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

This study has been completed.
Sponsor:
Collaborator:
Dartmouth-Hitchcock Medical Center
Information provided by (Responsible Party):
Monique Hinchcliff, Northwestern University
ClinicalTrials.gov Identifier:
NCT00853788
First received: February 26, 2009
Last updated: February 15, 2012
Last verified: February 2012
  Purpose

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
Systemic Sclerosis

Study Type: Observational
Study Design: 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

Resource links provided by NLM:


Further study details as provided by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD):

Biospecimen Retention:   Samples Without DNA

skin biopsy samples


Enrollment: 40
Study Start Date: November 2008
Study Completion Date: June 2011
Primary Completion Date: June 2011 (Final data collection date for primary outcome measure)
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.

Relevance:

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.

  Eligibility

Ages Eligible for Study:   19 Years to 90 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

patients with diffuse cutaneous systemic sclerosis

Criteria

Inclusion Criteria:

  • 18 years of age
  • systemic sclerosis

Exclusion Criteria:

  • pregnant
  • bleeding disorder
  • history of delayed wound healing
  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: NCT00853788

Locations
United States, Illinois
Northwestern Memorial Faculty Foundation
Chicago, Illinois, United States, 60611
Sponsors and Collaborators
Dartmouth-Hitchcock Medical Center
Investigators
Principal Investigator: Monique Hinchcliff, MD Northwestern University
  More Information

No publications provided

Responsible Party: Monique Hinchcliff, Monique Hinchcliff, MD, MS, Northwestern University
ClinicalTrials.gov Identifier: NCT00853788     History of Changes
Other Study ID Numbers: STU00004428, 5 K12 HD055884-02
Study First Received: February 26, 2009
Last Updated: February 15, 2012
Health Authority: United States: Federal Government

Keywords provided by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD):
systemic sclerosis
biomarkers
microarray

Additional relevant MeSH terms:
Scleroderma, Systemic
Scleroderma, Diffuse
Sclerosis
Connective Tissue Diseases
Skin Diseases
Pathologic Processes
Mycophenolate mofetil
Mycophenolic Acid
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on August 18, 2014