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Prognostic Imaging Biomarkers for Diabetic Kidney Disease (iBEAt)

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ClinicalTrials.gov Identifier: NCT03716401
Recruitment Status : Recruiting
First Posted : October 23, 2018
Last Update Posted : October 23, 2018
Sponsor:
Collaborators:
University of Exeter
University of Bordeaux
University of Bari
University of Turku
Lund University
Swiss Institute of Bioinformatics
Information provided by (Responsible Party):
Steven Sourbron, University of Leeds

Brief Summary:

Diabetic kidney disease (DKD) is a common complication of diabetes, and is now the most common form of chronic kidney disease. DKD is the leading cause of kidney disease requiring dialysis or kidney transplantation, and its global incidence and prevalence have reached epidemic levels. While the risk of developing DKD can be ameliorated by tight blood glucose and blood pressure control, it is not fully preventable and once established DKD cannot be cured. Therefore many patients are left with poor and worsening health and with increased mortality risk. Developing new ways to treat DKD requires healthcare professionals to be able to identify those patients most in need of treatment.

One promising approach for identifying patients that are at risk is the use of imaging measurements (called "biomarkers") derived from Magnetic Resonance Imaging (MRI) and Ultrasound (US) of the kidneys. Evidence from early studies shows that such imaging biomarkers can identify underlying problems in DKD such as blood supply, oxygen supply, kidney scarring and kidney function, in ways that are better than those currently available.

The investigators think that imaging biomarkers will improve the identification of patients who are likely to decline from DKD in the short term. The changes found by imaging may even happen before effects on the blood and urine.

The investigators plan to test this hypothesis by performing a study observing 500 patients with early stage DKD, recruited in 5 sites across Europe. All patients will have detailed assessment at the start of their involvement, including clinical assessment, blood and urine samples, and MRI and US scans. The investigators will look at whether imaging biomarkers are associated with other measures that predict progression in DKD, and follow patients every year for 3 years (4 years total study participation) to see if the imaging biomarkers predict worsening DKD.


Condition or disease Intervention/treatment
Diabetic Kidney Disease Diagnostic Test: MRI (magnetic resonance imaging) Diagnostic Test: US (ultrasound) Procedure: Renal Biopsy Diagnostic Test: Positron Emission Tomography (PET) Diagnostic Test: Microvascular Assessment

  Show Detailed Description

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Study Type : Observational
Estimated Enrollment : 500 participants
Observational Model: Cohort
Time Perspective: Cross-Sectional
Official Title: Prognostic Imaging Biomarkers for Diabetic Kidney Disease
Actual Study Start Date : September 1, 2018
Estimated Primary Completion Date : September 1, 2020
Estimated Study Completion Date : September 1, 2038

Resource links provided by the National Library of Medicine


Group/Cohort Intervention/treatment
Bari: Biopsy Arm

All study participants will undergo a baseline MRI and US and corresponding blood and urine sample collection. This will be followed up annually for additional blood and urine samples.

Additionally, participants at the Bari site will have an additional renal biopsy at baseline.

Diagnostic Test: MRI (magnetic resonance imaging)
An MRI (or magnetic resonance imaging) scan is a radiology technique that uses magnetism, radio waves, and a computer to produce images of body structures. The MRI scanner is a tube surrounded by a circular magnet.

Diagnostic Test: US (ultrasound)
An ultrasound scan is a medical test that uses high-frequency sound waves to capture live images from the inside of the body.
Other Name: Sonography

Procedure: Renal Biopsy
A kidney biopsy involves taking one or more tiny pieces (samples) of the kidney to look at with special microscopes. The microscopes make it possible to see the samples in greater detail.
Other Names:
  • Kidney biopsy
  • percutaneous renal biopsy

Bordeaux: MRI Follow-up arm

All study participants will undergo a baseline MRI and US and corresponding blood and urine sample collection. This will be followed up annually for additional blood and urine samples.

Additionally, participants at the Bordeaux site will have an additional ultrasound US and MRI in Follow-up year 2.

Diagnostic Test: MRI (magnetic resonance imaging)
An MRI (or magnetic resonance imaging) scan is a radiology technique that uses magnetism, radio waves, and a computer to produce images of body structures. The MRI scanner is a tube surrounded by a circular magnet.

Diagnostic Test: US (ultrasound)
An ultrasound scan is a medical test that uses high-frequency sound waves to capture live images from the inside of the body.
Other Name: Sonography

Exeter: Microvascular arm

All study participants will undergo a baseline MRI and US and corresponding blood and urine sample collection. This will be followed up annually for additional blood and urine samples.

