Arnica Tincture Fot the Treatment of Cutaneous Leishmaniasis

NCT05094908 | Active Not Recruiting Phase 1 DMC

• 1 other identifier: PEC02_2021
• Study Type: interventional
• Target: 16
• 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 generally begins with a papule at the sand fly bite site, increasing to form a nodule that progresses to ulceration, or a scaly or wart-like 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 around the world suffer from different forms of CL. In general, most lesions become ulcerated during the course of the disease. Among the different species of the parasite that cause LC, L. tropica from the Old World and L. braziliensis from the New World are considered the most important due to the severity of the disease they produce and because they are more difficult to cure with medications currently available. Since 2010, the World Health Organization has insisted on the need to work on products that become alternatives for the treatment of CL, especially in products that serve topical application because with them, the probability of systemic toxicity is lower , increasing patient safety. Among the options for topical treatment are natural products that have been, are, and will be extremely important as sources of medicinal agents. In addition to natural products that have found direct medicinal application 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-echemotic, healing, anti-inflammatory, analgesic and antineuralgic properties; It is included in the Colombian vademecum of medicinal plants. In previous studies it has been observed that the contact of the ulcerated skin with the product for up to 60 days does not generate toxic effects at the local level (application site) or at the systemic level, so it can be considered safe for use. To date there are no human studies with CL. Therefore, it is intended to evaluate the safety and tolerability of Arnica tincture in individuals with uncomplicated CL, by measuring the occurrence and severity analysis of local and systemic adverse events.

Conditions

Leishmaniasis, Cutaneous

Keywords

Leishmaniasis; Cutaneous; Arnica tincture

Outcome Measures

Primary Outcomes (1)

• Number of participants with Initial post-treatment healing

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

  day 90

Secondary Outcomes (2)

• Number of participants with Final post-treatment Healing

  day 180

• Number of participants with lesions that relapse

  day 180

Study Arms (2)

Regime 1 (30 days)

ACTIVE COMPARATOR

Regimen 1: arnica tincture applied 3 times a day for 30 days (group 1). For both regimens, the participant applies the tincture in the morning, afternoon and evening, that is, three times a day.

Drug: Arnica Tincture

Regime 2 (45 days)

ACTIVE COMPARATOR

Regimen 2 arnica tincture applied 3 times a day for 45 days (group 2). For both regimens, the participant applies the tincture in the morning, afternoon and evening, that is, three times a day.

Drug: Arnica Tincture

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 or 45, depending on the regimen to be evaluated.

Also known as: topical solution

Regime 1 (30 days); Regime 2 (45 days)

Eligibility Criteria

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

You may qualify if:

• Men or women, of legal age, between 18 and 65 years old.
• With a confirmed parasitological diagnosis of CL in at least one lesion, performed at least through the following methods: 1) microscopic identification of amastigotes in the lesion tissue; 2) diagnosis of leishmania through PCR; 3) positive culture for promastigotes.
• Subjects with an injury that meets the following criteria:
• Ulcer or nodule with a maximum size of 4 cm (the largest diameter).
• Not located in the ear, face, near mucous membranes, joints, or in places where, in the opinion of the IP, the administration of the product is difficult to apply topically.
• Subjects with a maximum of 4 LC lesions.
• Injury with an evolution of less than 4 months according to the subject's history.
• Subjects who have given their CI in writing.
• At the discretion of the IP, the subject is able to understand and comply with the requirements of the study.
• Subjects who can attend control visits.

You may not qualify if:

• Women with a positive pregnancy test during the screening process, or breastfeeding, or women of childbearing potential who do not accept the use of contraceptives during treatment and up to 45 days after treatment.
• History of clinically significant medical problems or treatments that may interact negatively or positively with topical treatment for Leishmaniasis, including any immunocompromising conditions.
• Within 8 weeks (56 days) of starting the study treatment, having received treatment for Leishmaniasis with any type of medication, including Glucantime that probably, in the opinion of the PI, could modify the course of infection with Leishmania.
• Based on physical examinations performed, a diagnosis of CML has been or is suspected.
• Known or suspected history of hypersensitivity or idiosyncratic reactions to study treatment.
• Present the following laboratory alterations:
• Serum creatinine above normal levels
• ALT / AST levels 3 times above the normal value (according to the levels reported by the local laboratory).
• Subjects who do not want to keep study appointments or who cannot keep follow-up visits for up to six months.

Sponsors & Collaborators

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

Study Sites (1)

Program for Research and Control in Tropical Diseases - PECET

Medellín, Antioquia, 0004, Colombia

Location

Related Publications (24)

• 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

• 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

• Management of Safety Information from Clinical Trials Report of CIOMS Working Group VI, Geneva 2005, Organizations of Medical Sciences (CIOMS) ISBN 92 9036 079 8

  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

• 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

• 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

• WHO technical report series; no. 949. Control of the leishmaniasis: report of a meeting of the WHO Expert Committee on the Control of Leishmaniases, Geneva, 22-26 March 2010

  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

• 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

• 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

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

  PMID: 10513726 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

• 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

• Pearson, R. D., A. De Queiroz Sousa, and S. M. B. Jeronimo. 2001. Leishmania species: visceral (kala-azar), cutaneous and mucosal leishmaniasis, p. 2831-2845. In G. L. Mandell, J. E. Bennett, and R. Dolin (ed.), Principles and practice of infectious diseases. Churchill Livingstone, New York, N.Y

  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

• 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

• 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

• 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

• 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

• 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

• 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

• Assessment report on Arnica montana L., flos, European Medicines Agency (Science medicines agency), 9 July 2013 EMA/HMPC/198794/2012 Committee on Herbal Medicinal Products (HMPC)

  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

• Robledo SM, Lopez L, Quintero J, Tabares Y, Garces AC, Rios-Echavarria S, Soto E, Velez ID, Schmidt TJ. A phase Ib/II clinical study to evaluate the safety and efficacy of topical Arnica tincture to treat non-complicated cutaneous leishmaniasis in Colombia. PLoS Negl Trop Dis. 2025 Aug 18;19(8):e0013123. doi: 10.1371/journal.pntd.0013123. eCollection 2025 Aug.

  PMID: 40825042 DERIVED

Related Links

• Ministry of Social Protection, 2008. Colombian Vademecum of Medicinal Plants
• Common Terminology Criteria for Adverse Events (CTCAE)
• Pan American Health Organization, PAHO. Leishmaniasis in the Americas: Recommendations for treatment. 2013

MeSH Terms

Conditions

Leishmaniasis, Cutaneous; Leishmaniasis

Interventions

Arnicae flos extract; Solutions

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

Study Officials

• Ivan D Velez, PhD

  Director PECET

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is an open, randomized, non-comparative, exploratory study with two arms. After the informed consent process and the verification of eligibility criteria, the volunteers will be randomly assigned to one of the interventions (30- or 45-day arnica tincture regimen) of the study. All individuals will have a telephone follow-up in the middle of the treatment, in addition, follow-up visits will be made at the end of the therapy, on day 45 post-treatment ± 5 days, on day 60 post-treatment ± 5 days (optional visit), on days 90 post-treatment ± 14 days and 180 days post-treatment-14 + 28 days to evaluate the therapeutic response. The participant will keep a record of the daily application (morning, afternoon and evening) of the study medication to document its application.

Study Record Dates

• First Submitted: September 28, 2021
• First Posted: October 26, 2021
• Study Start: May 3, 2023
• Primary Completion: November 2, 2024
• Study Completion: August 1, 2025
• Last Updated: February 10, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

CO (1)