Arnica Tincture Fot the Treatment of Cutaneous Leishmaniasis II.

NCT06822478 | Recruiting Phase 3 DMC

• 1 other identifier: PEC01_2025
• Study Type: interventional
• Target: 96
• Locations: 1 country
• Sites: 1

Brief Summary

Cutaneous leishmaniasis (CL) is a parasitic disease caused by more than 20 different species of the protozoan parasite Leishmania. CL usually begins with a papule at the site of the sandfly bite, which enlarges to form a nodule that progresses to an ulceration, or a scaly or warty plaque, over a period of 1 to 3 months. The exact incidence of CL is not known. An estimated 1.2 million cases/year in approximately 100 countries worldwide suffer from different forms of CL. More than 90% of CL cases occur in the Americas and Eastern Mediterranean regions. Afghanistan, Algeria, Brazil, Colombia, Iraq, Pakistan, and Syria report more than 80% of new CL cases worldwide. Since 2010, the World Health Organization has insisted on the need to work on products that become alternatives for the treatment of LC, especially in products that can be applied topically because with them the probability of systemic toxicity is lower, increasing patient safety. Currently, it is recommended to apply local treatments for patients with localized LC, either with pentavalent antimonials administered intralesionally or with thermotherapy. Among the options for topical treatment are natural products that have been, are and will be of utmost importance as sources of medicinal agents. In addition to natural products that have found direct medicinal applications as pharmaceutical entities, many others can serve as chemical models or templates for the design, synthesis and semi-synthesis of novel substances for the treatment of human diseases. Arnica montana L. is a plant with anti-emollient, healing, anti-inflammatory, analgesic and antineuralgic properties; it is included in the Colombian vademecum of medicinal plants. In a randomized phase Ib/II clinical trial conducted in patients with localized LC in Colombia, 100% (per protocol analysis) and 92% (intention-to-treat analysis) efficacy was demonstrated, with no adverse effects other than those expected such as erythema, burning, pain or itching. By demonstrating that arnica tincture is effective and safe, and that A. montana flower extracts in different preparations (topical solutions, tinctures, liniments, ointments or gels) are approved by the European Medicines Agency and are included in the vademecum of Colombian plants issued by the Ministry of Social Protection of Colombia in 2008, the present study aims to establish the safety and efficacy of arnica tincture as an alternative for the topical treatment of localized LC compared to a currently available local therapeutic alternative: intralesional pentavalent antimonials.

Conditions

Leishmaniasis, Cutaneous

Keywords

Leishmaniasis; Cutáneo; Tintura de árnica

Outcome Measures

Primary Outcomes (1)

• Number of participants with healing (scarring) after treatment

  Defined as 100% epithelialization of the lesion (s) by day 90 post-treatment.

  day 90

Secondary Outcomes (1)

• Number of participants with Final post-treatment Healing

  day 105

Study Arms (2)

Regime 1. arnica tincture

EXPERIMENTAL

Regimen 1: tincture of arnica applied 3 times a day for 30 days. The participant applies the tincture in the morning, afternoon and evening, that is, three times a day.

Drug: Arnica Tincture

Regime 2 Pentavalent antimonials intralesionally.

ACTIVE COMPARATOR

Administered intralesionally. At a dose of 0.008 ml X mm of area of each lesion, maximum 15 ml in total, once a week for 5 weeks.

Drug: Meglumine antimoniate.

Interventions

Arnica Tincture DRUG

Arnika tincture is a topical plant-based preparation legally authorized in Colombia and in the countries of the European community, the product of this study is Arnika tinktur Gehrlicher (5249), manufactured by Gehrlicher Pharmazeutische Extrakte GmbH, Germany. According to the European Pharmacopoeia, the solution is a 70% hydroethanolic tincture prepared from the flowers of A. montana L, and composed at least 0.04% of sesquiterpene lactones. Arnica tincture will be applied topically by each participant on all lesions until day 30.

Also known as: topical solution

Regime 1. arnica tincture

Meglumine antimoniate. DRUG

Monotherapy with intralesional pentavalent antimonials is one of the treatments of care used for LC in Colombia and will be used as a comparator for safety evaluation. Pentavalent antimonials: administered intralesionally. At a dose of 0.008 ml X mm of area of each lesion, maximum 15 ml in total, once a week for 5 weeks.

Also known as: intralesionally, Pentavalent antimonials

Regime 2 Pentavalent antimonials intralesionally.

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• \. Males or females, over 12 years of age and adults without age limit. With a confirmed parasitological diagnosis of a primary infection of LC in at least one lesion, made by one of the following methods: 1) microscopic identification of amastigotes in the lesion tissue; 2) diagnosis of leishmania by PCR; 3) positive culture for promastigotes (Annex 2).
• \. With clinical diagnosis of localized LC. 4. Ulcer, nodule or plaque type lesions. Up to 9 lesions in total, and that the total area of all lesions is ≤1875 mm2 6. Subjects who have given written IC/Assent. 7. Subject is able to understand and comply with the requirements of the study. 8. Subjects who are able to attend the control visits.

