Acne Vulgaris
Conditions
Brief summary
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
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.
Interventions
DRUGIsotretinoin
Participants will be getting isotretinoin (1-1.5 mg/kg/week)
Sponsors
Medical University of South Carolina
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Masking description
The study member assessing change in acne using the Comprehensive Acne Severity Scale does not know the medication the participants are taking.
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants That Showed Improvement in Their Visible Acne (Efficacy of Once Weekly Isotretinoin) | Baseline and end of treatment, approximately 4 months | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With a Change in Quality of Life | Baseline, monthly, and end of treatment, total of 4 months | 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. |
| Number of Side Effects Reported at the End of 4 Months | through study completion, an average of 4 months | Participants will fill out a survey regarding nonserious and serious adverse events. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Treatment Group Isotretinoin: Participants will be getting isotretinoin (1-1.5 mg/kg/week) | 22 |
| Total | 22 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Lost to Follow-up | 3 |
Baseline characteristics
| Characteristic | Treatment Group | — |
|---|---|---|
| Age, Continuous | 24.77 years STANDARD_DEVIATION 8.74 | — |
| Race and Ethnicity Not Collected | — | — Participants |
| Region of Enrollment United States | 22 Participants | — |
| Sex: Female, Male Female | 13 Participants | — |
| Sex: Female, Male Male | 9 Participants | — |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 19 |
| other Total, other adverse events | 12 / 19 |
| serious Total, serious adverse events | 0 / 19 |
Outcome results
Primary
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.
Time frame: Baseline and end of treatment, approximately 4 months
Population: The amount of participants that were analyzed is less than the original number enrolled. There were 3 participants that did not complete the study and were not analyzed at the end of the 4 months of treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment Group | Number of Participants That Showed Improvement in Their Visible Acne (Efficacy of Once Weekly Isotretinoin) | 18 Participants |
Secondary
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.
Time frame: Baseline, monthly, and end of treatment, total of 4 months
Population: Three subjects did not complete the study for analysis.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment Group | Number of Participants With a Change in Quality of Life | 17 Participants |
Secondary
Number of Side Effects Reported at the End of 4 Months
Participants will fill out a survey regarding nonserious and serious adverse events.
Time frame: through study completion, an average of 4 months
Population: 3 participants were lost to follow up and did not complete the final adverse event questionnaire. One participant can have more than one event.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment Group | Number of Side Effects Reported at the End of 4 Months | 24 events |