Comedone Extraction and Oral Doxycycline In The First Line Treatment of Moderate Acne Vulgaris

Effectiveness of Comedone Extraction and Oral Doxycycline In The First Line Treatment of Moderate Acne Vulgaris: Study on HIF-1 Alpha Expression

The objective of the study was to evaluate the effectiveness of comedone extraction compared to oral antibiotics as the main therapy of moderate acne vulgaris (MAV); and to determine the expression of HIF-1 alpha by examining the immunohistochemistry and ELISA as a sign of hypoxia/anoxia in MAV lesion. This was a randomized, placebo-controlled clinical trial that was performed in 2015 at three different dermatology clinics in Indonesia, Cipto Mangunkusumo Hospital Jakarta, Gatot Soebroto Army Hospital Jakarta, and PT. Mattel Indonesia, Cikarang. One hundred and twenty eight subjects with moderate acne vulgaris were recruited and randomized to receive either oral doxycycline or comedone extraction for six weeks. Subjects who had acne lesion and the back area were offered skin lesion biopsy to evaluate immunohistochemistry and ELISA before administration of medication. The main outcome was total reduction of inflammatory and non inflammatory lesions, evaluated every two weeks.

Study Overview

• Status: Completed
• Conditions: Acne Vulgaris
• Intervention / Treatment: Drug: Doxycycline Capsule; Procedure: Comedone extraction

Detailed Description

Acne vulgaris (AV) is a polymorphic disease, characterized by inflammatory and noninflammatory lesions. Systemic antibiotics play a role as the first line therapy of moderate acne vulgaris treatment. Since bacterial resistance tends to increase, alternative therapy for moderate acne vulgaris is needed.

This study aims to evaluate the effectiveness of comedone extraction compared to oral antibiotics as the main therapy of moderate acne vulgaris; and to etermine the expression of HIF-1 alpha by examining the immunohistochemistry and ELISA as a sign of hypoxia/anoxia in MAV lesion.

This was a randomized, placebo-controlled clinical trial that was performed in 2015 at three different dermatology clinics in Indonesia, Cipto Mangunkusumo Hospital Jakarta, Gatot Soebroto Army Hospital Jakarta, and PT. Mattel Indonesia, Cikarang.

One hundred and twenty eight subjects, aged between 15 and 50 years, with moderate acne vulgaris were recruited and randomized to receive either oral doxycycline (100 mg) or comedone extraction for six weeks. Subjects who had acne lesion and the back area were offered skin lesion biopsy to evaluate immunohistochemistry and ELISA before administration of medication.

At each follow-up visit, subjects were asked to grade the overall response and questioned regarding adverse events. The objective or main outcome was total reduction of inflammatory and noninflammatory lesions.

• Study Type: Interventional
• Enrollment (Actual): 140
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 13 years to 48 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients with moderate acne vulgaris based on clinical manifestation of face (20-100 comedones, 15-50 inflammatory lesions, and/or 30-125 total lesions)
• Age range of 15 to 50 years old

Exclusion Criteria:

