Efficacy of Transdermal Capsaicin 8% Versus Low-Dose Capsaicin 0.04% in Neuropathic Pain-Associated Digital Osteoarthritis: A Randomized Controlled Trial

The primary objective of this study is to compare the **effectiveness** at 8 weeks (W8) of the transdermal application of capsaicin 8% to that of a control (low dose capsaicin at 0.04%) on finger pain in patients with painful digital **osteoarthritis** with a neuropathic pain component. This is clinically relevant as it aims to determine the efficacy of a higher concentration of capsaicin in alleviating pain associated with digital osteoarthritis, potentially offering a more effective treatment option for patients suffering from this condition.

Secondary objectives include:

• Comparing the effectiveness at W8 of the transdermal application of capsaicin 8% to that of capsaicin 0.04% on various parameters such as functional disability, quality of life, anxiety and depression, the number of arthralgias and clinical synovitis, the intensity of pain concerning the most painful finger, disease activity according to the patient, the percentage of improvement in pain in the most painful finger, the "Patient Global Impression of Change" (PGIC) global improvement score, painful symptoms of osteoarthritis, the level of ultrasensitive C-reactive protein (CRPus), the value of inflammatory and cartilage degradation biomarkers, and the consumption of analgesics and anti-inflammatories.
• Evaluating the tolerance of the treatment.
• Studying the effect of transdermal application of capsaicin 8% on the weekly evolution of pain compared to transdermal application of capsaicin 0.04%.
• Comparing the effectiveness at 16 weeks (W16) of two transdermal applications of capsaicin 8% (eight weeks apart) to a single transdermal application of capsaicin 8% on finger pain.

The clinical trial involves participants diagnosed with **digital osteoarthritis**, focusing on individuals experiencing finger pain with a neuropathic component. The study population includes both male and female subjects aged 18 years and older. Participants are required to have a diagnosis of digital osteoarthritis as per the American College of Rheumatology criteria and must report finger pain intensity of at least 40 mm on a Visual Analogue Scale (VAS). The trial does not involve a vulnerable population. Participants were selected based on their inadequate response, adverse effects, or contraindications to traditional analgesics and NSAIDs. Women of childbearing age are required to use effective contraception throughout the trial. The sponsor has not provided information regarding the total number of participants in the study.

The clinical trial is designed to evaluate the effectiveness of **capsaicin** in the treatment of **digital osteoarthritis**. This study is a randomized, double-blind, controlled trial comparing the transdermal application of capsaicin 8% to a control group receiving a low dose of capsaicin at 0.04%. The primary objective is to assess the reduction in finger pain intensity at eight weeks, measured on a Visual Analog Scale (VAS) ranging from 0 to 100 mm. The trial is expected to commence recruitment on May 31, 2024, and conclude by October 31, 2027.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, diagnosis of digital osteoarthritis, and the presence of neuropathic pain. Following successful screening, participants will be randomized to receive either the capsaicin 8% patch or the control patch. The study involves regular follow-up visits to monitor safety and efficacy, with the primary endpoint being evaluated at the eight-week mark. The end-of-study visit will occur after the completion of the treatment period, where final assessments will be conducted.

The expected duration of participant involvement is approximately eight weeks, with conditions for early termination including adverse effects, withdrawal of consent, or non-compliance with study procedures. Participants are required to adhere to the study protocol, including the use of effective contraception for women of childbearing age throughout the trial. The trial is conducted under strict ethical guidelines, ensuring the safety and well-being of all participants.

The clinical trial involves the use of two treatments to evaluate their effectiveness in managing pain associated with digital **osteoarthritis**. The experimental medication is the **Qutenza 179 mg cutaneous patch**, which contains the active substance **capsaicin**. This pharmaceutical form is a cutaneous patch designed for **cutaneous use**. The patch is applied transdermally, allowing the active ingredient to be absorbed through the skin. The maximum daily dose is 25,600 mg/m², and the treatment period is limited to one day. The patch is manufactured by **GRÜNENTHAL GMBH** and is authorized for use in the European Union under the marketing authorization number EU/1/09/524/001. The **ATC code** for capsaicin is N01BX04, indicating its classification as a topical analgesic.

The comparator treatment in this study is a low-dose capsaicin formulation, specifically **capsaïcine 0.04%**. This formulation is also intended for cutaneous use, although specific details regarding its pharmaceutical form, dosage, and administration route are not provided. This low-dose capsaicin serves as the control treatment in the trial, allowing for a comparative analysis of its effectiveness against the higher-dose Qutenza patch. The study aims to assess the impact of these treatments on finger pain in patients with painful digital osteoarthritis, particularly focusing on those with a neuropathic pain component. Participant compliance with the treatment regimen will be monitored throughout the study to ensure accurate and reliable results.

Efficacy in the clinical trial titled "Capsaicin in digital osteoarthritis versus control: a randomized study" will be assessed by comparing the effectiveness of transdermal application of **capsaicin** 8% to a control (low dose capsaicin at 0.04%) on finger pain in patients with painful digital osteoarthritis with a neuropathic pain component. The primary endpoint for evaluating efficacy is the intensity of finger pain at eight weeks (W8), measured using a Visual Analog Scale (VAS) ranging from 0 to 100 mm. This scale is a validated tool commonly used in clinical settings to quantify pain intensity, providing a reliable measure of patient-reported outcomes. The trial is designed to objectively assess the reduction in pain intensity, which is a critical parameter for determining the therapeutic benefit of the treatment under investigation.