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

This study is enrolling participants by invitation only.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Anne Laumann, Northwestern University
ClinicalTrials.gov Identifier:
NCT01014754
First received: November 13, 2009
Last updated: April 21, 2013
Last verified: April 2013
  Purpose

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.


Condition
Nephrogenic Systemic Fibrosis
Nephrogenic Fibrosing Dermopathy

Study Type: Observational
Study Design: Observational Model: Case Control
Official Title: Nephrogenic Systemic Fibrosis and Gadolinium—A Medical Record Review With Analysis of Existing Skin and Other Tissue Specimens to Assess Potential Causative or Associated Factors

Resource links provided by NLM:


Further study details as provided by Northwestern University:

Primary Outcome Measures:
  • To determine causative or associated factors for the development of Nephrogenic Systemic Fibrosis (NSF), Nephrogenic Fibrosing Dermopathy (NFD), or related diagnosis. [ Time Frame: 1988 to present ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Tissue Gadolinium Level in 5 groups of patients, with and without NSF [ Time Frame: 1988 to present ] [ Designated as safety issue: No ]
    • 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.


Biospecimen Retention:   Samples With DNA

Existing skin tissue from standard of care biopsies


Estimated Enrollment: 75
Study Start Date: August 2007
Estimated Study Completion Date: April 2014
Estimated Primary Completion Date: April 2014 (Final data collection date for primary outcome measure)
Groups/Cohorts
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

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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.

Criteria

NSF group

Inclusion Criteria:

  • Biopsy-confirmed diagnosis of NSF

Exclusion Criteria:

  • Does not have NSF

Normal renal plus gadolinium exposure

Inclusion Criteria:

  • eGFR >30
  • Existing skin tissue sample
  • Gadolinium exposure in 2 years preceding skin biopsy

Exclusion Criteria:

  • Does not fit inclusion criteria

Abnormal renal plus gadolinium exposure

Inclusion Criteria:

  • eGFR <30 or on dialysis
  • Existing skin tissue sample
  • Gadolinium exposure in 2 years preceding skin biopsy

Exclusion Criteria:

  • Does not fit inclusion criteria

Abnormal renal without gadolinium exposure

Inclusion Criteria:

  • eGFR <30 or on dialysis
  • Existing skin tissue sample
  • No gadolinium exposure ever

Exclusion Criteria:

  • Does not fit inclusion criteria

Normal renal without gadolinium exposure

Inclusion Criteria:

  • eGFR >30
  • Existing skin tissue sample
  • No gadolinium exposure ever

Exclusion Criteria:

  • Does not fit inclusion criteria

Controls (neonatal)

Inclusion Criteria:

  • Existing skin biopsy tissue that was performed within the first 6 months of life

Exclusion criteria:

  • Does not fit inclusion criteria
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01014754

Locations
United States, Illinois
Northwestern University Feinberg School of Medicine, Department of Dermatology
Chicago, Illinois, United States, 60611
Sponsors and Collaborators
Northwestern University
Investigators
Principal Investigator: Anne Laumann, MBChB, MRCP(UK) Northwestern University
  More Information

Publications:
Responsible Party: Anne Laumann, Professor of Dermatology, Northwestern University
ClinicalTrials.gov Identifier: NCT01014754     History of Changes
Other Study ID Numbers: STU1460, NIH Grant #2 R01 CA102713-03A2
Study First Received: November 13, 2009
Last Updated: April 21, 2013
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Fibrosis
Nephrogenic Fibrosing Dermopathy
Pathologic Processes
Skin Diseases

ClinicalTrials.gov processed this record on July 24, 2014