. Examination of the retinal and retinal nerve fibre layer thickness, macular volume, and choroidal thickness provides an assessment of generalised systemic microvascular injury. A strong correlation between choroidal thickness and renal dysfunction has previously been shown in patients with chronic kidney disease (Balmforth C et al, JCI Insight 2016).

The participant is asked to sit in front of the OCT machine and rest their chin on a support to keep it motionless. The equipment will then scan the eye without touching it. Scanning takes about 5 - 10 minutes.


Diagnostic Test: Arterial Spin Labelling Magnetic Resonance Imaging

Magnetic resonance imaging using arterial spin labelling (ASL-MRI) This promising quantitative technique has the potential to identify dysregulated renal perfusion, stratify risk of AKI in pre-OLT patients, and to monitor alterations in renal haemodynamics in the post transplantation setting.

  • We aim to recruit 5 participants with 'normal' renal function (eGFR≥60ml/min/1.73m2) and a further 5 participants with 'abnormal' renal function (eGFR<60ml/min/1.73m2)
  • ASL-MRI will be performed in this subgroup during the week of OLT assessment and then repeated at 6-weeks post transplantation in those participants who undergo OLT during the study period.
Other Name: ASL-MRI




Primary Outcome Measures :
  1. Relationship between pre-transplant kidney function using novel biomarkers and post-transplant morbidity and mortality. [ Time Frame: 6 months ]
    (KIM-1, NGAL, Cystatin C)


Secondary Outcome Measures :
  1. Relationship between pre-transplant kidney perfusion using non-contrast ASL-MRI and pre-transplant renal dysfunction defined by eGFR [ Time Frame: 7 days ]
    non-contrast Arterial spin labelling Magnetic Resonance Imaging (ASL-MRI)

  2. Relationship between pre-transplant kidney perfusion using non-contrast ASL-MRI and post-transplant renal dysfunction defined by eGFR [ Time Frame: 6 months ]
    non-contrast Arterial spin labelling Magnetic Resonance Imaging (ASL-MRI)

  3. Relationship between pre-transplant cardiac bioimpedence and post-transplant renal dysfunction [ Time Frame: 6 months ]
    Cardiac bioimpedence using cardioscreen medis

  4. Relationship between pre-transplant APWV and post-transplant renal dysfunction [ Time Frame: 6 months ]
    Aortic pulse wave velocity (APWV)

  5. Relationship between pre-transplant plasma KIM-1 and post-transplant renal dysfunction [ Time Frame: 6 months ]
    plasma KIM-1- biomarker of renal injury

  6. Relationship between pre-transplant urinary protein to creatinine ratio and post-transplant renal dysfunction [ Time Frame: 6 months ]
    urinary protein to creatinine ratio- urinary biomarker of renal injury

  7. Relationship between retinal nerve fibre layer, choroidal thickness and pre-transplant renal function [ Time Frame: 7 days ]
    Optical coherence tomography

  8. Relationship between pre-transplant haemodynamic biomarkers and mortality at 1 year [ Time Frame: 1 year ]
    Haemodynamic biomarkers as evidenced by cardiac bio-impedence, aortic pulse wave velocity +/- ASL-MRI


Biospecimen Retention:   Samples Without DNA
Blood samples for serum and plasma Urine samples


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 and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Consecutive patients who are admitted to the Royal Infirmary of Edinburgh (RIE) liver unit for liver transplant assessment over a 6-month period will be invited to join this study. They will be identified as potentially eligible by a member of their clinical care team, and thereafter will be introduced to a member of the research study team and given a participant information sheet. At present, approximately 4-5 patients are admitted for transplant assessment per week, therefore we anticipate that recruitment over a 6-month period would provide a potential of 80-100 participants.
Criteria

Inclusion Criteria:

  • Male or female adults over 18 years of age
  • Able to provide written informed consent and able to understand and willing to comply with the requirements of the study
  • Admission for assessment for liver transplantation

Exclusion Criteria:

  • Patients who do not have capacity to consent
  • Patients being assessed for liver transplantation because of acute liver failure
  • Patients who are unwilling or unable to have an MRI scan will be excluded from the ASL-MRI study sub-group

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): NCT03376009


Contacts
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Contact: Fiona J Gifford, MBChB 07846602243 fiona.gifford@nhslothian.scot.nhs.uk
Contact: Jonathan A Fallowfield, PhD 0131 242 6655 Jonathan.Fallowfield@ed.ac.uk

Locations
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United Kingdom
Royal Infirmary of Edinburgh
Edinburgh, Scotland, United Kingdom, EH16 4SA
Contact: Fiona J Gifford, MBChB    07846602243    fiona.gifford@nhslothian.scot.nhs.uk   
Contact: Jonathan A Fallowfield, PhD    0131 242 6655    Jonathan.Fallowfield@ed.ac.uk   
Sub-Investigator: Peter C Hayes, PhD         
Sub-Investigator: Scott Semple, PhD         
Sub-Investigator: David Morris, PhD         
Sub-Investigator: Kenneth Simpson, PhD         
Sub-Investigator: Neeraj Dhaun, PhD         
Sponsors and Collaborators
University of Edinburgh
NHS Lothian
Investigators
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Principal Investigator: Jonathan A Fallowfield, PhD University of Edinburgh, NHS Lothian
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Responsible Party: University of Edinburgh
ClinicalTrials.gov Identifier: NCT03376009    
Other Study ID Numbers: AC1
First Posted: December 18, 2017    Key Record Dates
Last Update Posted: December 18, 2017
Last Verified: December 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: Anonymised IPD that underlie results in a publication will be available only on direct request from another researcher

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by University of Edinburgh:
Biomarker
Additional relevant MeSH terms:
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Renal Insufficiency
Kidney Diseases
Urologic Diseases