Skin Biopsy Specimens as Biomarkers of Systemic Sclerosis and Response to Mycophenolate Mofetil

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00853788
Recruitment Status : Completed
First Posted : March 2, 2009
Last Update Posted : February 17, 2012
Dartmouth-Hitchcock Medical Center
Information provided by (Responsible Party):
Monique Hinchcliff, Northwestern University

Brief Summary:
The purpose of this study is to assess whether skin biopsy specimens from patients with diffuse cutaneous systemic sclerosis (dcSSc) can be used as biomarkers (measures of activity and type) of disease to predict response to various experimental treatments. There are various experimental treatments being used in the treatment of slceroderma, but there is no way to predict response to any given therapy. The investigators will use DNA microarray to analyze the changes in gene expression in skin biopsies in response to various treatments. Our hypothesis is that the investigators will see changes in gene expression in response to various treatments that will give us insight into the cause of scleroderma. The investigators predict that they will be able to use this information to predict which experimental treatments will be beneficial to individual patients

Condition or disease
Systemic Sclerosis

Detailed Description:

Systemic sclerosis (SSc) is an autoimmune connective tissue disease primarily affecting young to middle-aged women. The pathogenesis of SSc is complex involving interplay of three seemingly diverse processes: autoimmunity, vasculopathy, and fibrosis. Patients experience varying degrees of disabling skin thickening and potentially life-threatening internal organ fibrosis and vasculopathy, but there is no way to accurately predict disease subtype and risk for severity and progression. Current experimental treatments for SSc include oral and intravenous cyclophosphamide and mycophenolate mofetil that blunt the immune response, autologous stem cell transplant that may reset the immune system, and imatinib mesylate that may reduce fibrosis.

Recent exciting genomics research from our lab and our collaborator suggests that skin biopsy samples obtained from patients with SSc have robust alterations in gene expression profiles compared to controls. Changes in expression of genes known to be involved in profibrotic pathways were prominent. The present proposal describes novel experiments to evaluate genomic approaches coupled with clinical data to identify patient subsets, predict response to treatment, and to better understand the molecular basis for disease pathogenesis, and treatment response.

The Northwestern Scleroderma Program (NSP) is a novel multidisciplinary program to accelerate SSc research and provide comprehensive care to >400 SSc patients. Standardized clinical information including demographic, laboratory, and diagnostic data (echocardiography, high resolution chest computerized tomography, and pulmonary function testing) as well as DNA is currently collected on all patients and entered into a clinical database. NSP patients will be offered the option to donate dermal tissue for genomic analysis using a previously established, optimized approach to extract RNA from tissue samples.

We hypothesize that our DNA microarray technique will permit analysis of changes in gene expression from the skin of patients undergoing dermal biopsies before and after treatment and will identify unrecognized profibrotic pathways in addition to providing new, important information regarding known fibrotic pathways. The knowledge gained will not only deepen our understanding of the molecular pathways involved in fibrosis, but also provide a means to reliably predict which patients are likely to respond to various treatments.


SSc is a devastating orphan connective tissue disease with no known cure. There are no disease biomarkers that can accurately predict disease subtype or risk for internal organ involvement and progression at present. Using well-established genomic techniques, the current proposal will investigate if changes in gene expression of profibrotic pathways in dermal biopsies before and after various treatments correlates with clinical response. If so, genonic analysis of dermal tissue may be useful to better understand the molecular pathogenesis of SSc and as a disease biomarker.

Study Type : Observational
Actual Enrollment : 40 participants
Observational Model: Case Control
Time Perspective: Prospective
Official Title: Genomic and Histological Analysis of Skin Biopsy Specimens as Biomarkers of Systemic Sclerosis and Response to Mycophenolate Mofetil
Study Start Date : November 2008
Actual Primary Completion Date : June 2011
Actual Study Completion Date : June 2011

Biospecimen Retention:   Samples Without DNA
skin biopsy samples

Information from the National Library of Medicine

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Ages Eligible for Study:   19 Years to 90 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
patients with diffuse cutaneous systemic sclerosis

Inclusion Criteria:

  • 18 years of age
  • systemic sclerosis

Exclusion Criteria:

  • pregnant
  • bleeding disorder
  • history of delayed wound healing

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00853788

United States, Illinois
Northwestern Memorial Faculty Foundation
Chicago, Illinois, United States, 60611
Sponsors and Collaborators
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Dartmouth-Hitchcock Medical Center
Principal Investigator: Monique Hinchcliff, MD Northwestern University

Responsible Party: Monique Hinchcliff, Monique Hinchcliff, MD, MS, Northwestern University Identifier: NCT00853788     History of Changes
Other Study ID Numbers: STU00004428
5K12HD055884-02 ( U.S. NIH Grant/Contract )
First Posted: March 2, 2009    Key Record Dates
Last Update Posted: February 17, 2012
Last Verified: February 2012

Keywords provided by Monique Hinchcliff, Northwestern University:
systemic sclerosis

Additional relevant MeSH terms:
Scleroderma, Systemic
Scleroderma, Diffuse
Pathologic Processes
Connective Tissue Diseases
Skin Diseases
Mycophenolic Acid
Antibiotics, Antineoplastic
Antineoplastic Agents
Antibiotics, Antitubercular
Antitubercular Agents
Anti-Bacterial Agents
Anti-Infective Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action