Nephrogenic Systemic Fibrosis (NSF): Analysis of Tissue Gadolinium Levels

NCT01014754 | Completed DMC

• 2 other identifiers: STU1460NIH Grant #2 R01 CA102713-03A2
• Study Type: observational
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

The primary objective of this study is to determine any causative or associated factors for the development of Nephrogenic Systemic Fibrosis (NSF), Nephrogenic Fibrosing Dermopathy (NFD), or related diagnosis. Our primary focus will be on the previous administration of gadolinium to these patients, but we will also look at other postulated causes and risk factors. The secondary objective of this study is to assess tissue gadolinium (Gd) levels in five groups of subjects:

• Those affected by NSF.
• Those with normal kidney function who have undergone a medical imaging procedure using Gd-based contrast agent (GBCA) in the 2 years prior to a skin biopsy.
• Those with normal kidney function who have never been exposed to GBCA and have had a skin biopsy.
• Those on dialysis or with eGFR ≤ 30 ml/min/1.73 m2 who have had a medical imaging procedure using GBCA in the 2 years prior to skin biopsy.
• Those on dialysis or with eGFR ≤ 30 ml/min/1.73 m2 who have never been exposed to GBCA and have had skin biopsy. We hypothesize that there is a correlation between the administration of Gd-containing agents usually associated with MRI procedures and the development of NSF in those with renal failure and some other predisposing condition. We also hypothesize that tissue Gd levels in those with NSF will be higher than in those who have been exposed to GBCA but do not have NSF. Of the two groups without NSF but with exposure to GBCA, we hypothesize that those with kidney dysfunction will have higher tissue Gd levels than those with normal kidney function. We hypothesize that in the two groups of subjects without exposure to GBCA, there will be no detectable levels of Gd, regardless of kidney function status.

Conditions

Nephrogenic Systemic Fibrosis; Nephrogenic Fibrosing Dermopathy

Outcome Measures

Primary Outcomes (1)

• To determine causative or associated factors for the development of Nephrogenic Systemic Fibrosis (NSF), Nephrogenic Fibrosing Dermopathy (NFD), or related diagnosis.

  1988 to present

Secondary Outcomes (1)

• Tissue Gadolinium Level in 5 groups of patients, with and without NSF

  1988 to present

Study Arms (6)

NSF

Biopsy-proven diagnosis of NSF

Kidney dysfunction plus gadolinium exposure

Those on dialysis or with eGFR ≤ 30 ml/min/1.73 m2 who have had a medical imaging procedure using GBCA in the 2 years prior to skin biopsy.

Kidney dysfunction without gadolinium exposure

Those on dialysis or with eGFR ≤ 30 ml/min/1.73 m2 who have never been exposed to GBCA and have had skin biopsy.

Normal kidney function with gadolinium exposure

Those with normal kidney function who have undergone a medical imaging procedure using Gd-based contrast agent (GBCA) in the 2 years prior to a skin biopsy.

Normal kidneys without gadolinium exposure

Those with normal kidney function who have never been exposed to GBCA and have had a skin biopsy.

Controls

Existing skin tissue from neonatal skin (\<6 months) will be used as controls, as they presumably have never been exposed to gadolinium

Eligibility Criteria

• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Those with NSF (25). 40 subjects selected through Northwestern University Department of Dermatology's existing medical records and pathology specimens. Medical records will be reviewed to identify 10 subjects who have had a standard of care skin biopsy in the dermatology clinics at Northwestern University and who were exposed to Gadolinium in the 2 years prior to skin biopsy. Another 10 subjects who have had skin biopsy and who have never been exposed to GBCA during a medical imaging procedure will also be identified. Another 10 subjects on dialysis or with eGFR ≤30 exposed to GBCA in the 2 years prior to skin biopsy will be identified. Another group of 10 subjects on dialysis or with eGFR ≤30 who have had skin biopsy and who have never been exposed to GBCA during a medical imaging procedure will also be identified. Neonatal skin tissue of up to 10 subjects with existing skin tissue sample will be sent for analysis.

You may qualify if:

• Biopsy-confirmed diagnosis of NSF

You may not qualify if:

• Does not have NSF
• Normal renal plus gadolinium exposure
• eGFR \>30
• Existing skin tissue sample
• Gadolinium exposure in 2 years preceding skin biopsy
• Abnormal renal plus gadolinium exposure
• eGFR \<30 or on dialysis
• Existing skin tissue sample
• Gadolinium exposure in 2 years preceding skin biopsy
• Abnormal renal without gadolinium exposure
• eGFR \<30 or on dialysis
• Existing skin tissue sample
• No gadolinium exposure ever
• Normal renal without gadolinium exposure
• eGFR \>30

Sponsors & Collaborators

• Northwestern University: lead
• National Institutes of Health (NIH): collaborator

Study Sites (1)

Northwestern University Feinberg School of Medicine, Department of Dermatology

Chicago, Illinois, 60611, United States

Location

Related Publications (3)

• High WA, Ayers RA, Chandler J, Zito G, Cowper SE. Gadolinium is detectable within the tissue of patients with nephrogenic systemic fibrosis. J Am Acad Dermatol. 2007 Jan;56(1):21-6. doi: 10.1016/j.jaad.2006.10.047. Epub 2006 Nov 9.

  PMID: 17097388 BACKGROUND

• Khurana A, Greene JF Jr, High WA. Quantification of gadolinium in nephrogenic systemic fibrosis: re-examination of a reported cohort with analysis of clinical factors. J Am Acad Dermatol. 2008 Aug;59(2):218-24. doi: 10.1016/j.jaad.2008.04.010. Epub 2008 Jun 5.

  PMID: 18538448 BACKGROUND

• Cowper SE, Robin HS, Steinberg SM, Su LD, Gupta S, LeBoit PE. Scleromyxoedema-like cutaneous diseases in renal-dialysis patients. Lancet. 2000 Sep 16;356(9234):1000-1. doi: 10.1016/S0140-6736(00)02694-5.

  PMID: 11041404 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Existing skin tissue from standard of care biopsies

MeSH Terms

Conditions

Nephrogenic Fibrosing Dermopathy

Condition Hierarchy (Ancestors)

Skin Diseases; Skin and Connective Tissue Diseases; Fibrosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Anne Laumann, MBChB, MRCP(UK)

  Northwestern University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Dermatology

Study Record Dates

• First Submitted: November 13, 2009
• First Posted: November 17, 2009
• Study Start: August 1, 2007
• Primary Completion: April 1, 2014
• Study Completion: June 1, 2014
• Last Updated: December 4, 2014

Record last verified: 2014-12

Locations

US (1)