Weekly Isotretinoin Therapy Study

Study Overview
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Brief Summary
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In current Dermatology practice, options for moderate acne vulgaris remain limited. The mainstay of treatment for moderate acne remains long courses of oral antibiotics despite emerging antibiotic resistance. The efficacy of daily to twice daily dosed isotretinoin, an oral vitamin A derivative, for treatment of severe acne has been well established. The purpose of this study is to determine if once weekly dosed isotretinoin is effective for the treatment of patients with moderate acne. Additionally, the study aims to evaluate patient satisfaction and identify any adverse effects on this alternative dosing regimen.

Detailed Description
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In current Dermatology practice, options for moderate acne vulgaris remain limited. Moderate acne is clinically defined as acne that has not responded to at least three months of topical therapy and is not severe enough for initial treatment with a conventional course of isotretinoin (formerly known as Accutane). The mainstay of treatment for moderate acne remains long courses of oral antibiotics, mainly tetracyclines (doxycycline, minocycline) and occasionally trimethoprim-sulfamethoxazole. Males with moderate acne, in particular, are especially limited in their treatment options as they are not eligible for hormonal management (spironolactone, oral contraceptive pills) like their female counterparts. Additionally, even for those regardless of gender who may eventually qualify for a traditional isotretinoin course, many insurance companies first require failure to respond to at least three months of oral antibiotics. Nagler et. al found that the average antibiotic use for moderate to severe acne prior to receiving isotretinoin was 331 days, with 15.3% of patients prescribed antibiotics for three months or less, 88% for six months or more, and 46% for at least one year.1 Despite the widespread use of oral antibiotics in acne, antibiotic resistance is considered a global threat per the CDC2, and there have been calls to limit their use in acne because of concerns of bacterial resistance3,4,5. Because of this, there is a significant need for more research on alternative treatment options for moderate acne. Once weekly isotretinoin dosing has the potential to significantly improve moderate acne with good patient satisfaction and safety profile; however, no study findings on this treatment option have been published to date. The efficacy of isotretinoin, an oral vitamin A derivative, for treatment of acne has been well established. The traditional treatment course for severe acne consists of once to twice daily dosing (0.5-1 mg/kg/day) for 4-7 months (or 150mg/kg total cumulative dose). Though efficacious, there are numerous reported side-effects due to achieving the cumulative dose rapidly by once to twice daily dosing, such as severe dry skin, lips, and eyes, as well as liver enzyme and lipid abnormalities. Because of this, there have been studies exploring alternative isotretinoin dosing regimens including microdose, lower daily dose regimens (0.15-0.4 mg/kg/day6, 0.25-0.4 mg/kg/day7, 0.3-0.4 mg/kg/day8,9, in addition to 5 mg/day10 and 0.15-0.28 mg/kg/day with additional of local application of 1% clindamycin gel every other day11) and daily dosing for 7-10 consecutive days (0.5-0.7 mg/kg/day) out of each month only.7,12,13,14 All studies had favorable outcomes with alternative dosing, despite the lower total cumulative dose versus conventional dosing. Those who also analyzed adverse effect rates with alternative isotretinoin dosing found that these were either rarely observed or similar to conventional dosing.6,8,9,10,12,14 In contrast, the potential adverse effects of oral antibiotics used for acne include photosensitivity and nausea/vomiting (doxycycline), drug-induced pigment deposition and drug-induced systemic lupus erythematosus (minocycline), and angioedema and drug rashes including drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome (trimethoprim-sulfamethoxazole). Interestingly, rates of acne recurrence between alternative isotretinoin dosing and conventional dosing were similar at follow-up,6,7,9 despite a much older study from 1984 that found otherwise.15 Additionally, cost of alternative isotretinoin dosing was lower than with conventional dosing,8,9,13 and patient satisfaction was highest in the alternative dosing groups.7,10 For these reasons, this study aims to evaluate the efficacy of once weekly isotretinoin dosing (1-1.5 mg/kg/week) as a potential alternative to oral antibiotics for the treatment of patients with moderate acne. Secondary endpoints include patient satisfaction and adverse effects.

Official Title
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Weekly Isotretinoin Therapy for the Treatment of Moderate Acne Vulgaris

Conditions
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Acne Vulgaris

Intervention / Treatment
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* Drug: Isotretinoin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All patients 12 years and older with the diagnosis of moderate acne vulgaris Exclusion Criteria: Patients who are at baseline on long-term tetracycline antibiotics, long-term trimethoprim-sulfamethoxazole, or on spironolactone for any reason Patients who have taken isotretinoin in the past 6 months Patients with hypersensitivity to isotretinoin or to any of its components Females who are pregnant, likely to become pregnant, or will be breast-feeding during the study period Patients with a history of major depression, mania, or psychosis with an active episode during the past year including current psychotic symptoms and/or current suicidal ideation Adult patients with cognitive impairment Patients with baseline kidney or liver disease Patients with baseline hypertriglyceridemia Patients with history of or current pseudotumor cerebri Patients with any clinically significant unstable medical condition which could pose a risk to the safety of the patient Inability or unwillingness of subject or legal guardian/representative to give informed consent

Ages Eligible for Study
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Minimum Age: 12 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment Group<br> | Drug: Isotretinoin<br>* Participants will be getting isotretinoin (1-1.5 mg/kg/week)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants That Showed Improvement in Their Visible Acne (Efficacy of Once Weekly Isotretinoin) | Will look at clinical photos before, during, and after treatment and grade acne using a validated, clinical grading system (Comprehensive Acne Severity Scale, CASS) with 0 being clear skin and 5 being very severe acne. Participants are eligible for the study if their score is 3 or higher. An improvement in their visible acne is a score of 2, 1, or 0 at the end of the 4 months of treatment. | Baseline and end of treatment, approximately 4 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With a Change in Quality of Life | Participants will use the Dermatology Life Quality Index survey which measures how much their skin problems affect their life. 10 questions are asked with answers Very much,  A lot, A little, Not at all, or Not relevant. The answers correlate to a number (Very much =3,  A lot = 2, A little=1, Not at all= 0, Not relevant=0) and the answered are added together to get a score for that month. The higher the score the more their skin impacts their day to day activities. An improvement in their quality of life is a lower score at 4 months compared to baseline score. | Baseline, monthly, and end of treatment, total of 4 months | 
| Number of Side Effects Reported at the End of 4 Months | Participants will fill out a survey regarding nonserious and serious adverse events. | through study completion, an average of 4 months |