Imaging Assessments of ARPKD Kidney Disease Progression

Recruiting

• Conditions: Autosomal Recessive Polycystic Kidney Disease

• Registration Number: NCT07201025
• Lead Sponsor: The Cleveland Clinic

Brief Summary

Autosomal Recessive Polycystic Kidney Disease (ARPKD) is a potentially lethal genetic disorder for which there are currently no disease specific treatments. Clinical trials have been limited by the absence of robust measures of disease progression. The overall goal of this 5 year NIH-funded prospective, observational multicenter study conducted at CC (primary site) and Children's Hospital of Philadelphia (CHOP) (collaborating site) is establish a set of rapid, quantitative, and reproducible novel kidney MRI measures applicable to standard clinical MRI scanners, which could serve as potential biomarkers to measure response to therapy in patients across the disease spectrum and all ages.

We will recruit a total of 45 ARPKD patients and 15 healthy controls at the the two sites . All subjects will be \> or = 6yrs old with no contraindications to undergoing MRI (non contrast). ARPKD subjects will be recruited into one of 3 cohorts based on their estimated glomerular filtration rate (eGFR): early CKD (eGFR\> or =90ml/min/1.73m2), mild CKD (60-89ml/min/1.73m2) and moderate CKD (30-59ml/min/1.73m2). For ARPKD subjects, participation will last 3 years and consist of a baseline and 3 subsequent annual visits. Healthy controls will only have 1 study visit. Study visits for all subjects will include collection of clinical and demographic data, clinical blood and urine tests (E.g. serum creatinine) and MRI imaging. ARPKD (but not healthy subjects) will also undergo a measured GFR test (iohexol clearance) to accurately assess their kidney function.

Detailed Description

Autosomal Recessive Polycystic Kidney Disease (ARPKD) is a potentially lethal genetic disorder that affects approximately 1/20,000 children and shares common cellular pathophysiology with other cystic kidney diseases, including Autosomal Dominant PKD (ADPKD). The genetics, pathology and clinical features of ARPKD, however, are distinct from ADPKD. In ARPKD, diffuse fusiform dilatations of the collecting tubules ("microcysts") predominate rather than the macrocysts seen in ADPKD. ARPKD kidneys may be very large at presentation, but, unlike ADPKD, actually stabilize in size as normal parenchyma is replaced by cysts and progressive fibrosis develops. ARPKD morbidity and mortality is significant: 30% of children die as neonates and 40-50% of survivors progress to end-stage kidney disease (ESKD) by age 18. Importantly, there are currently no disease-specific, clinically-available therapies for ARPKD and treatment is limited to chronic kidney disease (CKD) management. Several novel therapies have shown promise in ARPKD animal models. Unfortunately, there are currently no reliable clinical measures of ARPKD progression that show changes over a several year period of a clinical trial except in the most severely affected young children, creating a roadblock for implementing clinical trials for ARPKD therapies, especially in patients with less advanced disease.

Conventional endpoints for CKD progression, e.g., 50% decline in estimated glomerular filtration rate (eGFR) or progression to ESKD have substantial limitations in assessing ARPKD progression. Studies from 2 prospective observational cohorts found that the rates of GFR decline in ARPKD patients was relatively slow but also highly variable. Magnetic Resonance Imaging (MRI) measures of total kidney volume (TKV), which have been used successfully in ADPKD trials, are generally not applicable to ARPKD, since TKV does not increase with progressive disease except in severely affected young patients. Therefore, there is a critical need for new, sensitive biomarkers to enable effective clinical trials of therapies for ARPKD. Quantitative MRI techniques, including novel Magnetic Resonance Fingerprinting (MRF), Arterial Spin Labelling (ASL) and Magnetic Resonance Elastography (MRE), have the potential to provide measurable assessments of kidney structure and function. The overall objective of this multi-site study is to establish a set of rapid, quantitative, and reproducible kidney MRI methods applicable to standard clinical MRI scanners, which could serve as potential biomarkers to risk stratify ARPKD patients for clinical trial enrollment and measure response to therapy across the kidney disease spectrum and all ages.

The Aims of this study are 1) to determine the capability of our multimodal MRI biomarkers to accurately and repeatably detect and stage ARPKD kidney disease across the full spectrum of disease from early-stage CKD characterized by diffuse kidney cysts (MRF) and reduced kidney perfusion (ASL) to later-stage CKD characterized by progressive kidney fibrosis (MR elastography, MRE); (2) determine the sensitivity of these MRI biomarkers to detect changes in ARPKD kidney disease progression over time in comparison to gold-standard GFR assessments; and (3) determine the feasibility of a new free-breathing MRF methodology that would allow infants and young children to be scanned without sedation. For these studies, we will recruit ARPKD patients ≥6 years of age with early, mild, and moderate CKD from across the US for 4 annual multimodal MRI scans and GFR measurements at our two collaborating sites (CC/CWRU and CHOP). Age-matched healthy controls will also be recruited for an MRI scan. If successful, the proposed studies will support use of these multimodal MRI biomarkers as outcome measures and/or high-risk subject enrichment for future clinical trials for ARPKD patients.

Study Timeline

• Study Start: 2024-12-12
• Status Verified: 2025-09
• Study First Submitted: 2025-09-23
• Study First Submitted QC: 2025-09-23
• Last Update Submitted: 2025-09-23
• Study First Posted: 2025-10-01
• Last Update Posted: 2025-10-01
• Primary Completion: 2029-02-28
• Study Completion: 2029-02-28

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 60

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
The diagnostic performance (AUROC, sensitivity, specificity) of the multimodal MRI assessments MRF (mean kidney T1 and T2), ASL (mean kidney perfusion), and MRE (mean kidney stiffness), alone or in combination to differentiate the 4 study cohorts	3 Years
The relationship between the imaging biomarkers, MRF (mean kidney T1 and T2), ASL (mean kidney perfusion), and MRE (mean kidney stiffness) alone or in combination, to baseline and change in measured GFR over 3 years in the 3 ARPKD cohorts	3 Years
The level of agreement between breath-hold and free breathing kidney MRF assessments in the 4 cohorts	3 Years

Secondary Outcome Measures

Name	Time	Method
Repeatability of multimodal MRI assessments in ARPKD and healthy control subjects	3 years
Reproducibility of findings at the two study sites	3 Years

Trial Locations

Locations (2)

Cleveland Clinic; 🇺🇸 Cleveland, Ohio, United States

Children's Hospital of Philadelphia; 🇺🇸 Philadelphia, Pennsylvania, United States