Oral Isotretinoin in Melasma a Randomized Controlled Trial

Oral Isotretinoin in The Treatment of Melasma A Randomized Controlled Clinical Trial

Melasma is a common refractory acquired hyperpigmentation of the skin having a serious impact on patients' quality of life. Melasma is challenging to treat. Treatment is often a multimodality approach. Due to the attached psychological and social stress, it is important to counsel patients with melasma adequately about the chronicity of the disease, the importance of photoprotection, and the role of hormones in disease persistence before embarking on therapeutic correction. So in this study, we are exploring the efficacy of oral isotretinoin for treating melasma.

Study Overview

• Status: Recruiting
• Conditions: Melasma
• Intervention / Treatment: Drug: Isotretinoin; Drug: Triple combination formula

Detailed Description

Melasma has a significant impact on the quality of life and self-esteem of those affected. Darker skin photo types e.g. Egyptians have excess potential to develop melasma.

Melasma is a chronic and challenging condition to manage. Previous treatment modalities have been unsatisfactory.

Oral isotretinoin is a potential treatment modality for melasma that has not been investigated yet.

In this study we aim to evaluate the efficacy and the tolerability of oral isotretinoin in the treatment of melasma and to compare its efficacy and tolerability with the current gold standard "topical triple combination formula"

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Hagar Nofal, Dr.; Phone Number: +201006387707; Email: hagarnofal@aucegypt.edu

Study Locations

• Egypt
  • Select Region
    • Zagazig, Select Region, Egypt, 44511
      • Recruiting
      • Dermatology department, Zagazig University Hospitals, Faculty of Medicine, Zagazig University
      • Contact: Hagar Nofal, Dr.; Phone Number: 01006387707; Email: hagarnofal@aucegypt.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age between 18 and 50 years
2. Patients complaining of melasma.
3. Patients with all types of melasma (epidermal, dermal and mixed)
4. Sexually active women who is willing to follow at least 2 types of contraceptive methods during study period
5. Patients with skin type I-V

Exclusion Criteria:

1. Pregnant or nursing women.
2. Women on any concurrent therapy for melasma.
3. Patients that are using any therapy for melasma for the last 45 days.
4. Patient with abnormal liver function test or lipid profile.
5. Patients with allergy or hypersensitivity to the assigned drugs.
6. Women not willing to follow contraceptive methods at time of study.
7. Patients on facial treatments or photosensitizing drugs within previous 6 months.
8. Patients with back or joint pain.
9. Patients with pre-existing or dormant dermatologic disease on the face that could interfere with the outcome of the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Isotretinoin; patients will receive oral isotretinoin (1 mg/kg/day) for 3 months	Drug: Isotretinoin; Patients will receive 1mg/kg/day for 3 months
Active Comparator: Kligman Formula arm; patients will receive topical triple combination formula at night everyday over the affected areas for 3 months	Drug: Triple combination formula; Patients are instructed to apply the triple combination formula at night daily for 3 months; Other Names: modified Kligman formula

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response to treatment	Treatment efficacy will be assessed by the change in disease severity measured in mMASI at the end of the treatment period, and the difference in the global appearance of melasma through standardized photographs using Global Aesthetic Improvement Scale (GAIS) using a five-point ordinal scale (1 = exceptionally improved appearance, 2 = very improved appearance, 3 = improved appearance, 4 = unaltered appearance, 5 = worsened appearance). The duration taken till complete clearance will be assessed as well.	three months
Time to complete clearance	The duration taken till complete clearance will be assessed as well.	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quality of life index	The change in patients' quality of life using the difference between results of "Melasma Quality of Life Index" at baseline and end of treatment.	12 weeks
Treatment tolerability	Treatment tolerability will be assessed in terms of the side effects reported by the investigator or the patients in follow-up visits including but not limited to; facial erythema, scaling, a burning sensation, and cheilitis. Patients' compliance assessed by the percentage of patients withdraw from each arm of the study and the number of days per week the patients' take/apply their medication.	12 weeks

Collaborators and Investigators

• Sponsor: Zagazig University

Publications and helpful links

General Publications

• Artzi O, Horovitz T, Bar-Ilan E, Shehadeh W, Koren A, Zusmanovitch L, Mehrabi JN, Salameh F, Isman Nelkenbaum G, Zur E, Sprecher E, Mashiah J. The pathogenesis of melasma and implications for treatment. J Cosmet Dermatol. 2021 Nov;20(11):3432-3445. doi: 10.1111/jocd.14382. Epub 2021 Aug 19.
• Garner ML, McShane DB, Burkhart CN, Morrell DS. Isotretinoin and vitiligo: can chronic cheilitis cause koebnerization? Pediatr Dermatol. 2015 May-Jun;32(3):e108-9. doi: 10.1111/pde.12538. Epub 2015 Mar 17.
• Muthu SK, Narang T, Saikia UN, Kanwar AJ, Parsad D, Dogra S. Low-dose oral isotretinoin therapy in lichen planus pigmentosus: an open-label non-randomized prospective pilot study. Int J Dermatol. 2016 Sep;55(9):1048-54. doi: 10.1111/ijd.13293. Epub 2016 Apr 7.

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2023
• Primary Completion (Estimated): January 31, 2024
• Study Completion (Estimated): May 31, 2024

Study Registration Dates

• First Submitted: December 30, 2023
• First Submitted That Met QC Criteria: December 30, 2023
• First Posted (Actual): January 11, 2024

Study Record Updates

• Last Update Posted (Actual): January 11, 2024
• Last Update Submitted That Met QC Criteria: December 30, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Hyperpigmentation; Pigmentation Disorders; Melanosis; Dermatologic Agents; Isotretinoin
• Other Study ID Numbers: ZU-IRB#10462/26-2-2023

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The study protocol and a copy of the master sheet for data collection, the statistical analysis plan will be shared and the results will be published in a respective journal
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No