Dynamic Imaging of Variation in Lupus Nephritis (DIVINE)

• ClinicalTrials.gov Identifier: NCT03180021
• Recruitment Status: Completed
• First Posted: June 7, 2017
• Last Update Posted: October 4, 2021
• Sponsor: RILITE Foundation
• Information provided by (Responsible Party): RILITE Foundation

Study Description

Brief Summary:

To use a variety of renal imaging modalities, including diffusion weighted imaging (DWI), blood oxygen level dependent (BOLD) imaging, T1rho (T1rho) imaging, and dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) to evaluate the intra-renal blood flow, perfusion, cellularity, fibrosis and atrophy within the kidneys of patients with lupus nephritis (LN) and compare these parameters to renal biopsy findings to determine whether DWI, BOLD, T1rho, and DCE-MRI may provide a set of non-invasive tools to assess renal function and pathology in LN.

Condition or disease	Intervention/treatment
Lupus Nephritis	Procedure: MRI

Study Design

• Study Type: Observational
• Actual Enrollment: 21 participants
• Observational Model: Case-Control
• Time Perspective: Prospective
• Official Title: Dynamic Imaging of Variation in Lupus Nephritis
• Actual Study Start Date: March 13, 2018
• Actual Primary Completion Date: September 25, 2020
• Actual Study Completion Date: October 2, 2020

Groups and Cohorts

Group/Cohort	Intervention/treatment
Patients with Lupus Nephritis	Procedure: MRI; This is a multicenter, non-interventional, pilot study. Eligible subjects will have a baseline MRI of the kidney, including anatomical, DWI, BOLD, T1rho, and DCE-MRI, utilizing a macrocyclic gadolinium-based contrast agent (GBCA), followed by planned standard of care (SOC) renal biopsy and clinical laboratory assessments. Additional serum and urine will be collected from subjects at baseline for analysis of research biomarkers. Following the results of the biopsy and clinical laboratory assessments, subjects will be treated for their underlying disease at the discretion of the investigator. At 6 months, subjects will return to the clinic for a second MRI, SOC clinical and laboratory evaluation and collection of serum and urine for analysis of research biomarkers.
Patients with IgA Neuropathy	Procedure: MRI; This is a multicenter, non-interventional, pilot study. Eligible subjects will have a baseline MRI of the kidney, including anatomical, DWI, BOLD, T1rho, and DCE-MRI, utilizing a macrocyclic gadolinium-based contrast agent (GBCA), followed by planned standard of care (SOC) renal biopsy and clinical laboratory assessments. Additional serum and urine will be collected from subjects at baseline for analysis of research biomarkers. Following the results of the biopsy and clinical laboratory assessments, subjects will be treated for their underlying disease at the discretion of the investigator. At 6 months, subjects will return to the clinic for a second MRI, SOC clinical and laboratory evaluation and collection of serum and urine for analysis of research biomarkers.

Outcome Measures

Primary Outcome Measures :

1. Diffusion Weight Imaging [ Time Frame: 7 Months ]
   Diffusion weighted imaging (DWI) measures ADC values that quantify the combined effects of blood microcirculation and Brownian motion of water molecules within the interstitial space.
2. Blood Oxygen Level Dependent Imaging [ Time Frame: 7 Months ]
   Blood oxygen level dependent (BOLD) imaging has been widely used to analyze blood flow in various 15 and is the preferred method to detect regional differences in blood flow.
3. T1rho Imaging [ Time Frame: 7 Months ]
   T1rho (T1rho) imaging is an MRI technique that is sensitive to the presence of macromolecules, such as collagen and proteoglycan 13.
4. Dynamic Contrast Enhanced Magnetic Resonance Imaging [ Time Frame: 7 Months ]
   Dynamic contrast enhanced (DCE) MRI (DCE-MRI) is an imaging method where T1-weighted MRI scans are acquired dynamically after injection of an MRI contrast agent (e.g., macrocylic gadolinium).

Biospecimen Retention:   Samples With DNA

To collect blood and urine samples for future research to identify biomarkers specific to systemic lupus erythematosus and to LN.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No
• Sampling Method: Non-Probability Sample

Study Population

Patients with Lupus Nephritis or IgA neuropathy selected at academic sites listed.

Criteria

Inclusion Criteria:

1. Provide written informed consent agreeing to all study procedures, before any study- specific procedures are done.
2. Male and female subjects 18 to 65 years of age, inclusive.
3. Subjects currently being evaluated for new or recurrent LN with a SOC kidney biopsy planned OR being evaluated for IgA nephropathy and with a SOC kidney biopsy planned.
4. Patients with LN must meet American College of Rheumatology (ACR) or Systemic Lupus Collaborating Clinics (SLICC) criteria for Systemic Lupus Erythematosus (SLE).
5. Subjects with a life expectancy >6 months.

Exclusion Criteria:

1. Participation in another investigational study during same time period.
2. Contraindication to receiving a GBCA.
3. More than 2 previous lifetime exposures to a GBCA.
4. Any contraindication to MRI, including metal implants, claustrophobia or morbid obesity.
5. Acute or chronic severe renal insufficiency (glomerular filtration rate [GFR] <40 mL per minute per 1.73 m2).
6. Subject requiring dialysis.
7. Presence of pre-existing renal disease unrelated to SLE or IgA nephropathy, respectively.
8. Acute renal insufficiency of any severity caused by the hepato-renal syndrome.
9. Previous or pre-existing nephrogenic systemic fibrosis.
10. History of clinically significant anti-phospholipid syndrome.
11. Chronic liver function impairment, indicated by liver function tests (aspartate aminotransferase [AST], alanine aminotransferase [ALT]) >2-fold upper limit of normal.
12. Platelet count <50,000/μL.
13. Hemoglobin <8.0 g/dL.
14. History of or presence of central nervous system (CNS) disease such as active lupus cerebritis or multiple sclerosis that might compromise blood brain barrier function.
15. Infection that is clinically relevant, particularly hepatitis B virus (HBV), hepatitis C virus (HCV) and/or human immunodeficiency virus (HIV).
16. Pregnant or nursing females, or females not using effective contraception.
17. Inability or unwillingness to return to the research site clinic for study visits at baseline and at 6 months.

Contacts and Locations

Locations

United States, Colorado

The Regents of the University of Colorado

Aurora, Colorado, United States, 80045

United States, New York

New York University School of Medicine

New York, New York, United States, 10002

The Trustees of Columbia University in the City of New York

New York, New York, United States, 10032

United States, Ohio

Ohio State University

Columbus, Ohio, United States, 43210

United States, South Carolina

Medical University of South Carolina

Charleston, South Carolina, United States, 29425

United States, Texas

University of Texas Southwestern Medical Center

Dallas, Texas, United States, 75390

Sponsors and Collaborators

RILITE Foundation

More Information

• Responsible Party: RILITE Foundation
• ClinicalTrials.gov Identifier: NCT03180021
• Other Study ID Numbers: RIL-001
• First Posted: June 7, 2017
• Last Update Posted: October 4, 2021
• Last Verified: October 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Nephritis; Lupus Nephritis; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Glomerulonephritis; Lupus Erythematosus, Systemic; Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases