Clinical trial NCT05622916: Topical Ethanol Extract (Piper Crocatum) for Anogenital Warts
Official title: The Efficacy of Ethanol Extract of Red Betel Leaves (Piper Crocatum) as Topical Patient-Applied Therapy In Anogenital Warts The Study of Foxp3+ Treg, Tumor Growth Factor (TGF)-β1, and Interferon (IFN)-γ Expression
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Anogenital Wart
Keywords: Anogenital Wart
Trichloroacetic
Piper crocatum
Clinical Efficacy
Inflammatory Marker
Lead sponsor: Hasanuddin University
Sponsor class: OTHER
First posted: 2022-11-21
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: One group will receive the intervention, whereas the comparison group will receive standard care
Primary purpose: TREATMENT

Brief summary: This clinical trial aims to assess the efficacy of topical Piper crocatum in treating Anogenital warts. It aims to answer

* the clinical efficacy of treating anogenital warts
* the expression of Foxp3+ regulatory T (Treg), TGF/Tumor Growth Factor -β1, and IFN/interferon -γ of anogenital wart lesion Participants will be allocated into two topical treatments, intervention and active comparator Trichloroacetic Acid (TCA) 90%. The researchers assume that intervention is superior compared to TCA 90%

Detailed description: Study Design :

A randomized controlled trial

Population:

Diagnosed with Condyloma Acuminata (International Classification of Disease 10 code A.63.0)

Intervention period :

8 weeks of daily topical intervention with follow-up at week 12

Detailed formulation

1. Extraction of Piper crocatum with ethanol assisted in a microwave-assisted extraction (MAE)
2. The dissolution and active substances are separated by evaporation using a rotary evaporator to obtain the extract in the form of a thick solution
3. freeze-drying is performed to obtain a stable thick extract
4. preparation of ointment by adding formulation of ethanol extract of red betel leaves with 50 mg of white vaseline to achieve 30% concentration

Settings:

Outpatient care at the designated hospital

Participants:

Consecutive recruitment

Sample Size Estimation:

Following the formula of two different means, with the indicator, as follows:

1. Type 1 error 5%
2. Power of Study 80%
3. Assuming the effect size of cohen d (in reducing the size of warts) is 0.5
4. equal allocation between two arms total sample: 100 participants

Proposed analysis:

Intention to treat (ITT) with sensitivity and subgroup analysis

Eligibility criteria: Inclusion Criteria:

1. Men and women diagnosed with external anogenital warts
2. Clinical lesions of Anogenital Wart at least 3 lesions with a size of 1-5 cm
3. In patients with HIV, Cluster of Differentiation 4 (CD4)cell count \>350 cells/mm and have been taking antiretroviral (ARV) drugs regularly for 3 months,

Exclusion Criteria:

1. Pregnant or lactating women
2. Lesions located in the external urethral orifice and vagina
3. Using systemic immunomodulators/immunosuppressants

The protocol treatment will be discontinued if patients

a. Withdraw their consent based on the patient's demand d. Severe adverse events occurred or allergies to the components of the test product b. After undergoing clinical trials, the patient experienced things that caused him/her to no longer meet the criteria set out in this protocol. c. Subjects do not comply the established study protocol

Primary outcomes:
measure: Size of wart
timeFrame: Changes of wart size from baseline to week 12
measure: Foxp3+ regulatory T (Treg)
timeFrame: change of Foxp3+ regulatory T (Treg) expression from baseline to week 8
measure: TGF-β1
timeFrame: change of TGF-β1 expression from baseline to week 8
measure: IFN-γ
timeFrame: change of IFN-γ expression from baseline to week 8
Secondary outcomes:
Other outcomes:
measure: Adverse reaction
timeFrame: any adverse event from baseline to week 12
Locations:
city: Makassar
country: Indonesia
facility: Wahidin Sudirohusodo General Hospital
state: South Sulawesi
Study officials:
affiliation: Hasanuddin University
name: Idrianti Idrus, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Indonesia University
name: Wresti Indriatmi, MD. Ph.D
role: PRINCIPAL_INVESTIGATOR
affiliation: Indonesia University
name: Fransiscus Suyatna, MD. Ph.D
role: PRINCIPAL_INVESTIGATOR
References:
citation: Sherrard J, Riddell L. Comparison of the effectiveness of commonly used clinic-based treatments for external genital warts. Int J STD AIDS. 2007 Jun;18(6):365-8. doi: 10.1258/095646207781024711.
citation: Gilson R, Nugent D, Werner RN, Ballesteros J, Ross J. 2019 IUSTI-Europe guideline for the management of anogenital warts. J Eur Acad Dermatol Venereol. 2020 Aug;34(8):1644-1653. doi: 10.1111/jdv.16522.
citation: Sazwi NN, Nalina T, Abdul Rahim ZH. Antioxidant and cytoprotective activities of Piper betle, Areca catechu, Uncaria gambir and betel quid with and without calcium hydroxide. BMC Complement Altern Med. 2013 Dec 11;13:351. doi: 10.1186/1472-6882-13-351.
citation: Pharm T, Hartini YS, Wahyuono S, Widyarini S, Yuswanto A. Hartini et al In vivo Immunomodulatory Effect and Histopathological Features of Mouse Liver and Kidney Treated with Neolignans Isolated from Red Betel (Piper crocatum Ruiz & Pav) Leaf. Tropical Journal of Pharmaceutical Research. 2014;13:1609-1614. doi:10.4314/tjpr.v13i10.6
citation: Bonin CM, Padovani CTJ, da Costa IP, Avila LS, Ferreira AMT, Fernandes CES, Dos Santos AR, Tozetti IA. Detection of regulatory T cell phenotypic markers and cytokines in patients with human papillomavirus infection. J Med Virol. 2019 Feb;91(2):317-325. doi: 10.1002/jmv.25312. Epub 2018 Sep 24.
citation: Xu Y, Zhu KJ, Zhu N, Jiang DH, Chen XZ, Cheng H. Expression of Foxp3+CD4+CD25+ regulatory T cells and Th1/Th2, Tc1/Tc2 profiles in the peripheral blood of patients with condyloma acuminatum. Clin Exp Dermatol. 2009 Mar;34(2):229-35. doi: 10.1111/j.1365-2230.2008.03001.x. Epub 2008 Dec 2.