You may not qualify if:

• Participants presenting one or more of the following criteria should be excluded from the study:
• Diagnosis or suspicion of mucosal/mucocutaneous, diffuse or disseminated Leishmaniasis or relapse or reactivation of an LC.
• Subjects with lesions involving the auricular region, orbital region, nasal region and/or labial region of the face, joints or in places that, in the opinion of the investigator, are difficult to apply topically or intralesionally to the study medication.
• History of clinically significant cardiovascular, renal, hepatic, hepatic, neurological or immunological diseases that may interact positively or negatively with the treatment.
• Having received treatment for Leishmaniasis or other treatment that, in the judgment of the investigator, may modify the course of infection with Leishmania in the last 8 weeks (56 days) prior to admission.
• Women with a positive pregnancy test during the screening process, or lactating, or women of childbearing age who do not agree to the use of contraceptives during treatment and until DPT45.
• Known or suspected history of hypersensitivity or idiosyncratic reactions to the investigational product or pentavalent antimonials in the trial.
• Subjects who are unwilling to attend study visits or who are unable to comply with follow-up visits for up to three months.

Sponsors & Collaborators

• Universidad de Antioquia: lead
• INNOVATION CORPORATION FOR THE DEVELOPMENT OF PRODUCTS FOR TROPICAL DISEASES (CIDEPRO): collaborator

Study Sites (1)

Grupo de Investigación Clínica PECET (GIC-PECET)

Medellín, Antioquia, 0004, Colombia

RECRUITING

Related Publications (20)

• Jurgens FM, Herrmann FC, Robledo SM, Schmidt TJ. Dermal Absorption of Sesquiterpene Lactones from Arnica Tincture. Pharmaceutics. 2022 Mar 29;14(4):742. doi: 10.3390/pharmaceutics14040742.

  PMID: 35456576 BACKGROUND

• Guidelines of the International Conference on Harmonization - Good Clinical Practice: Consolidated Guide (ICH E6), E6(R2) Current Step 4 version dated 9 November 2016

  BACKGROUND

• Iannitti T, Morales-Medina JC, Bellavite P, Rottigni V, Palmieri B. Effectiveness and Safety of Arnica montana in Post-Surgical Setting, Pain and Inflammation. Am J Ther. 2016 Jan-Feb;23(1):e184-97. doi: 10.1097/MJT.0000000000000036.

  PMID: 25171757 BACKGROUND

• Wagner S, Suter A, Merfort I. Skin penetration studies of Arnica preparations and of their sesquiterpene lactones. Planta Med. 2004 Oct;70(10):897-903. doi: 10.1055/s-2004-832613.

  PMID: 15490315 BACKGROUND

• Velasco-Castrejon O, Walton BC, Rivas-Sanchez B, Garcia MF, Lazaro GJ, Hobart O, Roldan S, Floriani-Verdugo J, Munguia-Saldana A, Berzaluce R. Treatment of cutaneous leishmaniasis with localized current field (radio frequency) in Tabasco, Mexico. Am J Trop Med Hyg. 1997 Sep;57(3):309-12. doi: 10.4269/ajtmh.1997.57.309.

  PMID: 9311641 BACKGROUND

• Lopez L, Robayo M, Vargas M, Velez ID. Thermotherapy. An alternative for the treatment of American cutaneous leishmaniasis. Trials. 2012 May 17;13:58. doi: 10.1186/1745-6215-13-58.

  PMID: 22594858 BACKGROUND

• Lee SA, Hasbun R. Therapy of cutaneous leishmaniasis. Int J Infect Dis. 2003 Jun;7(2):86-93. doi: 10.1016/s1201-9712(03)90002-6.

  PMID: 12839708 BACKGROUND

• Reveiz L, Maia-Elkhoury AN, Nicholls RS, Romero GA, Yadon ZE. Interventions for American cutaneous and mucocutaneous leishmaniasis: a systematic review update. PLoS One. 2013 Apr 29;8(4):e61843. doi: 10.1371/journal.pone.0061843. Print 2013.

  PMID: 23637917 BACKGROUND

• Alvar J, Velez ID, Bern C, Herrero M, Desjeux P, Cano J, Jannin J, den Boer M; WHO Leishmaniasis Control Team. Leishmaniasis worldwide and global estimates of its incidence. PLoS One. 2012;7(5):e35671. doi: 10.1371/journal.pone.0035671. Epub 2012 May 31.

  PMID: 22693548 BACKGROUND

• Votypka J, Kasap OE, Volf P, Kodym P, Alten B. Risk factors for cutaneous leishmaniasis in Cukurova region, Turkey. Trans R Soc Trop Med Hyg. 2012 Mar;106(3):186-90. doi: 10.1016/j.trstmh.2011.12.004. Epub 2012 Jan 26.

  PMID: 22284721 BACKGROUND

• Croft SL, Seifert K, Yardley V. Current scenario of drug development for leishmaniasis. Indian J Med Res. 2006 Mar;123(3):399-410.

