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

Acne Vulgaris Clinical Trial

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Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01727440
• Other study ID #: Pro00030862
• Status: Completed
• Phase: N/A
• First received: October 24, 2012
• Last updated: August 23, 2017
• Start date: September 2011
• Est. completion date: August 2015

Study information

• Verified date: January 2017
• Source: Duke University
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 123
• Est. completion date: August 2015
• Est. primary completion date: August 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Acne Vulgaris
• Isotretinoin

Locations

Country	Name	City	State
United States	Carolinas Medical Center Northeast Medical Arts Building	Concord	North Carolina
United States	Dermatology Group of the Carolinas	Concord	North Carolina
United States	Ada Jenkins Center	Davidson	North Carolina
United States	Harrisburg Sleep Center	Harrisburg	North Carolina
United States	Lake Norman Community Health Clinic	Huntersville	North Carolina
United States	Kannapolis Internal Medicine	Kannapolis	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Duke University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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

External Links

•   Murdock Study Severe Acne Study