Biomarkers of Lichen Sclerosus

Discovery and Validation of Biomarkers of Lichen Sclerosus

Lichen sclerosus (LS) is a skin condition of the external genitals (vulva) of women. LS causes vulvar itching, pain, and burning. In addition, LS causes scarring of the vulva which may cause significant lack of sexual pleasure or pain. Lastly, 4-6% of women with LS will develop vulvar cancer. The purpose of this study is to learn the gene expression file changes in skins affected by LS as compared to normal skins in order to discover the mechanism of the LS, and further to develop effective drugs to treat the condition.

Study Overview

• Status: Unknown
• Conditions: Lichen Sclerosus

Detailed Description

Lichen sclerosus (LS) is a chronic, lymphocyte mediated cutaneous disorder affecting approximately one in seventy women. Presenting symptoms may include intense pruritis, pain, burning, and dyspareunia. This disorder may affect any area of the skin, but has a notable predilection for the female genital region, in particular, the vulva, per anal area and the groin. Affected females outnumber affected males by 13:1. Typically, the patient is a menopausal woman, but prepubertal girls and women of all ages may be affected. The typical lesions of lichen sclerosus are white plaques and papules, often with areas of ecchymosis, excoriation, and ulceration. Often, there is destruction of the vulvar architecture with scarring of the clitoral prepuce, resorption of the labia minora, and narrowing of the introitus. Vulvar lichen sclerosus has a 4%-6% transformation malignant rate and women with the disease are at a 250-fold increased risk for developing vulvar carcinoma than women without lichen sclerosus. While the exact etiology of LS is as yet unknown, there is at least a suggested genetic component as evidenced by case reports of familial LS, findings of associations with HLA antigens, and high rates of concordance with other autoimmune disorder.

The purpose of this study is to determine the differences in the genomic/proteomic profiles between LS and normal skin biopsies for women with active vulvar lichen sclerosus in order to identify potential biomarkers that can be used for the prevention, early diagnosis and effective treatment for LS. The study will aim to identify genes/proteins/glycoproteins biomarkers that are associated with LS, select biomarkers associated with LS either individual candidate biomarker or as a panel, validate the identified candidate biomarkers for LS using targeted analysis of candidate biomarkers from independent LS specimen sets, develop assays to determine the clinical utilities of the identified biomarkers as minimum invasive tests for the early detection of LS and determine the clinical utility of biomarkers for biopsy-based tissue tests for LS diagnosis and treatment.

• Study Type: Observational
• Enrollment (Anticipated): 58

Contacts and Locations

• Study Contact: Name: Andrew T Goldstein, MD; Phone Number: 4102790209; Email: obstetrics@yahoo.com
• Study Contact Backup: Name: Charles Marci, MD; Phone Number: 202-741-2510

Study Locations

• United States
  • District of Columbia
    • Washington, District of Columbia, United States, 20037
      • Recruiting
      • The Centers For Vulvovaginal Disorders
      • Contact: Andrew T Goldstein, MD; Phone Number: 202-887-0568; Email: drg.cvvd@gmail.com
      • Contact: Leia Mitchell, MD; Phone Number: (202)887-0568; Email: drg.cvvd@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 73 years (Adult, Older Adult)
• Accepts Healthy Volunteers: N/A
• Genders Eligible for Study: Female

• Sampling Method: Non-Probability Sample

Study Population

The total number of subjects to expected to be recruited are 58 total.

• six families with 2-3 family members affected in each family with LS
• 40 patients (sporadic) with active lichen sclerosus

Description

Inclusion Criteria:

• 18-75 of age
• Diagnosis of active, Histologically proven, vulvar lichen sclerosus

Exclusion Criteria:

• Under the age of 18 or over the age of 75.
• Participants who are pregnant at the time of recruitment

• If, in the clinical opinion of Dr. Andrew Goldstein, she:

  • does not have active LS
  • has active infection
  • has evidence of any other dermatologic disease of the vulva
  • has evidence of neoplastic disease of the vulva
• If, in the opinion of Dr. Andrew Goldstein, they will be unable to keep the biopsy sites clean until they heal.
• If the biopsy specimen sent to dermatopathology is not confirmatory for active lichen sclerosus then the specimens obtained from that patient will be excluded from the study.

Study Plan

How is the study designed?

Design Details

• Observational Models: Other
• Time Perspectives: Cross-Sectional

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Differential gene expression between LS and normal vulvar skin tissue	Gene expression obtained from biopsies via Next Generation Sequencing (RNASeq)	1-2 year
Differential protein expression between LS and normal vulvar skin tissue	Protein expression obtained from biopsies via Western blot	1-2 year
Identification of tissue-derived glycoproteins in serum	Glycoproteins identified via glycoproteomic technologies	1-2 years

Collaborators and Investigators

• Sponsor: Center for Vulvovaginal Disorders
• Collaborators: George Washington University; Gynecologic Cancer Research Foundation
• Investigators: Principal Investigator: Andrew T Goldstein, MD, The Center for Vulvovaginal Disorders; Principal Investigator: Charles Macri, MD, George Washington University School of Medicine and Health Sciences; Principal Investigator: Sidney Fu, MD, PhD, George Washington University School of Medicine and Health Sciences

Publications and helpful links

Helpful Links

• Informed Consent

Study record dates

Study Major Dates

• Study Start (Actual): November 27, 2017
• Primary Completion (Anticipated): November 26, 2019
• Study Completion (Anticipated): November 26, 2019

Study Registration Dates

• First Submitted: January 2, 2018
• First Submitted That Met QC Criteria: June 17, 2018
• First Posted (Actual): June 19, 2018

Study Record Updates

• Last Update Posted (Actual): June 19, 2018
• Last Update Submitted That Met QC Criteria: June 17, 2018
• Last Verified: June 1, 2018

More Information

Terms related to this study

• Keywords: lichen sclerosus
• Additional Relevant MeSH Terms: Skin Diseases; Skin Diseases, Papulosquamous; Lichenoid Eruptions; Lichen Sclerosus et Atrophicus
• Other Study ID Numbers: 091739

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: The data will be summarized in publication and presentation. Individual results will not be communicated, and nor the study participants will be contacted about their results.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No