Comparison Between Isotretinoin, Silymarin and Both in the Treatment of Acne Vulgaris

Comparative Study Between the Effect of Isotretinoin, Silymarin and Their Combination in the Treatment of Patients With Acne Vulgaris

This study aims to compare the effects of isotretinoin and silymarin or both in treatment of acne and their effects on the level of IGF-1, SAA1 and malondialdehyde (MDA) in acne patients.

Study Overview

• Status: Not yet recruiting
• Conditions: Acne Vulgaris
• Intervention / Treatment: Drug: Isotretinoin ,silymarin

Detailed Description

Acne vulgaris, a common and chronic disorder of the pilosebaceous unit, affects up to 85% of adolescent and young adults. The pathogenesis of acne is multifactorial. Traditionally, four distinct processes were believed to play critical roles: increased sebum production, alteration of keratinization processes leading to comedone formation, follicular colonization by Propionibacterium acnes (P.acnes) and inflammatory mediators around pilosebaceous unit.

Orally administered isotretinoin is currently the only agent that can affect all four main factors implicated in acne.

Serum insulin-like growth factor -1(IGF)-1 is a polypeptide hormone that has effects on sebocyte differentiation and proliferation. It leads to lipogenesis, and synthesis of inflammatory cytokines. IGF-1 also stimulates androgen synthesis leading to overproduction of sebum.

Propionibacterium acnes can increase the release of serum amyloid A1 (SAA1) .There is significant elevation of SAA1 in patients with acne, with a positive correlation with its severity.

Oxidative stress plays a role in the pathogenesis of acne in part due to the generation of reactive oxygen species (ROS) in response to infection by the bacterium Propionibacterium acnes, which colonizes the skin and grows in plugged hair follicles, thus attracting inflammatory cells, mainly neutrophils. These in turn secrete inflammatory mediators and generate ROS, which augments the inflammatory response and tissue damage.

Silymarin, the main active component of milk thistle consists of a mixture of flavonolignans and flavonoid taxifolin. Silymarin acts as a hepatoprotective, anticancer, anti-inflammatory and immunomodulatory agent.

Silymarin acts as a free radical scavenger, stabilizes the plasma membrane and reduces the production of inflammatory mediators produced by P. acnes, and scavenges the released free radicals.

• Study Type: Interventional
• Enrollment (Anticipated): 75
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Ghada M Tantawy, Doctor; Phone Number: 00201144062267; Email: Ghadamtantawy@gmail.com
• Study Contact Backup: Name: Sahar M El-hagger, Professor; Phone Number: 0020403336007

Study Locations

• Egypt
  • Tanta, Egypt
    • Tanta University
    • Contact: Dalia R Elafify, Doctor
    • Principal Investigator: Ghada M Tantawy, Doctor

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age: 16 years or more. Patient with moderate or severe acne. Not receiving acne treatment in the last month.

Exclusion Criteria:

• Pregnancy or lactation. Patients with known hypersensitivity to isotretinoin or silymarin. Patients with depression, liver diseases or high cholesterol. Patients with acromegaly. Patients with chronic inflammatory, infective or neoplastic disorders.

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

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: acne vulgaris patients group 1; acne patients will be rondomly assigned to 1 of the 3 interventions (isotretinoin, silymarin, or both)	Drug: Isotretinoin ,silymarin; 20mg/day isotretinoin for 3 months. 140 mg/day silymarin for 3 months. 20mg/day isotretinoin and 140mg/day silymarin for 3 months.
Experimental: acne vulgaris patients group 2; acne patients will be rondomly assigned to 1 of the 3 interventions (isotretinoin, silymarin, or both)	Drug: Isotretinoin ,silymarin; 20mg/day isotretinoin for 3 months. 140 mg/day silymarin for 3 months. 20mg/day isotretinoin and 140mg/day silymarin for 3 months.
Experimental: acne vulgaris patients group 3; acne patients will be rondomly assigned to 1 of the 3 interventions (isotretinoin, silymarin, or both)	Drug: Isotretinoin ,silymarin; 20mg/day isotretinoin for 3 months. 140 mg/day silymarin for 3 months. 20mg/day isotretinoin and 140mg/day silymarin for 3 months.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Global Acne Grading Classification	Global Acne Grading System (GAGS) Each is derived by multiplying the factors-2 for forehead, 2 for each check, 1 for nose, 1 for chin, 3 for both chest and back by the most heavily weighted lesion within each region (1 for ≥ one comedone, 2 for ≥ one papule,3 for ≥ one pustule, and 4 for ≥ one nodule).	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Liver function tests	Serum AST and ALT measure before and after 3 months therapy	3 months
Lipid profile	serum cholesterol, TG, LDL and HDL levels in blood before and after 3 months therapy	3 months
Insulin growth factor -1	Assessment of IGF-1 level in blood before and after 3 months therapy	3 months
serum amyloid A1	Assessment of serum amyloid A1 level before and after 3 months therapy	3 months
Malondialdehyde	Assessment of Malondialdehyde level in blood before and after 3 months therapy	3 months

Collaborators and Investigators

• Sponsor: Tanta University
• Investigators: Study Chair: Ghada F Hassan, A.professor, Tanta University; Study Chair: Dalia R Elafify, Doctor, Tanta University

Publications and helpful links

General Publications

• Hazarika N. Acne vulgaris: new evidence in pathogenesis and future modalities of treatment. J Dermatolog Treat. 2021 May;32(3):277-285. doi: 10.1080/09546634.2019.1654075. Epub 2019 Aug 29.
• Shie Morteza M, Hayati Z, Namazi N, Abdollahimajd F. Efficacy and safety of oral silymarin in comparison with oral doxycycline and their combination therapy in the treatment of acne vulgaris. Dermatol Ther. 2019 Nov;32(6):e13095. doi: 10.1111/dth.13095. Epub 2019 Oct 21.

Study record dates

Study Major Dates

• Study Start (Anticipated): January 1, 2023
• Primary Completion (Anticipated): November 1, 2023
• Study Completion (Anticipated): January 1, 2024

Study Registration Dates

• First Submitted: December 8, 2022
• First Submitted That Met QC Criteria: December 18, 2022
• First Posted (Actual): December 28, 2022

Study Record Updates

• Last Update Posted (Actual): December 28, 2022
• Last Update Submitted That Met QC Criteria: December 18, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Acneiform Eruptions; Sebaceous Gland Diseases; Acne Vulgaris; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Protective Agents; Dermatologic Agents; Antioxidants; Isotretinoin; Silymarin
• Other Study ID Numbers: Treatment of acne vulgaris

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
• product manufactured in and exported from the U.S.: No