Pain Induced by m-Cresol as Preservative

Официальное название

Pain Induced by m-Cresol as Preservative - A Randomised Controlled Crossover-Trial in Healthy Volunteers

Обзор

Preservatives such as m-Cresol are essential components in many subcutaneously injected medications, including insulin or human growth hormone, to prevent bacterial growth. However, clinical reports have suggested that these preservatives may cause local discomfort or pain at the injection site, which can negatively impact treatment adherence. While m-Cresol is widely used, its direct contribution to injection-site pain has not yet been investigated in a prospective clinical trial. This study aims to investigate whether subcutaneous injection of m-Cresol at concentrations commonly used in clinical practice (0.1% and 0.25%) cause significantly more pain than a preservative-free control solution. In a randomized, double-blind crossover design, healthy volunteers will receive three separate injections in a belly fold. Participants will rate their pain every 5 seconds until it subsides. The findings will help determine if m-Cresol is a primary source of injection-site pain and could lead to the development of more comfortable drug formulations.

Подробное описание

Background and Objective:

m-Cresol has been used since 1980 to limit bacterial growth in parenteral medications. Although it is generally considered safe, evidence for local side effects has appeared in case reports and a clinical trial where changing the preservative led to a disappearance of local discomfort. This suggests that the preservative itself, rather than the active drug or the pH of the solution, may be responsible for a pain sensation. The objective of this study is to systematically evaluate if subcutaneous injection of m-Cresol at clinically relevant concentrations causes pain in humans.

Study Design:

This is a randomized, double-blind, placebo-controlled, 3-period crossover trial in healthy volunteers (n=18). To ensure an unbiased assessment and control for potential order effects, a Williams balanced design is utilized for the randomization of treatment sequences.

Methodology:

Familiarization: Participants first receive an unblinded injection of control solution to become accustomed to the experimental procedure and the numerical pain rating scale.

Interventions: Subjects receive three randomized, double-blind 300 µl subcutaneous injections at different spots on a belly fold, separated by at least 3 cm. The treatments include:

1. m-Cresol at 0.1% 2. m-Cresol at 0.25% 3. Control solution. Pain Assessment: For each injection, pain intensity is recorded every 5 seconds using a numerical pain rating scale (0-100) until no pain is reported for 30 consecutive seconds. The pain caused by the needle insertion itself is rated separately before the injection begins to serve as a covariate for the statistical analysis.

Statistical Analysis:

The primary endpoint is the Area Under the Curve (AUC) of the subjective pain ratings over time. Comparisons will be made between the different m-Cresol concentrations and the vehicle control using a linear mixed model to test the primary hypotheses.

Вмешательства

• Другое m-Cresol 0.1%
  A preservative administered subcutaneously at 0.1%, a common concentration used in medicines.
• Другое m-Cresol 0.25%
  A preservative administered subcutaneously at 0.25%, a common concentration used in medicines.
• Другое Control Solution
  A control solution administered subcutaneously.

Первичные конечные точки

• Area Under the Curve (AUC) of Pain Intensity [Срок оценки: From injection start until pain subsides (approximately 15-60 seconds per injection).]

Критерии участия

Критерии включения

• Age between 18 and 70 years
• Full legal capacity Exclusion criteria
• Participant of another study, ongoing or within the last four weeks
• Current medication intake (except hormonal contraception) or drug abuse
• Female subjects: Positive pregnancy test or breastfeeding
• Body temperature above 38°C, verified by infrared thermometer
• Known allergic diseases, in particular asthmatic disorders and skin diseases
• Sensory deficit, skin disease or hematoma of unknown origin in the examination of the test site

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Распределение

Рандомизированное

Модель

Перекрёстный дизайн

Маскирование

Тройное слепое

Основная цель

Фундаментальное исследование

Центры проведения

Список центров уточняется — проверьте первичный протокол.

Идентификаторы

NCT: NCT07600814 · EK1688/2024

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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