Trial document




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  DRKS00015866

Trial Description

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Title

MR‑Progression‑Evaluation of Chronic Kidney Disease

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Trial Acronym

MR-P-CKD

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URL of the Trial

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Brief Summary in Lay Language

Chronic Kidney Disease (CKD) is characterized by a chronic renal tissue damage and/or continuous renal function impairment due to various affections. In high-income countries an alarming 10-18% of the population is affected and is prone to a reduced quality of life as well as premature death (e.g. early-onset of a cardiovascular disease). The final stage of CKD is called end-stage renal disease (ESRD), and a renal replacement therapy (dialysis and/or renal transplantation) becomes mandatory, which poses an additional disproportional and major burden to public health. It is estimated that ESRD alone costs 1 trillion US-Dollar annually. In addition, no truly new therapy has been identified within the last 15 years, so that many European and international scientific societies are merging their efforts to identify a renal imaging biomarker to improve the clinical management of patients.
In this context, the autosomal dominant polycystic kidney disease (ADPKD) is often referred to as an ideal model to evaluate CKD. Around 12.5 million people are affected worldwide, and around 70% of the ADPKD patients have ESRD during or after the middle age. A causal therapy has not been verified yet, even though many interesting findings have been published recently. The lack of a quantitative and safe in‑vivo evaluation is evident and hinders the progression towards novel therapies.
The aim of this exploratory non-profit project is to enable novel renal non-invasive and non-contrast magnetic resonance imaging (MRI) techniques at 3 Tesla to assess renal structural and functional changes quantitatively during the early course of the ADPKD, as a model for CKD. In total, 120 early ADPKD stage patients and healthy subjects will undergo a sophisticated hydration protocol and the MRI acquisition will be synchronized with regards to the subject’s blood flow and respiration to meet the specific physiological conditions of kidneys. A continuous quality assurance and validation against nuclear medicine reference methods shall ensure reliable data quality.
First, 30 healthy subjects and 30 ADPKD patients shall be recruited to optimize the MRI protocols according to the physiological challenges. Thereafter, the optimized protocols will be settled and applied in a cross-sectional and longitudinal study on 30 ADPKD patients and 30 healthy control subjects. These ADPKD patients will undergo a validation against the reference methods to prove the full potential of the envisioned MRI protocols to assess pathophysiological changes during the early course of the ADPKD.
This project will provide essential insights into the progression and quantification of CKD, based on novel and safe renal MRI biomarkers, thus without the need of a contrast agent and/or an exposure to ionizing radiation, to enable improvements in the diagnosis and evaluation of therapy responses.

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Brief Summary in Scientific Language

Chronic Kidney Disease (CKD) is characterized by a chronic renal parenchymal damage and/or continuous decline in renal function due to various etiologies. In high-income countries 10‑18% of the population is affected and is prone to a reduced quality of life as well as premature death (e.g. early‑onset of a cardiovascular disease). The final stage of CKD is called end-stage renal disease (ESRD), and a renal replacement therapy (dialysis and renal transplantation) becomes mandatory, which poses an additional disproportional and major burden to public health. Therefore, many European and international societies are merging their efforts to identify a renal imaging biomarker to improve the clinical management of patients.
In this context, the autosomal dominant polycystic kidney disease (ADPKD) is often referred to as an ideal model for nephro‑prevention for CKD. Around 12.5 million people are affected worldwide, and around 70% of ADPKD patients have ESRD during or after the middle age. A causal therapy has not been verified yet, even though many interesting findings have been published recently. The lack of a quantitative and safe in‑vivo evaluation for the CKD is evident and impedes the progression towards novel therapies.
The aim of this exploratory non-profit project is to enable novel renal non-invasive and non-contrast-enhanced magnetic resonance imaging (MRI) techniques, such as T1‑mapping, diffusion weighted imaging, diffusion tensor imaging and magnetic resonance elastography, at 3 Tesla (T) to assess renal structural and functional changes quantitatively during the early course of the ADPKD, as a model for CKD. In total, 120 early ADPKD stage patients and healthy subjects will undergo a sophisticated hydration protocol and the MRI acquisition will be triggered with regards to the subject’s perfusion and respiration to meet the specific physiological conditions of kidneys. A continuous quality assurance and validation against reference methods, using 99mTc‑mercaptoacetyltriglycine (99mTc‑MAG3) and 51Cr‑ethylendiamine tetraacetate acid (51Cr‑EDTA), shall ensure reliable data quality.
First, 30 healthy subjects and 30 ADPKD patients shall be recruited to optimize the MRI protocols according to the physiological challenges. Thereafter, the optimized protocols will be settled and applied in a cross-sectional and longitudinal study on 30 ADPKD patients and 30 healthy control subjects. These ADPKD patients will undergo a validation against the given reference methods (99mTc‑MAG3 and 51Cr‑EDTA) to proof the full potential of the envisioned MRI protocols to assess pathophysiological changes during the early course of the ADPKD.
The principal investigators (Ewald Moser, Gere Sunder‑Plaßmann), project partners (Gertraud Heinz, Anton Staudenherz, Ralph Sinkus) and consecutive personnel are prepared to supply the necessary infrastructure (e.g., state-of-the-art 3T scanners) and resources to manage all given tasks.
This project will provide essential insights into the progression and quantification of CKD based on novel and safe renal MRI biomarkers.

