Identifying the Genetic Predictors of Severe Acne Vulgaris and the Outcome of Oral Isotretinoin Treatment (SA)

The goal of this study is to enroll 250 participants that have joined the MURDOCK Study Horizon 1.5 (Duke IRB Pro00011196) with a current or prior diagnosis of severe acne AND current or prior treatment with oral isotretinoin. All 250 participants will answer a 5-page questionnaire designed to collect information on the diagnosis of severe acne and response to oral isotretinoin treatment. The aim is to identify genetic predictors of severe acne vulgaris and the outcome of oral isotretinoin treatment.

Study Overview

• Status: Completed
• Conditions: Acne Vulgaris; Isotretinoin

Detailed Description

Acne vulgaris is an under-studied common genetic disease with tremendous economic consequences. Acne vulgaris is one of the most common skin conditions treated by doctors. It affects 40-50 million people in the USA, with prevalence as high as 85% (recent study from Iran was 93%) in teenagers; 18% of woman have late onset (>25yr) acne vulgaris. Severe acne has a life-long psychosocial impact due to the significant scarring. Severe acne can also be associated with severe systemic inflammatory disease with fever, sterile osteomyelitis, inflammatory arthritis and other signs of systemic inflammatory responses. Some of these syndromes in Mendelian form (e.g. PAPA syndrome) have known genetic defects. Finally, while the data are inconclusive, there have been many suggestions that diet can exacerbate acne in some patients. The standard of care treatment for severe acne is systemic retinoid therapy, which, is usually, but not always effective. Unfortunately, systemic retinoid treatment is associated with significant toxicity, including common cutaneous adverse effects (dry lips, eyes, skin fragility), less common laboratory abnormalities such as elevated blood lipids, liver function abnormalities, and severe predictable teratogenicity. In addition, systemic therapy with retinoids has been associated with systemic diseases such as clinical depression, suicide, and inflammatory bowel disease, however the mechanisms and significance of these associations has not been determined. Given the frequency and severity of severe acne, the predictable severe toxicity of systemic retinoid therapy, and the already demonstrated genetic associations found in Mendelian forms of severe acne, it seems likely that significant genetic risk factors may be identified in patients with severe acne which would promote new and safer therapy, including dietary adjustment.

• Study Type: Observational
• Enrollment (Actual): 123

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Concord, North Carolina, United States, 28025
      • Carolinas Medical Center NorthEast Medical Arts Building
    • Concord, North Carolina, United States, 28025
      • Dermatology Group of the Carolinas
    • Davidson, North Carolina, United States, 28036
      • Ada Jenkins Center
    • Harrisburg, North Carolina, United States, 28075
      • Harrisburg Sleep Center
    • Huntersville, North Carolina, United States, 28078
      • Lake Norman Community Health Clinic
    • Kannapolis, North Carolina, United States, 28081
      • Kannapolis Internal Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 8 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Participants must enroll or have enrolled in the MURDOCK Study Community Registry and Biorepository prior to joining this Severe Acne Study. At the MURDOCK Study visit, or after the participant has enrolled in the MURDOCK Study, they will be asked (either in person or via phone) if they would be willing to join the Severe Acne Study.

Participants between ages 12 and 18 may also join the MURDOCK Study if they meet the eligibility criteria for this Severe Acne Study (a pediatric consent form will be used).

Description

Inclusion Criteria:

• Diagnosed with severe acne while age > 12 and < 18, and
• Completed at least one course of oral isotretinoin treatment; OR started treatment but discontinued prior to completion due to adverse side effects (with the exception of dry skin - see "exclusion criteria"); OR are currently undergoing and plan to complete treatment

Exclusion Criteria:

• Patients who are not willing to participate in this study
• Patients who experienced inflammatory bowel disease (IBD) prior to oral isotretinoin treatment
• Patients who did not complete the oral isotretinoin treatment because of pregnancy, dry skin, or reasons other than adverse side effects listed above
• Patients who are not willing to or cannot provide a blood sample for Murdock Study

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Retrospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Therapeutic response to isotretinoin	All 250 patients with severe acne will be genotyped using the Illumina 610 BeadChip. Whole-exome sequencing will be performed on 100 extremely severe acne vulgaris patients, selected based on severity and response to oral isotretinoin treatment. A case-control GWAS analysis will be performed (250 recruited patients vs. 1000 normal controls of convenience available in other studies at CHGV). Additionally, an association analyses will be conducted using complete exome sequencing data for the most severe cases, compared with controls of convenience (as an extreme trait in the population, there is a reasonable expectation of discovery of any important variants, rare or common). This analysis would also include targeted analysis on available drug response data (efficacy and adverse response).	10 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse reaccion to isotretinoin	All 250 patients with severe acne will be genotyped using the Illumina 610 BeadChip. Whole-exome sequencing will be performed on 100 extremely severe acne vulgaris patients, selected based on severity and response to oral isotretinoin treatment. A case-control GWAS analysis will be performed (250 recruited patients vs. 1000 normal controls of convenience available in other studies at CHGV). Additionally, an association analyses will be conducted using complete exome sequencing data for the most severe cases, compared with controls of convenience (as an extreme trait in the population, there is a reasonable expectation of discovery of any important variants, rare or common). This analysis would also include targeted analysis on available drug response data (efficacy and adverse response).	10 months

Collaborators and Investigators

• Sponsor: Duke University
• Investigators: Principal Investigator: Russell Hall, MD, Duke Medicine Site Based Research Group

Publications and helpful links

Helpful Links

• Murdock Study Severe Acne Study

Study record dates

Study Major Dates

• Study Start: September 1, 2011
• Primary Completion (Actual): August 1, 2015
• Study Completion (Actual): August 1, 2015

Study Registration Dates

• First Submitted: October 24, 2012
• First Submitted That Met QC Criteria: November 12, 2012
• First Posted (Estimate): November 16, 2012

Study Record Updates

• Last Update Posted (Actual): August 24, 2017
• Last Update Submitted That Met QC Criteria: August 23, 2017
• Last Verified: January 1, 2017

More Information

Terms related to this study

• Keywords: acne; isotretinoin; acne vulgaris; severe acne; severe acne vulgaris; Accutane; Sortret; Amnesteem; Claravis; Clarus; Decutan; Isotane; Izotek; Oratane; Isotret; Roaccutane
• Additional Relevant MeSH Terms: Skin Diseases; Acneiform Eruptions; Sebaceous Gland Diseases; Acne Vulgaris
• Other Study ID Numbers: Pro00030862