  PMID: 16778319 BACKGROUND

• Velez I, Lopez L, Sanchez X, Mestra L, Rojas C, Rodriguez E. Efficacy of miltefosine for the treatment of American cutaneous leishmaniasis. Am J Trop Med Hyg. 2010 Aug;83(2):351-6. doi: 10.4269/ajtmh.2010.10-0060.

  PMID: 20682881 BACKGROUND

• Herwaldt BL. Leishmaniasis. Lancet. 1999 Oct 2;354(9185):1191-9. doi: 10.1016/S0140-6736(98)10178-2.

  PMID: 10513726 BACKGROUND

• Tiuman TS, Santos AO, Ueda-Nakamura T, Filho BP, Nakamura CV. Recent advances in leishmaniasis treatment. Int J Infect Dis. 2011 Aug;15(8):e525-32. doi: 10.1016/j.ijid.2011.03.021. Epub 2011 May 24.

  PMID: 21605997 BACKGROUND

• Almeida OL, Santos JB. Advances in the treatment of cutaneous leishmaniasis in the new world in the last ten years: a systematic literature review. An Bras Dermatol. 2011 May-Jun;86(3):497-506. doi: 10.1590/s0365-05962011000300012. English, Portuguese.

  PMID: 21738967 BACKGROUND

• Silva NS, Muniz VD. [Epidemiology of American tegumentary leishmaniasis in the State of Acre, Brazilian Amazon]. Cad Saude Publica. 2009 Jun;25(6):1325-36. doi: 10.1590/s0102-311x2009000600015. Portuguese.

  PMID: 19503963 BACKGROUND

• Soto J, Rea J, Balderrama M, Toledo J, Soto P, Valda L, Berman JD. Efficacy of miltefosine for Bolivian cutaneous leishmaniasis. Am J Trop Med Hyg. 2008 Feb;78(2):210-1.

  PMID: 18256415 BACKGROUND

• Blum J, Desjeux P, Schwartz E, Beck B, Hatz C. Treatment of cutaneous leishmaniasis among travellers. J Antimicrob Chemother. 2004 Feb;53(2):158-66. doi: 10.1093/jac/dkh058. Epub 2004 Jan 16.

  PMID: 14729756 BACKGROUND

• Blum J, Lockwood DN, Visser L, Harms G, Bailey MS, Caumes E, Clerinx J, van Thiel PP, Morizot G, Hatz C, Buffet P. Local or systemic treatment for New World cutaneous leishmaniasis? Re-evaluating the evidence for the risk of mucosal leishmaniasis. Int Health. 2012 Sep;4(3):153-63. doi: 10.1016/j.inhe.2012.06.004.

  PMID: 24029394 BACKGROUND

• Robledo SM, Velez ID, Schmidt TJ. Arnica Tincture Cures Cutaneous Leishmaniasis in Golden Hamsters. Molecules. 2018 Jan 12;23(1):150. doi: 10.3390/molecules23010150.

  PMID: 29329207 BACKGROUND

Related Links

• Common Terminology Criteria for Adverse Events (CTCAE)

MeSH Terms

Conditions

Leishmaniasis, Cutaneous; Leishmaniasis

Interventions

Arnicae flos extract; Solutions; Meglumine Antimoniate

Condition Hierarchy (Ancestors)

Euglenozoa Infections; Protozoan Infections; Parasitic Diseases; Infections; Skin Diseases, Parasitic; Vector Borne Diseases; Skin Diseases, Infectious; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Pharmaceutical Preparations; Meglumine; Sorbitol; Sugar Alcohols; Alcohols; Organic Chemicals; Hexosamines; Amino Sugars; Carbohydrates

Study Officials

• Iván D Velez, PhD

  Clinical research group -Program for Research and Control in Tropical Diseases GIC - PECET, Medellín, Antioquia

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Iván D Velez, PhD

CONTACT

+57(604)42196506; idvelez@pecet-colombia.org

Liliana Lopez, PhD

CONTACT

+5742196506; liliana.lopez@pecet-colombia.org

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: INVESTIGATOR
• Masking Details: The study was designed with a single-blind design where the investigator, who performs the role of efficacy evaluator, is unaware of the treatment arm to which the participant was assigned.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a single-center, single-blind, randomized, comparative study with two arms. After the informed consent process and verification of the eligibility criteria, volunteers will be randomly assigned to one of the interventions: 1: Arnica tincture, topical, with 3 applications per day for 30 days; 2: intralesional pentavalent antimonials for 5 weeks (1 application per week at a dose according to the lesion area). After initiation of treatment, a mid-treatment telephone or face-to-face follow-up will be performed depending on the treatment arm, in addition, follow-up visits will be made at the end of treatment (+ 7 days), day 45 post-treatment (+ 5 days) and day 90 post-treatment (+ 15 days) with an optional visit on day 105 post-treatment (+ 10 days), to evaluate the response to treatment and the safety of the treatment. The participant will keep a record of study medication application to document compliance with treatment and any symptoms experienced during treatment.

Study Record Dates

• First Submitted: February 6, 2025
• First Posted: February 12, 2025
• Study Start: March 11, 2026
• Primary Completion (Estimated): December 1, 2029
• Study Completion (Estimated): February 1, 2030
• Last Updated: April 2, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

CO (1)