Multiparametric MRI in Healthy Volunteers and CKD Patients (RESPECT)

Exploratory Multicentre Clinical Study to Assess Repeatibility, Reproducibility, Acceptability and Clinical Validity of Multiparametric Renal Magnetic Resonance Imaging

Chronic kidney disease (CKD) is a global health concern because more than 10% of the world's population have it, its prevalence is increasing, and CKD is an important contributor to morbidity and mortality for this population.

The majority of the people with CKD aren't aware and there are not available tools for early CKD detection and for an accurate prediction on these patients. Many CKD patients exhibit progressive renal dysfunction, demonstrating a failure of current, non-specific therapeutic strategies. Better methods are urgently needed for i) early diagnosis of CKD, and prediction of its progression for improved stratification of patients and better targeting of current treatments; and ii) to directly assess structural and functional responses of the kidney to new therapies and identify those patients who respond.

Over the past decade, renal Magnetic Resonance Imaging (MRI) has emerged as a promising technique for improved understanding and characterisation of renal pathophysiology. Compared to histopathology, MRI is non-invasive and avoids sampling bias by characterising the entire kidney with high spatial resolution.

In spite of a number of single centre studies showing renal MRI feasibility and potential to address a number of key clinical questions, current methodological differences across studies hinder reliable comparisons of the results, which can only be regarded as preliminary. Standardization of acquisition and processing protocols across centres is therefore needed, and this will also lead to the possibility to provide preliminary data of the multiparametric renal MRI clinical validity and utility.

The purpose of this study is to standardize, assess the feasibility and provide preliminary evidence of clinical validity and utility of the multiparametric renal MRI.

To reach this goal two groups of subjects are involved:

• Group 1 (healthy volunteers). In this group the repeatibility and reproducibility of multiparametric renal MRI will be assessed.
• Group 2 (CKD patients). In this group the feasibility, the acceptability, the reproducibility and the preliminary clinical validity of multiparametric renal MRI will be assessed.

Study Overview

• Status: Recruiting
• Conditions: Healthy; Chronic Kidney Diseases
• Intervention / Treatment: Diagnostic test: Non- contrast Enhanced Multiparametric Renal Magnetic Resonance

• Study Type: Interventional
• Enrollment (Estimated): 140
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Anna Caroli; Phone Number: 003903545351; Email: anna.caroli@marionegri.it
• Study Contact Backup: Name: Michela Bozzetto; Phone Number: 003903545351; Email: michela.bozzetto@marionegri.it

Study Locations

• Denmark
  • Århus N, Denmark, 8200
    • Not yet recruiting
    • Aarhus University Hospital, Department of Renal Medicine
    • Contact: Niels Henrik Buus, MD; Email: nhb@biomed.au.dk
• Germany
  • Mannheim
    • Heidelberg, Mannheim, Germany
      • Not yet recruiting
      • University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University
      • Contact: Philipp Riffel, MD; Email: philipp.riffel@umm.de
• Italy
  • BG
    • Ranica, BG, Italy, 24020
      • Not yet recruiting
      • Centro di Ricerche Cliniche per le Malattie Rare "Aldo e Cele Daccò"
      • Contact: Matias Trillini, MD; Phone Number: 0039 035 45351; Email: matias.trillini@marionegri.it
• Spain
  • Navarra
    • Pamplona, Navarra, Spain, 31008
      • Recruiting
      • Clinica Universidad de Navarra
      • Contact: Nuria Garcia Fernandez, MD; Email: nrgarcia@unav.es

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

GROUP 1:

1. Provision of written informed consent prior to any study specific procedures
2. Male and female subjects aged more than18 years
3. Normotensive (office Systolic Blood Pressure values < 140 mmHg and Diastolic Blood Pressure values ≤ 90 mmHg)
4. Normal renal condition for age (established by estimating Glomerular Filtration Rate using CKD-EPI, Chronic Kidney Disease Epidemiology Collaboration, Creatinine Equation)
5. Negative result upon urine dipstick testing for haematuria or proteinuria.
6. Normal Urine Albumin-to-Creatinine Ratio (UACR) (<30 mg/g)

GROUP 2:

1. Provision of written informed consent prior to any study specific procedures
2. Male and female patients aged more than18 years
3. CKD stage 2 or 3, with albuminuria up to 2000 mg

Exclusion Criteria:

