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History of Changes for Study: NCT04772911
Multicenter Phenotype-Genotype Analysis of Vascular Stains to Optimize Treatment Utilizing Optical Coherence Tomography
Latest version (submitted September 6, 2022) on ClinicalTrials.gov
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Study Record Versions
Version A B Submitted Date Changes
1 February 24, 2021 None (earliest Version on record)
2 March 9, 2021 Recruitment Status, Study Status and Contacts/Locations
3 April 20, 2021 Study Status
4 September 16, 2021 Groups and Interventions, Study Description, Study Status, Eligibility, Study Design and Study Identification
5 December 21, 2021 Study Status and Contacts/Locations
6 April 15, 2022 Study Status
7 September 6, 2022 Study Description, Study Status, Outcome Measures, Groups and Interventions, Study Design and Study Identification
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Study NCT04772911
Submitted Date:  February 24, 2021 (v1)

Open or close this module Study Identification
Unique Protocol ID: 2020-1351
Brief Title: Multicenter Phenotype-Genotype Analysis of Vascular Stains to Optimize Treatment Utilizing Optical Coherence Tomography
Official Title: Multicenter Phenotype-Genotype Analysis of Vascular Stains to Optimize Treatment Utilizing Optical Coherence Tomography
Secondary IDs: A534300 [UW Madison]
SMPH/DERMATOLOGY [UW Madison]
Protocol Version 2/19/2021 [UW Madison]
Open or close this module Study Status
Record Verification: February 2021
Overall Status: Not yet recruiting
Study Start: April 2021
Primary Completion: April 2022 [Anticipated]
Study Completion: April 2022 [Anticipated]
First Submitted: February 24, 2021
First Submitted that
Met QC Criteria:
February 24, 2021
First Posted: February 26, 2021 [Actual]
Last Update Submitted that
Met QC Criteria:
February 24, 2021
Last Update Posted: February 26, 2021 [Actual]
Open or close this module Sponsor/Collaborators
Sponsor: University of Wisconsin, Madison
Responsible Party: Sponsor
Collaborators:
Open or close this module Oversight
U.S. FDA-regulated Drug: No
U.S. FDA-regulated Device: No
Data Monitoring: No
Open or close this module Study Description
Brief Summary: 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.
Detailed Description:

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.

Open or close this module Conditions
Conditions: Vascular Stains
Keywords:
Open or close this module Study Design
Study Type: Observational
Observational Study Model: Case-Control
Time Perspective: Prospective
Biospecimen Retention: Samples With DNA
Biospecimen Description:

Each collection will occur 1 time while the subject is on study if they consent to the sample collection.

  • Blood - approximately 4mL will be collected (approximately 5 min)
  • Saliva Sample - 1-2 tubes of saliva will be collected (approximately 2 min)
  • Skin Punch Biopsy (affected and normal skin area) - one or two 3-4mm punch biopsy will be taken (approximately 20 min)
  • Fresh surgical tissue - a small amount of fresh tissue, at least 3-4mm in diameter (no time commitment from the subject)
  • Slides/blocks - up to 10 unstained slides or a block of archived tissue will be requested. (no time commitment from the participant)
Enrollment: 85 [Anticipated]
Number of Groups/Cohorts 1
Open or close this module Groups and Interventions
Groups/Cohorts Interventions
Vascular Staining
Patients diagnosed with vascular stains.
Device: Optical Coherence Tomography (OCT)
OCT will be performed at baseline and prior to each standard of care laser treatment to characterize the mean diameter and depth of blood vessels.
Open or close this module Outcome Measures
Primary Outcome Measures:
1. Correlation between blood vessel size measured via OCT and genotype of affected tissues
[ Time Frame: up to 1 month ]

Targeted next generation sequencing (NGS) using a hybrid capture approach will be performed on DNA samples from affected tissues. OCT measurements of blood vessel size will be compared to genotype derived from biospecimen.
Other Outcome Measures:
1. Correlation of genotype with phenotype
[ Time Frame: up to 1 month ]

Regression analysis will be used to estimate the effect of genotype on clinical phenotype adjusting for age, sex, race, ethnicity, and other potential confounders.
Open or close this module Eligibility
Study Population: Diagnosed with a vascular stain on any anatomic location based on the discretion of the study physician
Sampling Method: Non-Probability Sample
Minimum Age:
Maximum Age:
Sex: All
Gender Based:
Accepts Healthy Volunteers: No
Criteria:

Inclusion Criteria:

  • 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

Exclusion Criteria:

-

Open or close this module Contacts/Locations
Central Contact Person: Heather Neils
Telephone: (608) 287-2640
Email: hneils@dermatology.wisc.edu
Study Officials: Lisa Arkin, MD
Principal Investigator
University of Wisconsin, Madison
Locations: United States, California
University of California
Irvine, California, United States, 92697
Contact:Sub-Investigator: Kristen Kelly, MD
United States, Wisconsin
University of Wisconsin
Madison, Wisconsin, United States, 53715
Contact:Contact: Heather Neils 608-287-2640 hneils@dermatology.wisc.edu
Contact:Principal Investigator: Lisa Arkin, MD
Contact:Sub-Investigator: Beth Drolet, MD
Open or close this module IPDSharing
Plan to Share IPD: No
Open or close this module References
Citations:
Links:
Available IPD/Information:

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