Multicenter Phenotype-Genotype Analysis of Vascular Stains to Optimize Treatment Utilizing Optical Coherence Tomography
a study on Vascular Stains
The purpose of this research study is to develop a better understanding of vascular stains and to improve the usual laser treatment for vascular stain by using optical coherence tomography (OCT). This study is being done at the University of Wisconsin-Madison (UW-Madison) and University of California, Irvine. A total of about 85 people will participate in this study.
Vascular stains, commonly called "port wine birthmarks," are vascular anomalies that affect 0.3-0.5% of newborns; they impact quality of life due to soft tissue overgrowth, nodularity and life-altering, stigmatizing disfigurement. Laser treatment is the standard of care and relies on photocoagulation of vessels. Yet less than 25% are reported to clear entirely; the reason for this lack of response is poorly understood. Recently, mosaic mutations in genes that control cell-cycle regulation including GNAQ, GNA11, PiK3CA and others were elucidated as a genetic cause for these birthmarks. This finding has transformed our fundamental understanding of their pathophysiology. It provides a molecular explanation for laser resistance, as these genes share oncogenic pathways that result in synchronous, tightly regulated cellular proliferation and growth. Most importantly, this discovery has unlocked the potential to utilize pharmacologic blockade of activated downstream pathways to improve outcomes. This proposal aims to create a targeted laser algorithm for vascular stains with genotyping and deep, paired clinical phenotyping. In a small subset of patients with confirmed GNAQ/GNA11 genotyping, the investigators will utilize single cell spatial transcriptome profiling of affected tissue to drive drug discovery. Upon completion of this project, the investigators will have refined genotype-phenotype correlations enhanced by novel imaging of targeted tissue, all of which will accelerate precision-based treatments to prevent disfigurement and improve quality of life. These results will provide critical data for implementation of clinical trials that will shift treatment paradigms from a single, ineffective destructive treatment modality to a targeted pharmacologic intervention coupled with light. The investigators hypothesize that clearance of port wine birthmarks will require: 1) A precision-based approach including optimal laser dosimetry informed by novel angiographic imaging, genotype, and 2) pathway specific-targeted pharmacologic blockade of activated pathways informed by investigation of downstream effectors. The long-term goal is to shift treatment paradigms from a single ineffective destructive modality to a targeted laser source coupled with targeted topical therapy. Aim 1: Correlate genotype with clinical phenotype - 1.1 Correlate genotype with comprehensive phenotyping on available participants. When stratified by participant age, the hypothesis is that genotype will influence vessel size, with greater cell-cycle activation associated with larger median vessel diameter and depth on OCT. - 1.2 Correlate clinical phenotype with dynamic optical coherence tomography (OCT). The investigators hypothesize that participant age will be the greatest predictor of median vessel size and depth on OCT. - 1.3 Collect both quantitative and qualitative outcomes in participants treated with OCT to evaluate the participant experience utilizing this adjuvant modality in treatment. - 1.4 Integrate OCT data to create a targeted laser algorithm by age and/or genotype to optimize photo-coagulation of mutated cells. Aim 2: Determine the molecular mechanism of facial vascular stains to develop pathway-specific therapies - 2.1 In 4-6 children with confirmed GNAQ/GNA11 mutations, perform biopsies from affected and normal tissue, collect blood and saliva samples, to facilitate targeted high-depth next generation sequencing (NGS) - 2.2 Identify novel downstream genotype-specific targets using unbiased spatial transcriptomic analysis through single cell genotyping with targeted evaluation of 3 pathways for which topical inhibitors are currently in development (PiK3CA, mTOR, and MEK/ERK). Research Design: Once informed consent has been obtained, a visual skin exam will be done by the study dermatologist to document the cutaneous findings and photographs of the affected area(s) will be taken for this study. The photographs will be used to determine the genotype-phenotype correlations and will be shared with the coordinating center. Photographs will be stored electronically in a secure HIPAA compliant manner according to each site's policies. At the time of enrollment or at a subsequent visit, but only once during participation in the study, subjects can agree to provide any of the following non-medically necessary samples for genetic studies: blood sample, saliva sample, skin punch biopsy (normal skin or affected skin), surgical tissue specimens, paraffin-embedded tissue samples (from previous surgeries). Collection of any of these samples is optional. Clinical phenotyping of participants will be augmented through use of dynamic OCT to characterize the mean diameter and depth of blood vessels. OCT will be performed at baseline and prior to each standard of care laser treatment. Anatomic landmarks for choice of OCT placement will be decided by the study physician, with the goal to image the most prominent area of the stain. In a subset of subjects, OCT measurements will also be taken post standard of care laser treatment. A questionnaire will be completed at each visit by the participant and by the parent/guardian of participants ages 8-17 years. The questionnaire will ask how the participants and/or their parent/guardian feel about the results of the laser treatment and how they feel about using OCT in addition to their standard treatment.
Vascular Stains Optical Coherence Tomography (OCT) Vascular Staining
You can join if…
- Individual of any age from infant to adult
- Diagnosed with a vascular stain on any anatomic location based on the discretion of the study physician
- Has elected to receive standard of care laser treatment for their vascular stain
You CAN'T join if...
- University of California
not yet accepting patients
Irvine California 92697 United States
- University of Wisconsin
accepting new patients
Madison Wisconsin 53715 United States
- accepting new patients
- Start Date
- Completion Date
- University of Wisconsin, Madison
- Study Type
- Last Updated