GROUP 1 and 2

1. Previous enrollment in the present study

2. Contraindications to MRI including due to:

   • Claustrophobia
   • Pregnancy
   • Cardiac pacemakers or other MRI-incompatible prostheses

Only GROUP 2:

1. Urine Albumin-to-Creatinine Ratio higher than 2000 mg/g or 24h urine total albumin >2 g
2. Polycystic kidney disease, renovascular disease, active/current nephrotic syndrome, reflux nephropathy and known congenital renal diseases or solitary kidney.
3. Active malignancy or acute or chronic inflammatory disease, HIV
4. Acute kidney injury, as defined by the the KDIGO guidelines, during the last three months.
5. Need of a new immunosuppressive therapy for treating renal disease relapse in the preceding three months.
6. Dialysis or kidney transplantation
7. CKD stages 4 or 5
8. New medication in the preceding two weeks (diuretic, hypertensive, SGLT2 treatment)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Healthy volunteers	Diagnostic test: Non- contrast Enhanced Multiparametric Renal Magnetic Resonance; MRI is performed in a single multiparametric scan session with no need for contrast agents, and to depict changes in tissue microstructure associated with inflammation and fibrosis plus alterations in oxygenation.
Experimental: CKD patients	Diagnostic test: Non- contrast Enhanced Multiparametric Renal Magnetic Resonance; MRI is performed in a single multiparametric scan session with no need for contrast agents, and to depict changes in tissue microstructure associated with inflammation and fibrosis plus alterations in oxygenation.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
GROUP 1: within subject total kidney volume coefficient of variation in few hour time	Within subject coefficient of variation of measures computed by multiparametric renal MRI repeated in few hour time to assess total kidney volume repeatability in the whole group of healthy volunteers	At day 0
GROUP 1: within subject total kidney volume coefficient of variation after 1-2 weeks	Within subject coefficient of variation of measures computed by multiparametric renal MRI repeated after 1-2 weeks to assess total kidney volume reproducibility in the whole group of healthy volunteers	At day 7-14
GROUP 1: within subject renal artery blood flow coefficient of variation in few hour time	Within subject coefficient of variation of measures computed by multiparametric renal MRI repeated in few hour time to assess renal artery blood flow repeatability in the whole group of healthy volunteers	At day 0
GROUP 1: within subject renal artery blood flow coefficient of variation after 1-2 weeks	Within subject coefficient of variation of measures computed by multiparametric renal MRI repeated after 1-2 weeks to assess renal artery blood flow reproducibility in the whole group of healthy volunteers	At day 7-14
GROUP 1: within subject cortical perfusion coefficient of variation in few hour time	Within subject coefficient of variation of measures computed by multiparametric renal MRI repeated in few hour time to assess cortical perfusion repeatability in the whole group of healthy volunteers	At day 0
GROUP 1: within subject cortical perfusion coefficient of variation after 1-2 weeks	Within subject coefficient of variation of measures computed by multiparametric renal MRI repeated after 1-2 weeks to assess cortical perfusion reproducibility in the whole group of healthy volunteers	At day 7-14
GROUP 1: within subject cortical and medullary T1 coefficient of variation in few hour time	Within subject coefficient of variation of measures computed by multiparametric renal MRI repeated in few hour time to assess cortical and medullary T1 repeatability in the whole group of healthy volunteers	At day 0
GROUP 1: within subject cortical and medullary T1 coefficient of variation after 1-2 weeks	Within subject coefficient of variation of measures computed by multiparametric renal MRI repeated after 1-2 weeks to assess cortical and medullary T1 reproducibility in the whole group of healthy volunteers	At day 7-14
GROUP 1: within subject cortical and medullary T2 coefficient of variation in few hour time	Within subject coefficient of variation of measures computed by multiparametric renal MRI repeated in few hour time to assess cortical and medullary T2 repeatability in the whole group of healthy volunteers	At day 0
GROUP 1: within subject cortical and medullary T2 coefficient of variation after 1-2 weeks	Within subject coefficient of variation of measures computed by multiparametric renal MRI repeated after 1-2 weeks to assess cortical and medullary T2 reproducibility in the whole group of healthy volunteers	At day 7-14
GROUP 1: within subject cortical and medullary R2* coefficient of variation in few hour time	Within subject coefficient of variation of measures computed by multiparametric renal MRI repeated in few hour time to assess cortical and medullary R2* repeatability in the whole group of healthy volunteers	At day 0
GROUP 1: within subject cortical and medullary R2* coefficient of variation after 1-2 weeks	Within subject coefficient of variation of measures computed by multiparametric renal MRI repeated after 1-2 weeks to assess cortical and medullary R2* reproducibility in the whole group of healthy volunteers	At day 7-14
GROUP 1: within subject cortical and medullary ADC coefficient of variation in few hour time	Within subject coefficient of variation of measures computed by multiparametric renal MRI repeated in few hour time to assess cortical and medullary ADC repeatability in the whole group of healthy volunteers	At day 0
GROUP 1: within subject cortical and medullary ADC coefficient of variation after 1-2 weeks	Within subject coefficient of variation of measures computed by multiparametric renal MRI repeated after 1-2 weeks to assess cortical and medullary ADC reproducibility in the whole group of healthy volunteers	At day 7-14
GROUP 2 - Percentage of complete renal MRI data collection and analysis	Percentage of complete renal MRI data acquired and generated by MRI data processing in the whole group of CKD patients, to assess feasibility of multiparametric renal MRI in CKD patients	At day 0

