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VisR Ultrasound for Noninvasively Monitoring Renal Allograft Health

Completed
Conditions
Renal Transplant Failure
Registration Number
NCT03079882
Lead Sponsor
University of North Carolina, Chapel Hill
Brief Summary

Ten percent of American adults, more than 20 million people, have chronic kidney disease, which in the advanced state of end stage renal disease is most desirably and cost-effectively treated by kidney transplantation. However, 20-30% of transplanted kidneys fail in living recipients by 10 years, owing largely to insufficient monitoring methods. The goal of the proposed research is to improve noninvasive kidney transplant monitoring using a new ultrasound-based imaging method called Viscoelastic Response (VisR) ultrasound.

Detailed Description

Renal transplantation is the most desirable and cost effective treatment for end stage renal disease, but 20-30% of allografts fail in living recipients by 10 years, and prolonging graft health is one of the major unmet needs for transplant patients. Although graft health is extended by preemptive treatments that prevent irreversible damage, intervention is inadequately motivated by current transplant monitoring methods. Noninvasive methods, including changes in serial serum creatinine levels, lack sensitivity and specificity. In the absence of reliable noninvasive biomarkers, invasive biopsy remains the standard for assessing transplant health, but surveillance or "protocol" biopsies are associated with morbidity and cost and are therefore controversial in stable, unsensitized patients. The lack of a demonstrated, noninvasive biomarker for allograft health - one that identifies early graft degeneration with sufficient sensitivity and specificity to motivate appropriate biopsy and enable timely intervention - represents a major gap in renal transplant management.

To fill this gap, the proposed re-search aims to demonstrate Viscoelastic Response (VisR) ultrasound, a novel acoustic radiation force (ARF)-based technology that noninvasively interrogates the viscoelastic properties of tissue, for monitoring renal allograft health. The investigators hypothesize that in vivo VisR ultrasound delineates renal allograft dysfunction earlier and with greater sensitivity and specificity than serum creatinine concentration in renal allograft recipients.

To test this hypothesis, the investigators will determine which VisR outcome metrics detect renal allograft dysfunction clinically by performing serial VisR imaging in living donor (LD) and deceased donor (DD) transplant recipients. Imaging results will be compared to biopsy findings to determine VisR's ability to detect dysfunction. The investigators will also compare serial VisR and serum creatinine outcomes in terms of ability to detect renal allograft dysfunction and the timeliness of detection.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
65
Inclusion Criteria
  1. At least 18 years of age
  2. Selected by treating physician to be in need of renal transplant surgery
  3. Ability to provide informed consent
  4. Ability to communicate with pertinent staff
  5. Ability to understand and comply with study requirements
Exclusion Criteria
  1. Inability to provide valid consent

  2. Inability to communicate with pertinent staff

  3. Inability to remain motionless for at least 20 minutes

  4. Renal transplant deeper than 4 cm

Study & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
VisR AUC valueat time of clinically indicated biopsy

AUC for VisR to detect positive biopsy finding (indiscriminate of type)

Secondary Outcome Measures
NameTimeMethod
AUC for the ability of change in serum creatinine level to detect positive biopsy findingat time of clinically indicated biopsy

Receiver operating characteristic (ROC) curve analysis will be performed using pathology findings as the gold standard. From the ROC curve, AUC will be calculated.

AUC for the ability of change in VisR Tau value to detect positive biopsy findingat time of clinically indicated biopsy

Receiver operating characteristic (ROC) curve analysis will be performed using pathology findings as the gold standard. From the ROC curve, AUC will be calculated.

AUC for the ability of change in VisR Relative Elasticity value to detect positive biopsy findingat time of clinically indicated biopsy

Receiver operating characteristic (ROC) curve analysis will be performed using pathology findings as the gold standard. From the ROC curve, AUC will be calculated.

AUC for the ability of change in VisR Relative Viscosity value to detect positive biopsy findingat time of clinically indicated biopsy

Receiver operating characteristic (ROC) curve analysis will be performed using pathology findings as the gold standard. From the ROC curve, AUC will be calculated.

Change in serum creatinine level1-2 weeks, 4 weeks, 2 months, 3 months, 6 months, 9 months, 12 months, and then every 4 months after transplantation until time of clinically indicated biopsy or 3 years after transplantation, which ever comes first

serum creatine will be measured serially, consistent with clinical indication, and change in level from time point to time point will be recorded.

Change in VisR Tau value1-2 weeks, 4 weeks, 2 months, 3 months, 6 months, 9 months, 12 months, and then every 4 months after transplantation until time of clinically indicated biopsy or 3 years after transplantation, which ever comes first

VisR Tau will be measured serially, and change in values from time point to time point will be recorded.

Change in VisR Relative Elasticity value1-2 weeks, 4 weeks, 2 months, 3 months, 6 months, 9 months, 12 months, and then every 4 months after transplantation until time of clinically indicated biopsy or 3 years after transplantation, which ever comes first

VisR Relative Elasticity will be measured serially, and change in values from time point to time point will be recorded.

Change in VisR Relative Viscosity value1-2 weeks, 4 weeks, 2 months, 3 months, 6 months, 9 months, 12 months, and then every 4 months after transplantation until time of clinically indicated biopsy or 3 years after transplantation, which ever comes first

VisR Relative Viscosity will be measured serially, and change in values from time point to time point will be recorded.

AUC for the ability of VisR-derived Tau to detect positive biopsy findingat time of clinically indicated biopsy

Tau represents the relaxation time constant for constant stress in a Voigt material and reflects the ratio of viscous to elastic properties of the kidney in the examined region.

AUC for the ability of VisR-derived Relative Elasticity to detect positive biopsy findingat time of clinically indicated biopsy

Relative elasticity qualitatively represents the tissue elastic modulus relative to the applied force amplitude

AUC for the ability of VisR-derived Relative Viscosity to detect positive biopsy findingat time of clinically indicated biopsy

Relative viscosity qualitatively represents the tissue viscous modulus relative to the applied force amplitude

Trial Locations

Locations (1)

University of North Carolina at Chapel Hill

🇺🇸

Chapel Hill, North Carolina, United States

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