An Early Phase 1 interventional study of m-Cresol 0.1% and m-Cresol 0.25% in Pain, Acute Pain and Healthy Volunteer Study, sponsored by Medical University of Vienna. Not yet recruiting. Open to participants aged 18 Years to 70 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2026-05-22.
Sponsored by Medical University of Vienna · Early Phase 1, Interventional, and Basic science
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.
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:
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.
2,219 studies on the registry are indexed under Pain; 917 are open to participants now.
This study's planned enrollment of 18 is below the median of 70 across 1,904 interventional studies indexed under Pain.
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Inclusion criteria
Participants receive a 300 µl subcutaneous injection of m-Cresol at a concentration of 0.1%.
Other: m-Cresol 0.1%
Participants receive a 300 µl subcutaneous injection of m-Cresol at a concentration of 0.25%.
Other: m-Cresol 0.25%
Participants receive a 300 µl subcutaneous injection of control solution.
Other: Control Solution
A preservative administered subcutaneously at 0.1%, a common concentration used in medicines.
A preservative administered subcutaneously at 0.25%, a common concentration used in medicines.
A control solution administered subcutaneously.
Area Under the Curve (AUC) of Pain Intensity
Total pain burden calculated as the Area Under the Curve of serial pain ratings (0-100 numerical pain rating scale) recorded every 5 seconds from the start of injection until no pain is reported for 30 seconds.
Time frame: From injection start until pain subsides (approximately 15-60 seconds per injection).
No study locations are listed for this record.
Plan to share: Yes — De-identified individual participant data (IPD), including pain ratings, time-stamped injection responses, and basic demographics (age, sex), will be shared alongside the publication of the primary results. Only data used in the main publication and relevant supplementary analyses will be included.
Supporting information: Study protocol, Sap, Analytic code
No publications or documents are linked to this record.
This study is not yet recruiting, as verified in May 2026. You cannot join it, but the record below documents what was studied.
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Medical University of Vienna