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
GROUP 1 - within subject renal total kidney volume coefficient of variation in few hour time by gender	Within subject coefficient of variation of measures computed by multiparametric renal MRI repeated in few hour time in male and female healthy volunteers to assess differences in total kidney volume repeatability between genders	At day 0
GROUP 1 - within subject renal artery blood flow coefficient of variation in few hour time by gender	Within subject coefficient of variation of measures computed by multiparametric renal MRI repeated in few hour time in male and female healthy volunteers to assess differences in renal artery blood flow repeatability between genders	At day 0
GROUP 1 - within subject cortical perfusion coefficient of variation in few hour time by gender	Within subject coefficient of variation of measures computed by multiparametric renal MRI repeated in few hour time in male and female healthy volunteers to assess differences in cortical perfusion repeatability between genders	At day 0
GROUP 1 - within subject cortical and medullary T1 coefficient of variation in few hour time by gender	Within subject coefficient of variation of measures computed by multiparametric renal MRI repeated in few hour time in male and female healthy volunteers to assess differences in cortical and medullary T1 repeatability between genders	At day 0
GROUP 1 - within subject cortical and medullary T2 coefficient of variation in few hour time by gender	Within subject coefficient of variation of measures computed by multiparametric renal MRI repeated in few hour time in male and female healthy volunteers to assess differences in cortical and medullary T2 repeatability between genders	At day 0
GROUP 1 - within subject cortical and medullary R2* coefficient of variation in few hour time by gender	Within subject coefficient of variation of measures computed by multiparametric renal MRI repeated in few hour time in male and female healthy volunteers to assess differences in cortical and medullary R2* repeatability between genders	At day 0
GROUP 1 - within subject cortical and medullary ADC coefficient of variation in few hour time by gender	Within subject coefficient of variation of measures computed by multiparametric renal MRI repeated in few hour time in male and female healthy volunteers to assess differences in cortical and medullary ADC repeatability between genders	At day 0
GROUP 1 - within subject total kidney volume coefficient of variation in few hour time by age	Within subject coefficient of variation of measures computed by multiparametric renal MRI repeated in few hour time in healthy volunteers of different age to assess differences in total kidney volume repeatability between age classes	At day 0
GROUP 1 - within subject renal artery blood flow coefficient of variation in few hour time by age	Within subject coefficient of variation of measures computed by multiparametric renal MRI repeated in few hour time in healthy volunteers of different age to assess difference in renal artery blood flow repeatability between age classes	At day 0
GROUP 1 - within subject cortical perfusion coefficient of variation in few hour time by age	Within subject coefficient of variation of measures computed by multiparametric renal MRI repeated in few hour time in healthy volunteers of different age to assess differences in cortical perfusion repeatability between age classes	At day 0
GROUP 1 - within subject cortical and medullary T1 coefficient of variation in few hour time by age	Within subject coefficient of variation of measures computed by multiparametric renal MRI repeated in few hour time in healthy volunteers of different age to assess differences in cortical and medullary T1 repeatability between age classes	At day 0
GROUP 1 - within subject cortical and medullary T2 coefficient of variation in few hour time by age	Within subject coefficient of variation of measures computed by multiparametric renal MRI repeated in few hour time in healthy volunteers of different age to assess differences in cortical and medullary T2 repeatability between age classes	At day 0
GROUP 1 - within subject cortical and medullary R2* coefficient of variation in few hour time by age	Within subject coefficient of variation of measures computed by multiparametric renal MRI repeated in few hour time in healthy volunteers of different age to assess differences in cortical and medullary R2* repeatability between age classes	At day 0