Participants at the Exeter site will undergo microvascular measurements including estimating glycocalyx thickness at baseline and at 2 years follow-up.

Diagnostic Test: MRI (magnetic resonance imaging)
An MRI (or magnetic resonance imaging) scan is a radiology technique that uses magnetism, radio waves, and a computer to produce images of body structures. The MRI scanner is a tube surrounded by a circular magnet.

Diagnostic Test: US (ultrasound)
An ultrasound scan is a medical test that uses high-frequency sound waves to capture live images from the inside of the body.
Other Name: Sonography

Diagnostic Test: Microvascular Assessment
Glycocalyx (a network of membrane proteoglycans and glycoproteins lining all blood vessels) thickness is non-invasively estimated from video clips of sublingual vessels captured using a hand held microscope. Glycocalyx is vital for vascular health; perturbations in the glycocalyx are thought to contribute to numerous vascular health complications including DKD.

Leeds: Microstructure MRI arm

All study participants will undergo a baseline MRI and US and corresponding blood and urine sample collection.

Participants at the Leeds' site will have an extended MRI scan at baseline including novel microstructure MRI measurements.

Diagnostic Test: MRI (magnetic resonance imaging)
An MRI (or magnetic resonance imaging) scan is a radiology technique that uses magnetism, radio waves, and a computer to produce images of body structures. The MRI scanner is a tube surrounded by a circular magnet.

Diagnostic Test: US (ultrasound)
An ultrasound scan is a medical test that uses high-frequency sound waves to capture live images from the inside of the body.
Other Name: Sonography

Turku: PET arm

All study participants will undergo a baseline MRI and US and corresponding blood and urine sample collection. This will be followed up annually for additional blood and urine samples.

Additionally, participants at the Turku site will undergo a renal Positron Emission Tomography (PET) scan at the baseline timepoint.

Diagnostic Test: MRI (magnetic resonance imaging)
An MRI (or magnetic resonance imaging) scan is a radiology technique that uses magnetism, radio waves, and a computer to produce images of body structures. The MRI scanner is a tube surrounded by a circular magnet.

Diagnostic Test: US (ultrasound)
An ultrasound scan is a medical test that uses high-frequency sound waves to capture live images from the inside of the body.
Other Name: Sonography

Diagnostic Test: Positron Emission Tomography (PET)
Positron emission tomography (PET) uses small amounts of radioactive materials called radiotracers, a special camera and a computer to help evaluate organ and tissue functions. By identifying body changes at the cellular level, PET may detect the early onset of disease before it is evident on other imaging tests.
Other Name: PET scan




Primary Outcome Measures :
  1. Cross-sectional (multi-centre collaboration) [ Time Frame: 2 years ]
    MRI biomarkers will be combined with fluid-based biomarkers to discover radiomics features that correlate with renal function


Secondary Outcome Measures :
  1. Longitudinal (multi-centre collaboration) [ Time Frame: 4 years ]
    MRI biomarkers will be combined with patient follow-up data to discover radiomics features that correlate with disease progression


Other Outcome Measures:
  1. Turku PET Cohort - Renal Blood Flow [ Time Frame: 2 years ]
    Renal Blood Flow measured by Water-labelled PET/MRI

  2. Bari Biopsy Cohort - Total number of glomeruli [ Time Frame: 2 years ]
    Total number of glomeruli measured on renal histopathology

  3. Leeds Microstructure MRI Cohort - Novel biomarkers of renal microstructure [ Time Frame: 2 years ]
    Novel biomarkers of renal microstructure measured with Diffusion Tensor Imaging and 3D Dynamic Contrast-Enhanced MRI

  4. Bordeaux MRI Follow-up Cohort - two-year rate of change in MRI biomarkers and radiomic signatures [ Time Frame: 4 years ]
    Two-year rate of change in MRI biomarkers and radiomic signatures

  5. Exeter Microvasculature Assessment Cohort - Thickness of the sublingual glycocalyx [ Time Frame: 4 years ]
    Thickness of the sublingual glycocalyx as measured by Glycocheck imaging


Biospecimen Retention:   Samples With DNA
Blood and urine samples will be collected from all study participants, including serum, plasma, DNA, and RNA samples. A first morning and additional urine void are requested by all participants


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 to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
It is the goal of this study to be as inclusive of Type 2 Diabetes as possible, to create a heterogeneous population of participants in the effort to subcategorize to the greatest extent possible for cross-sectional analysis and potential biomarker identification.
Criteria

Inclusion Criteria:

  • Diagnosis Diabetes Type 2;
  • eGFR >= 30 ml/min/1.73m2;
  • Able to provide informed consent;
  • Age between 18 years and 80 years;
  • Unchanged antidiabetic and antihypertensive medication for the past 3 months (not including dose changes).

