Clincosm LogoSign in Get a demo

WIT: Weekly Isotretinoin Therapy Study

Sponsor
Medical University of South Carolina (Other)
Overall Status
Completed
CT.gov ID
NCT04594759
Collaborator
(none)
22
Enrollment
1
Location
1
Arm
13.3
Actual Duration (Months)
1.7
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 1/Phase 2

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.

Study Design

Study Type:
Interventional
Actual Enrollment :
22 participants
Allocation:
Non-Randomized
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Masking Description:
The study member assessing change in acne using the Comprehensive Acne Severity Scale does not know the medication the participants are taking.
Primary Purpose:
Treatment
Official Title:
Weekly Isotretinoin Therapy for the Treatment of Moderate Acne Vulgaris
Actual Study Start Date :
Nov 11, 2020
Actual Primary Completion Date :
Dec 21, 2021
Actual Study Completion Date :
Dec 21, 2021

Arms and Interventions

Arm Intervention/Treatment
Experimental: Treatment Group

Drug: Isotretinoin
Participants will be getting isotretinoin (1-1.5 mg/kg/week)

Outcome Measures

Primary Outcome Measures

  1. 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 Outcome Measures

  1. 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.

  2. 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.

Eligibility Criteria

Criteria

Ages Eligible for Study:
12 Years and Older
Sexes Eligible for Study:
All
Accepts 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

Contacts and Locations

Locations

Site City State Country Postal Code
1 Samantha Karline Charleston South Carolina United States 29403

Sponsors and Collaborators

  • Medical University of South Carolina

Investigators

  • Principal Investigator: Samantha Karlin, MD, Medical University of South Carolina

Study Documents (Full-Text)

More Information

Publications

Responsible Party:
Samantha Karlin, MD, Dermatology Resident Principal Investigator, Medical University of South Carolina
ClinicalTrials.gov Identifier:
NCT04594759
Other Study ID Numbers:
  • 00103493
First Posted:
Oct 20, 2020
Last Update Posted:
May 9, 2022
Last Verified:
Apr 1, 2022
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Product Manufactured in and Exported from the U.S.:
No
Additional relevant MeSH terms:
Acne Vulgaris
Isotretinoin

Study Results

Participant Flow

Recruitment Details
Pre-assignment Detail
Arm/Group Title Treatment Group
Arm/Group Description Isotretinoin: Participants will be getting isotretinoin (1-1.5 mg/kg/week)
Period Title: Overall Study
STARTED 22
COMPLETED 19
NOT COMPLETED 3

Baseline Characteristics

Arm/Group Title Treatment Group
Arm/Group Description Isotretinoin: Participants will be getting isotretinoin (1-1.5 mg/kg/week)
Overall Participants 22
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]
24.77
(8.74)
Sex: Female, Male (Count of Participants)
Female
13
59.1%
Male
9
40.9%
Race and Ethnicity Not Collected (Count of Participants)
Region of Enrollment (Count of Participants)
United States
22
100%

Outcome Measures

1. Primary Outcome
Title Number of Participants That Showed Improvement in Their Visible Acne (Efficacy of Once Weekly Isotretinoin)
Description 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

Outcome Measure Data

Analysis Population Description
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/Group Title Treatment Group
Arm/Group Description Isotretinoin: Participants will be getting isotretinoin (1-1.5 mg/kg/week)
Measure Participants 19
Count of Participants [Participants]
18
81.8%
2. Secondary Outcome
Title Number of Participants With a Change in Quality of Life
Description 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

Outcome Measure Data

Analysis Population Description
Three subjects did not complete the study for analysis.
Arm/Group Title Treatment Group
Arm/Group Description Isotretinoin: Participants will be getting isotretinoin (1-1.5 mg/kg/week)
Measure Participants 19
Count of Participants [Participants]
17
77.3%
3. Secondary Outcome
Title Number of Side Effects Reported at the End of 4 Months
Description Participants will fill out a survey regarding nonserious and serious adverse events.
Time Frame through study completion, an average of 4 months

Outcome Measure Data

Analysis Population Description
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/Group Title Treatment Group
Arm/Group Description Isotretinoin: Participants will be getting isotretinoin (1-1.5 mg/kg/week)
Measure Participants 19
Number [events]
24

Adverse Events

Time Frame Through study completion, an average of 4 months. Participants could have more than one adverse event.
Adverse Event Reporting Description
Arm/Group Title Treatment Group
Arm/Group Description Isotretinoin: Participants will be getting isotretinoin (1-1.5 mg/kg/week)
All Cause Mortality
Treatment Group
Affected / at Risk (%) # Events
Total 0/19 (0%)
Serious Adverse Events
Treatment Group
Affected / at Risk (%) # Events
Total 0/19 (0%)
Other (Not Including Serious) Adverse Events
Treatment Group
Affected / at Risk (%) # Events
Total 12/19 (63.2%)
Musculoskeletal and connective tissue disorders
Mild myalgias 11/19 (57.9%)
Skin and subcutaneous tissue disorders
Dry lips/eyes 10/19 (52.6%)
Dry skin 11/19 (57.9%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

Name/Title Dr. Samantha Karlin
Organization Medical University of South Carolina
Phone (843)- 714-0146
Email karlin@musc.edu
Responsible Party:
Samantha Karlin, MD, Dermatology Resident Principal Investigator, Medical University of South Carolina
ClinicalTrials.gov Identifier:
NCT04594759
Other Study ID Numbers:
  • 00103493
First Posted:
Oct 20, 2020
Last Update Posted:
May 9, 2022
Last Verified:
Apr 1, 2022