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Organizational Data

  •   DRKS00015866
  •   2018/12/05
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  •   yes
  •   Approved
  •   1477/2016, Ethikkommission der Medizinischen Universität Wien
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Secondary IDs

  •   U1111-1223-9974 
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Health Condition or Problem studied

  •   Q61.2 -  Polycystic kidney, autosomal dominant
  •   N18 -  Chronic kidney disease
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Interventions/Observational Groups

  •   Healthy Control Group 1 - Sequence optimization on 30 healthy subjects will be asked not to drink or eat 12 hours before MRI (T1-mapping, diffusion weighted imaging, diffusion tensor imaging, elastography) evaluation. After rehydration the MRI evaluation will be repeated.
  •   Sequence optimization on 30 ADPKD subjects will be asked not to drink or eat 12 hours before MRI (T1-mapping, diffusion weighted imaging, diffusion tensor imaging, elastography) evaluation. After rehydration the MRI evaluation will be repeated.
  •   Longitudinal Study on 30 ADPKD subjects. First measurements: Patients will be asked not to drink or eat 12 hours before MRI (T1-mapping, diffusion weighted imaging, diffusion tensor imaging, elastography) evaluation. After rehydration the MRI evaluation will be repeated.
    In addition, participants will undergo a renal function scintigraphy (99mTc‑MAG3 and 51Cr‑EDTA).
    Second measurement: Patients will be asked not to drink or eat 12 hours before MRI (T1-mapping, diffusion weighted imaging, diffusion tensor imaging, elastography) evaluation. After rehydration the MRI evaluation will be repeated.
    In addition, participants will undergo a renal function scintigraphy (99mTc‑MAG3 and 51Cr‑EDTA).
  •   Healthy Control Group 2 - Sequence optimization on 30 healthy subjects will be asked not to drink or eat 12 hours before MRI (T1-mapping, diffusion weighted imaging, diffusion tensor imaging, elastography) evaluation. After rehydration the MRI evaluation will be repeated.
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Characteristics

  •   Non-interventional
  •   Observational study
  •   Non-randomized controlled trial
  •   Open (masking not used)
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  •   Other
  •   Prevention
  •   Parallel
  •   N/A
  •   N/A
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Primary Outcome

Reproducibility and alteration of quantitative T1 relaxation time, apparent diffusion constant, fractional anisotropy, and Stiffness due to fluid intake (z.B. Wasser, Fruchtsäfte) on healthy and ADPKD subjects.

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Secondary Outcome

Alterations and Correlations during the course of the ADPKD.

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Countries of Recruitment

  •   Austria
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Locations of Recruitment

  • University Medical Center 
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Recruitment

  •   Planned
  •   2019/01/01
  •   120
  •   Monocenter trial
  •   National
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Inclusion Criteria

  •   Both, male and female
  •   18   Years
  •   39   Years
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Additional Inclusion Criteria

healthy subjects: 18-39 years of age, Body Mass Index (BMI) between 17-30kg/m² and Cockcroft-Gault or MDRD estimate of creatinine clearance >70mL/min (based on medical reports not older than two years; otherwise blood will be drawn for a new evaluation).

ADPKD subjects: 18-39 years of age, diagnosis ADPKD (type I or II) based on a positive family history and/or at least three kidney cysts (unilateral or bilateral), BMI between 17-30kg/m², Cockcroft-Gault or MDRD estimate of creatinine clearance >70mL/min (based on medical reports not older than two years; otherwise blood will be drawn), no albuminuria, and total cystic volume under 350mL and 450mL for women and men, respectively. Participants with a disputable ADPKD diagnosis or unmeasured kidney and cysts dimensions will be able to undergo an MRI evaluation, in order to prevent subjects to undergo an unnecessary renal function scintigraphy test.

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Exclusion Criteria

healthy subjects: pregnancy, breast feeding, mean seated blood pressure above 145/95mmHg and seated heart rate above 100 beats per second, diabetes mellitus (fasting glucose >126mg/dl, treatment with insulin or oral hypoglycemics), known atrial fibrillation or atrioventricular block grade II or higher, history of myocardial infarction, unstable angina pectoris, evident congestive heart failure (New York Heart Association class III/IV), established renal impairment or chronic disease potentially affecting renal function, and intake of antihypertensive medication, nonsteroidal antiinflammatory drugs like acetylsalicylic acid or diuretics, implants, which are not safe for 3T.

ADPKD subjects: pregnancy, breast feeding, mean seated blood pressure above 160/100mmHg and seated heart rate above 100 beats per minute, diabetes mellitus (fasting glucose >126mg/dl, treatment with insulin or oral hypoglycemics), known atrial fibrillation or atrioventricular block grade II or higher, history of myocardial infarction, unstable angina pectoris, evident congestive heart failure (New York Heart Association class III/IV), established moderate renal impairment (GFR category G3a or higher and albuminuria category A2 or higher) or other systemic diseases potentially affecting renal function, intake of nonsteroidal antiinflammatory drugs like acetylsalicylic acid or diuretics, and previous renal surgery or cyst drainage procedures, implants, which are not safe for 3T..

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Addresses

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    • Medizinische Universität Wien
    • Medizinische Universität Wien
    • 1090  Wien
    • Austria
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    • Medizinische Universität WienZentrum für Medizinische Physik und Biomedizinische Technik
    • Mr.  Dr.med.univ.  Marcos  Wolf 
    • Währinger Gürtel 18-20
    • 1090  Wien
    • Austria
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    • Medizinische Univeristät WienZentrum für Medizinische Physik und Biomedizinische Technik
    • Mr.  Dr.med.univ.  Marcos  Wolf 
    • Währinger Gürtel 18-20
    • 1090  Wien
    • Austria
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Sources of Monetary or Material Support

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    • FWF Der Wissenschaftsfond
    • Sensengasse 1
    • 1090  Wien
    • Austria
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Status

  •   Recruiting planned
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Trial Publications, Results and other Documents

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* This entry means the parameter is not applicable or has not been set.