Exclusion Criteria:

  • Transplantation (except corneal);
  • On permanent dialysis;
  • Significant comorbidities with life expectancy of < 1 year;
  • Use of investigational drug within 1 month prior to screening;
  • Known clinical history of urinary obstruction on renal US: either post-voiding residue over 100 ml, or pyelectasis;
  • Known clinical history of aortic endoprosthesis at the renal level;
  • Current pregnancy;
  • History of Hepatitis B or Hepatitis C +;
  • Use of antiretroviral medication;
  • Known current or clinical history of renal or urinary tract malignancy;
  • Concurrent other renal disease (suspected or proven);
  • Cirrhotic liver disease, or non-cirrhotic chronic liver disease where ALT >2 x upper limit of normal;
  • Current metastatic malignancy;
  • Current malignancy with expected survival < study follow up period (4 years);
  • Melanomatous skin cancer < 5 years ago (fully resected melanoma >5 years ago, i.e. surgical cure, can be recruited);
  • Any other significant disease or disorder which, in the opinion of the investigators, may either put the patient at risk because of participation in the study, or may influence the result of the study, or the patient's ability to participate in the study;
  • Cochlear Implant;
  • Aneurysm Clips;
  • Neurological stimulator;
  • Implanted cardiac devices (ICD, PPM, loop recorders, or any others);
  • Metal heart valve;
  • History of metal foreign bodies in orbits;
  • Other implanted metal device which prevents MR imaging;
  • Known allergy to Gadolinium contrast;
  • Claustrophobia;
  • Weight exceeding 250 kg;
  • [Bari arm] Absolute contraindications to percutaneous renal biopsy;
  • [Bari arm] Bleeding diathesis;
  • [Bari arm] Severe uncontrolled hypertension;
  • [Bari arm] End stage renal disease with small hyperechoic kidneys;

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): NCT03716401


Contacts
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Contact: Steven Sourbron, PhD 0044-113-34-38003 s.sourbron@leeds.ac.uk
Contact: Chrysta C Lienczewski, BS 734-615-5021 boridley@umich.edu

Locations
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Finland
Turun Yliopisto Recruiting
Turku, Finland
Contact: Niina Koivuviita, MD       niina.koivuviita@tyks.fi   
Principal Investigator: Pirjo Nuutila, MD         
France
Centre Hospitalier Universitaire de Bordeaux Not yet recruiting
Bordeaux, France
Contact: Corinne Castermans       corinne.castermans@chu-bordeaux.fr   
Principal Investigator: Nicolas Grenier, MD         
Italy
Università degli Studi di Bari Aldo Moro Not yet recruiting
Bari, Puglia, Italy
Contact: Massimo Papale, PhD       mpapale78@gmail.com   
Principal Investigator: Loreto Gesualdo, MD         
Sweden
Lund University Diabetes Centre Active, not recruiting
Malmö, Sweden, 214 28
Switzerland
Swiss Institute of Bioinformatics Active, not recruiting
Lausanne, Switzerland, 1015
United Kingdom
University of Exeter Not yet recruiting
Exeter, United Kingdom
Contact: Kim Gooding, PhD       k.m.gooding@exeter.ac.uk   
Principal Investigator: Angela Shore, PhD         
University of Leeds Recruiting
Leeds, United Kingdom
Contact: Steven Sourbron, PhD       s.sourbron@leeds.ac.uk   
Principal Investigator: Steven Sourbron, PhD         
Sponsors and Collaborators
University of Leeds
University of Exeter
University of Bordeaux
University of Bari
University of Turku
Lund University
Swiss Institute of Bioinformatics
Investigators
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Study Chair: Steven sourbron University of Leeds

Additional Information:
Publications:
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Responsible Party: Steven Sourbron, Lecturer, University of Leeds
ClinicalTrials.gov Identifier: NCT03716401     History of Changes
Other Study ID Numbers: 219542
First Posted: October 23, 2018    Key Record Dates
Last Update Posted: October 23, 2018
Last Verified: October 2018

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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 Steven Sourbron, University of Leeds:
Magnetic Resonance Imaging
Ultrasound Imaging
Biomarkers
Prognosis

Additional relevant MeSH terms:
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Kidney Diseases
Diabetic Nephropathies
Urologic Diseases
Diabetes Complications
Diabetes Mellitus
Endocrine System Diseases