GROUP 1 - within subject cortical and medullary ADC coefficient of variation in few hour time by age	Within subject coefficient of variation of measures computed by multiparametric renal MRI repeated in few hour time in healthy volunteers of different age to assess differences in cortical and medullary ADC repeatability between age classes	At day 0
GROUP 1 - within subject total kidney volume coefficient of variation after 1-2 weeks by gender	Within subject coefficient of variation of measures computed by multiparametric renal MRI repeated after 1-2 weeks in male and female healthy volunteers to assess differences in total kidney volume reproducibility between genders	At day 7-14
GROUP 1 - within subject renal artery blood flow coefficient of variation after 1-2 weeks by gender	Within subject coefficient of variation of measures computed by multiparametric renal MRI repeated after 1-2 weeks in male and female healthy volunteers to assess differences in renal artery blood flow reproducibility between genders	At day 7-14
GROUP 1 - within subject cortical perfusion coefficient of variation after 1-2 weeks by gender	Within subject coefficient of variation of measures computed by multiparametric renal MRI repeated after 1-2 weeks in male and female healthy volunteers to assess differences in cortical perfusion reproducibility between genders	At day 7-14
GROUP 1 - within subject cortical and medullary T1 coefficient of variation after 1-2 weeks by gender	Within subject coefficient of variation of measures computed by multiparametric renal MRI repeated after 1-2 weeks in male and female healthy volunteers to assess difference in cortical and medullary T1 reproducibility between genders	At day 7-14
GROUP 1 - within subject cortical and medullary T2 coefficient of variation after 1-2 weeks by gender	Within subject coefficient of variation of measures computed by multiparametric renal MRI repeated after 1-2 weeks in male and female healthy volunteers to assess differences in cortical and medullary T2 reproducibility between genders	At day 7-14
GROUP 1 - within subject cortical and medullary R2* coefficient of variation after 1-2 weeks by gender	Within subject coefficient of variation of measures computed by multiparametric renal MRI repeated after 1-2 weeks in male and female healthy volunteers to assess differences in cortical and medullary R2* reproducibility between genders	At day 7-14
GROUP 1 - within subject cortical and medullary ADC coefficient of variation after 1-2 weeks by gender	Within subject coefficient of variation of measures computed by multiparametric renal MRI repeated after 1-2 weeks in male and female healthy volunteers to assess differences in cortical and medullary ADC reproducibility between genders	At day 7-14
GROUP 1 - within subject total kidney volume coefficient of variation after 1-2 weeks by age	Within subject coefficient of variation of measures computed by multiparametric renal MRI repeated after 1-2 weeks in healthy volunteers of different age to assess differences in total kidney volume reproducibility between age classes	At day 7-14
GROUP 1 - within subject renal artery blood flow coefficient of variation after 1-2 weeks by age	Within subject coefficient of variation of measures computed by multiparametric renal MRI repeated after 1-2 weeks in healthy volunteers of different age to assess differences in renal artery blood flow reproducibility between age classes	At day 7-14
GROUP 1 - within subject cortical perfusion coefficient of variation after 1-2 weeks by age	Within subject coefficient of variation of measures computed by multiparametric renal MRI after 1-2 weeks in healthy volunteers of different age to assess differences in cortical perfusion reproducibility between age classes	At day 7-14
GROUP 1 - within subject cortical and medullary T1 coefficient of variation after 1-2 weeks by age	Within subject coefficient of variation of measures computed by multiparametric renal MRI after 1-2 weeks in healthy volunteers of different age to assess differences in cortical and medullary T1 reproducibility between age classes	At day 7-14
GROUP 1 - within subject cortical and medullary T2 coefficient of variation after 1-2 weeks by age	Within subject coefficient of variation of measures computed by multiparametric renal MRI after 1-2 weeks in healthy volunteers of different age to assess differences in cortical and medullary T2 reproducibility between age classes	At day 7-14
GROUP 1 - within subject cortical and medullary R2* coefficient of variation after 1-2 weeks by age	Within subject coefficient of variation of measures computed by multiparametric renal MRI after 1-2 weeks in healthy volunteers of different age to assess differences in cortical and medullary R2* reproducibility between age classes	At day 7-14
