A phase Ib/II clinical study to evaluate the safety and efficacy of topical Arnica tincture to treat non-complicated Cutaneous Leishmaniasis in Colombia

BackgroundCutaneous leishmaniasis (CL) is caused by Leishmania parasites and affects 1.2 million cases annually, mainly in the Americas and the Eastern Mediterranean region. The standard treatment with pentavalent antimonials is often limited by its toxicity, prompting the search for alternative therapies. Arnica montana L. (Asteraceae) is a well-known phytotherapeutic plant with anti-inflammatory properties, traditionally used to treat bruises, sprains, distortions, and inflammation caused by insect bites. In our previous work, Arnica tincture (AT) obtained from the flowers showed excellent in vitro activity against Leishmania and in vivo activity in a golden hamster model of CL. It also demonstrated high skin permeability and retention in the epidermis without systemic circulation, making it a promising option for topical treatment of CL. MethodsWe conducted a randomized, open-label, phase Ib-II clinical trial. Adults with parasitologically confirmed uncomplicated CL were randomly assigned to receive AT topically, 3 times daily, for either 30 or 45 days. We assessed therapeutic response and monitored safety by recording adverse events at each follow-up visit. All adverse events were graded according to the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0. ResultsSixteen subjects were enrolled, with eight assigned to each treatment regimen. Twelve participants completed the 180-day follow-up, all achieved complete lesion healing (100% cure rate). Four participants withdrew their informed consent before or during treatment. The most common adverse events were mild and included erythema, pain, edema, and a burning sensation at the application site. No severe adverse effects were reported. ConclusionAT showed promising results in treating CL and had a favorable safety profile. Due to the small sample size and lack of comparison with standard therapies, further studies with more robust methodologies are needed to confirm these findings. Trial registration: NCT05094908 Author SummaryCutaneous leishmaniasis (CL) is a parasitic skin disease affecting over a million people annually, primarily in tropical and subtropical regions. Current treatments rely on pentavalent antimonials, which are often associated with severe side effects and limited accessibility in endemic communities. Seeking safer alternatives, we explored the use of a topical tincture derived from Arnica montana, a medicinal plant known for its anti-inflammatory properties. Previous studies have demonstrated the efficacy of this formulation against Leishmania parasites in laboratory and animal models, along with high skin retention and low systemic absorption, which are key characteristics for a topical therapeutic. We conducted a phase Ib/II clinical trial in Colombia to assess the safety and therapeutic response of Arnica tincture in adults with parasitologically confirmed, uncomplicated CL (NCT05094908). Participants were randomized to receive treatment for either 30 or 45 days. Of the 16 individuals enrolled, 12 completed the full 180-day follow-up, and all achieved complete lesion healing. No severe adverse effects were reported; only mild, localized reactions such as erythema or burning were observed. Our findings suggest that AT may be a safe and effective topical alternative for treating CL. Although these results are promising, further clinical trials with larger populations and comparison to standard treatments are necessary to confirm its efficacy and potential role in public health strategies.