Role of Nox2 in CNI-induced Renal Fibrosis

NCT01674465 | Completed DMC

• 5 other identifiers: 2016-0384R01DK0924542011-0127A534280SMPH/MEDICINE/MEDICINE*N
• Study Type: observational
• Target: 8
• Locations: 1 country
• Sites: 2

Brief Summary

Calcineurin Inhibitors (CNI) are drugs used to suppress the immune system when a person has a solid organ transplant. Although these drugs keep the transplanted organ from being rejected they are toxic to kidneys, or nephrotoxic. CNIs cause damage, called fibrosis, to kidneys. Fibrosis is a type of scarring that occurs in kidney tissue. Fibrosis can eventually lead to kidney failure. One of the pathways that cause fibrosis is a chronic lack of oxygen to the kidney tissue called "hypoxia". There is a protein called Nox2 that may be involved in how this hypoxia happens in the kidney. The Department of Medicine-Nephrology at the University of Wisconsin is conducting a research study to see how much of the Nox2 protein is present in kidneys that may have fibrosis caused by CNIs and whether a certain type of Magnetic Resonance Imaging (MRI) can be used to tell in advance if the disease caused by CNIs is getting worse. Study hypothesis: MRI, a non-invasive technique, can be used to determine whether CNI induced kidney disease is getting worse. Additionally, the study aims to determine the role of Nox2 in CNI nephrotoxicity.

Conditions

Kidney Disease

Keywords

Kidney fibrosis; Kidney hypoxia; Calcineurin inhibitors

Outcome Measures

Primary Outcomes (1)

• Nox2 presence in CNI nephrotoxic kidneys

  The Nox2 protein will be determined in subjects who are potentially have CNI nephrotoxicity

  two hours post Hypoxyprobe-1 Infusion

Secondary Outcomes (1)

• Oxygenation changes in kidneys using BOLD-MRI.

  12 months

Study Arms (1)

CNI-induced nephrotoxicity

Hypoxyprobe-1

Biological: Hypoxyprobe-1

Interventions

Hypoxyprobe-1 BIOLOGICAL

Hypoxyprobe-1 is a biological marker used to detect oxygen levels in tissue;subjects will receive and intravenous solution for 20 minutes containing 500mg/m\^2 two-three hours prior to their standard of care biopsy

Also known as: Pimonidazole

CNI-induced nephrotoxicity

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Study population will be chosen from non-kidney transplant patients scheduled for a standard of care kidney biopsy.

You may qualify if:

• liver, heart, lung or pancreas transplant recipients
• suspected CNI induced nephrotoxicity

You may not qualify if:

• minors
• pregnant women
• prisoners
• institutionalized individuals or other vulnerable groups
• history of allergic reactions or adverse reactions to Pimonidazole
• Claustrophobia
• hazardous metallic implants
• cardiac pacemakers

Sponsors & Collaborators

• University of Wisconsin, Madison: lead

Study Sites (2)

Wisconsin Institute for Medical Research (WIMR)

Madison, Wisconsin, 53705, United States

Location

University of Wisconsin Hospital and Clinics

Madison, Wisconsin, 53792, United States

Location

MeSH Terms

Conditions

Kidney Diseases

Interventions

pimonidazole

Condition Hierarchy (Ancestors)

Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Study Officials

• Arjang Djamali, MD,MS,FASN

  University of Wisconsin-Madison, School of Medicine and Public Health, Department of Medicine, Division of Nephrology

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 3, 2012
• First Posted: August 28, 2012
• Study Start: November 30, 2012
• Primary Completion: August 9, 2018
• Study Completion: October 10, 2019
• Last Updated: October 14, 2019

Record last verified: 2019-10

Locations

US (2)