GROUP 1 - within subject cortical and medullary ADC coefficient of variation after 1-2 weeks by age	Within subject coefficient of variation of measures computed by multiparametric renal MRI after 1-2 weeks in healthy volunteers of different age to assess differences in cortical and medullary ADC reproducibility between age classes	At day 7-14
GROUP 1 - Multiparametric MRI acceptability in healthy volunteers.	Multiparametric MRI acceptability, in terms of comfort level and degree of satisfaction, assessed by a specific 9-item questionnaire ([9-45] range of values, with highest values denoting highest acceptability [Chen S, et al. J Appl Clin Med Phys. 2019; 20(7):184-192]) in healthy volunteers.	At day 0
GROUP 2 - Multiparametric MRI acceptability in CKD patients.	Multiparametric MRI acceptability, in terms of comfort level and degree of satisfaction, assessed by a specific 9-item questionnaire ([9-45] range of values, with highest values denoting highest acceptability [Chen S, et al. J Appl Clin Med Phys. 2019; 20(7):184-192]) in CKD patients.	At day 0
GROUP 2 - within subject total kidney volume coefficient of variation after 1-2 weeks	Within subject coefficient of variation of measures computed by multiparametric renal MRI repeated after 1-2 weeks to assess total kidney volume reproducibility in CKD patients	At day 7-14
GROUP 2 - within subject renal artery blood flow coefficient of variation after 1-2 weeks	Within subject coefficient of variation of measures computed by multiparametric renal MRI repeated after 1-2 weeks to assess renal artery blood flow reproducibility in CKD patients	At day 7-14
GROUP 2 - within subject cortical perfusion coefficient of variation after 1-2 weeks	Within subject coefficient of variation of measures computed by multiparametric renal MRI repeated after 1-2 weeks to assess cortical perfusion reproducibility in CKD patients	At day 7-14
GROUP 2 - within subject cortical and medullary T1 coefficient of variation after 1-2 weeks	Within subject coefficient of variation of measures computed by multiparametric renal MRI repeated after 1-2 weeks to assess cortical and medullary T1 reproducibility in CKD patients	At day 7-14
GROUP 2 - within subject cortical and medullary T2 coefficient of variation after 1-2 weeks	Within subject coefficient of variation of measures computed by multiparametric renal MRI repeated after 1-2 weeks to assess cortical and medullary T2 reproducibility in CKD patients	At day 7-14
GROUP 2 - within subject cortical and medullary R2* coefficient of variation after 1-2 weeks	Within subject coefficient of variation of measures computed by multiparametric renal MR repeated after 1-2 weeks to assess cortical and medullary R2* reproducibility in CKD patients	At day 7-14
GROUP 2 - within subject cortical and medullary ADC coefficient of variation after 1-2 weeks	Within subject coefficient of variation of measures computed by multiparametric renal MRI repeated after 1-2 weeks to assess cortical and medullary ADC reproducibility in CKD patients	At day 7-14
GROUP 2 - Correlation coefficient between MRI-based parameters and eGFR	Assessment of the correlation coefficient between MRI-based parameters and eGFR to provide preliminary evidence of the nature and degree of change in multiparametric MRI measures across different stages of CKD	At day 0

Collaborators and Investigators

• Sponsor: Mario Negri Institute for Pharmacological Research
• Collaborators: Aarhus University Hospital; Heidelberg University; Clinica Universidad de Navarra, Universidad de Navarra
• Investigators: Study Chair: Giuseppe Remuzzi, MD, Istituto di Ricerche Farmacologiche Mario Negri IRCCS

Study record dates

Study Major Dates

• Study Start (Actual): November 25, 2022
• Primary Completion (Estimated): December 1, 2024
• Study Completion (Estimated): December 1, 2024

Study Registration Dates

• First Submitted: January 14, 2022
• First Submitted That Met QC Criteria: February 7, 2022
• First Posted (Actual): February 8, 2022

Study Record Updates

• Last Update Posted (Estimated): December 19, 2023
• Last Update Submitted That Met QC Criteria: December 18, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: Chronic kidney disease; Multiparametric MRI; Standardization; Clinical validity
• Additional Relevant MeSH Terms: Pathologic Processes; Urologic Diseases; Disease Attributes; Renal Insufficiency; Chronic Disease; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Kidney Diseases; Renal Insufficiency, Chronic
• Other Study ID Numbers: Respect

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No