• History of oral antibiotics consumption within 2 weeks preceding this study
• Usage of topical retinoid in less than previous 2 weeks
• History of systemic retinoid consumption within 3 months preceding this study
• Pregnant of breastfeeding women
• Consuming oral contraception during examination
• Drug allergy or skin manifestation due to side effect of moderate acne vulgaris first line therapy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Doxycycline Group; Subjects were randomized to receive Doxycycline capsules. The capsules were taken once daily for 6 weeks and evaluated every 2 weeks.	Drug: Doxycycline Capsule; Doxycycline capsule 100 mg/day, tretinoin cream 0.05% on face every night, benzoyl peroxide gel 2.5% on face in the morning and afternoon.
Active Comparator: Comedone Extraction Group; Subjects were randomized to receive comedone extraction. Comedone extraction were done three times, and evaluated every 2 weeks.	Procedure: Comedone extraction; Comedone extraction, tretinoin cream 0.05% on face every night, benzoyl peroxide gel 2.5% on face in the morning and afternoon.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from Baseline Inflammatory Lesions at 2 weeks	Numeric data of total reduction (improvement) of inflammatory lesions (Baseline inflammatory lesion count) - (Week 2 inflammatory lesion count) __________________________________________________________ x 100% Baseline inflammatory lesion count	2 weeks
Change from Baseline Inflammatory Lesions at 4 weeks	Numeric data of total reduction (improvement) of inflammatory lesions (Baseline inflammatory lesion count) - (Week 4 inflammatory lesion count) __________________________________________________________ x 100% Baseline inflammatory lesion count	4 weeks
Change from Baseline Inflammatory Lesions at 6 weeks	Numeric data of total reduction (improvement) of inflammatory lesions (Baseline inflammatory lesion count) - (Week 6 inflammatory lesion count) __________________________________________________________ x 100% Baseline inflammatory lesion count	6 weeks
Change from Baseline Non-Inflammatory Lesions at 2 weeks	Numeric data of total reduction (improvement) of non-inflammatory lesions (Baseline non-inflammatory lesion count) - (Week 2 non-inflammatory lesion count) __________________________________________________________ x 100% Baseline non-inflammatory lesion count	2 weeks
Change from Baseline Non-Inflammatory Lesions at 4 weeks	Numeric data of total reduction (improvement) of non-inflammatory lesions (Baseline non-inflammatory lesion count) - (Week 4 non-inflammatory lesion count) __________________________________________________________ x 100% Baseline non-inflammatory lesion count	4 weeks
Change from Baseline Non-Inflammatory Lesions at 6 weeks	Numeric data of total reduction (improvement) of non-inflammatory lesions (Baseline non-inflammatory lesion count) - (Week 6 non-inflammatory lesion count) __________________________________________________________ x 100% Baseline non-inflammatory lesion count	6 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Subjective Improvement at 2 weeks	Improvement of clinical manifestation based on subjective complaints. Subjects were asked to grade overall response using rating scale (0-4), with higher score means a better outcome (0) no or minimal improvement; mild improvement; moderate improvement; robust improvement; very good improvement	2 weeks
Subjective Improvement at 4 weeks	Improvement of clinical manifestation based on subjective complaints. Subjects were asked to grade overall response using rating scale (0-4), with higher score means a better outcome (0) no or minimal improvement; mild improvement; moderate improvement; robust improvement; very good improvement	4 weeks
Subjective Improvement at 6 weeks	Improvement of clinical manifestation based on subjective complaints. Subjects were asked to grade overall response using rating scale (0-4), with higher score means a better outcome (0) no or minimal improvement; mild improvement; moderate improvement; robust improvement; very good improvement	6 weeks
Number of Participants with Side Effects at 2 weeks	Mild side effects if it did not need further management and research medication could be continued.; Moderate side effects if clinical manifestations were robust, itchy, pain, erythematous, yet did not need further management and temporary.; Severe side effects if it interfered daily activity, such as burn and pain sensastion, erythematous skin, edema, skin exfoliation, that needed further management.	2 weeks
Number of Participants with Side Effects at 4 weeks	Mild side effects if it did not need further management and research medication could be continued.; Moderate side effects if clinical manifestations were robust, itchy, pain, erythematous, yet did not need further management and temporary.; Severe side effects if it interfered daily activity, such as burn and pain sensastion, erythematous skin, edema, skin exfoliation, that needed further management.	4 weeks
Number of Participants with Side Effects at 6 weeks	Mild side effects if it did not need further management and research medication could be continued.; Moderate side effects if clinical manifestations were robust, itchy, pain, erythematous, yet did not need further management and temporary.; Severe side effects if it interfered daily activity, such as burn and pain sensastion, erythematous skin, edema, skin exfoliation, that needed further management.	6 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Expression of Antibody HIF-1 Alpha with Immunohistochemistry Examination	Analysis of HIF-1 Alpha expression on keratinocyte cell of pilosebaceous ducts (samples from skin lesion biopsy) was examined with immunohistochemistry using antibody HIF-1 alpha which was visualized with microscope and photographed to achieve qualitative data.	Baseline
Expression of Antibody HIF-1 Alpha with ELISA Examination	The measurement of HIF-1 Alpha protein concentration in the sebaceous follicle ducts was conducted through ELISA examination with Cusabio Human Hypoxia-inducible factor	Baseline

Collaborators and Investigators

• Sponsor: Indonesia University
• Investigators: Principal Investigator: Irma B Sitohang, MD, PhD, Fakultas Kedokteran Universitas Indonesia

Publications and helpful links

General Publications

• Sitohang IBS, Soebaryo RW, Kanoko M. Acne Lesion Extraction versus Oral Doxycycline for Moderate Acne Vulgaris: A Randomized Clinical Trial. J Clin Aesthet Dermatol. 2021 Jun;14(6):E61-E65. Epub 2021 Jun 1.

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2015
• Primary Completion (Actual): September 30, 2015
• Study Completion (Actual): October 14, 2015

Study Registration Dates

• First Submitted: December 17, 2019
• First Submitted That Met QC Criteria: December 19, 2019
• First Posted (Actual): December 20, 2019

Study Record Updates

• Last Update Posted (Actual): December 20, 2019
• Last Update Submitted That Met QC Criteria: December 19, 2019
• Last Verified: December 1, 2019

More Information

Terms related to this study

• Keywords: moderate acne vulgaris; comedone extraction; oral doxycycline; HIF-1 alpha expression
• Additional Relevant MeSH Terms: Skin Diseases; Acneiform Eruptions; Sebaceous Gland Diseases; Acne Vulgaris; Anti-Infective Agents; Anti-Bacterial Agents; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Doxycycline
• Other Study ID Numbers: ComExt

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No