Evaluation of Botulinum Toxin A on Gene Expression and Cellular Plasticity in Myogenous Temporomandibular Disorders

The primary objective of this study is to investigate whether treatment with **Botulinum Toxin A** (BTX) alters gene expressions, epigenetic signatures, and cellular plasticity in the masseter muscle of patients with myogenous temporomandibular disorders (TMDM). This is clinically relevant as it may provide insights into the molecular mechanisms underlying TMDM and the potential therapeutic effects of BTX, which could lead to improved treatment strategies for patients suffering from this condition.

Secondary objectives include assessing the effects of BTX on pain characteristics such as intensity, frequency, and sensibility, as well as other clinical variables in patients with TMDM. Additionally, the study aims to explore correlations between significantly changed expression of biomarkers and other clinical variables. These secondary objectives are important for understanding the broader impact of BTX treatment on patient symptoms and identifying potential biomarkers for treatment response.

The clinical trial focuses on **myogenous temporomandibular disorders (TMDM)**, specifically targeting a study population of females aged 20 to 45 years. The participants are selected based on a diagnosis of myalgia or myofascial pain with referral, as per the Diagnostic Criteria for Temporomandibular Disorders (DC/TMD) axis I. The trial includes individuals with a characteristic pain intensity greater than 40 out of 100 and those experiencing pain upon digital palpation of at least one of the masseter muscles. The study does not include male participants and involves a vulnerable population. The sponsor has not provided information regarding the total number of participants. Lifestyle factors such as diet, physical activity, or habits are not specified in the available data.

The clinical trial is designed to evaluate the effects of **botulinum toxin** on gene expressions, epigenetic signatures, and cellular plasticity in the masseter muscle of patients with **myogenous temporomandibular disorders** (TMDM). This is a Phase 4, randomized, double-blind, controlled trial, which aims to assess both the safety and efficacy of the treatment. The trial is expected to commence recruitment on October 9, 2023, and conclude by March 31, 2025. Participants will be randomly assigned to receive either the test product, botulinum toxin, or a comparator, which is a solution for injection/infusion. The administration route for both products is via intramuscular injection.

The study will involve several key visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as a diagnosis of myalgia or myofascial pain with referral, female gender aged 20-45 years, a characteristic pain intensity greater than 40/100, and pain upon digital palpation of at least one masseter muscle. Following the screening, participants will undergo treatment and attend follow-up visits to monitor changes in gene expressions, epigenetic signatures, and jaw muscle pain intensity. The primary endpoint is the change in gene expressions, epigenetic signatures, and cellular plasticity, while the secondary endpoint focuses on the change in jaw muscle pain intensity post-treatment.

The expected duration of participant involvement is approximately one month, corresponding to the maximum treatment period. Conditions that may lead to early termination from the study include non-compliance with the study protocol, adverse reactions to the treatment, or withdrawal of consent by the participant. The trial is not classified as low intervention, as it explores the safety and efficacy of a potential therapy for an existing product with marketing authorization. The study is conducted under strict regulatory guidelines to ensure the safety and well-being of all participants.

The clinical trial involves the administration of **Botulinum Toxin** as the experimental medication. This substance is provided in the form of a powder and solvent for solution for injection. The pharmaceutical form is identified as PHF00231MIG. The maximum daily dose is 100 U units, with a total maximum dose of 100 U units over the treatment period. The administration route is via **intramuscular injection**. The treatment period is limited to one day. The trial aims to assess the effects of Botulinum Toxin on gene expressions, epigenetic signatures, and cell plasticity in the masseter muscle of patients with temporomandibular disorder (TMD). Participant compliance will be monitored through standard clinical trial procedures.

The non-experimental treatment used in this study is a **solvent and diluting agent**, classified under the ATC code V07AB. This agent is provided as a solution for injection or infusion, with the pharmaceutical form designated as PHF00017MIG. The maximum daily and total dose is 1 ml millilitre, administered via intramuscular injection. This agent serves as a comparator in the trial, ensuring the effects of the experimental medication can be accurately assessed. The administration of this non-experimental treatment will follow the same compliance monitoring protocols as the experimental medication.

Efficacy in the clinical trial titled "Peripheral TMD Pain Mechanisms and the Effect by Botulinum Toxin A" will be assessed through both primary and secondary endpoints. The primary endpoint focuses on the change in gene expressions, epigenetic signatures, and cell plasticity in the masseter muscle of patients diagnosed with **Temporomandibular Disorders** (TMD). This will be evaluated to determine the biological impact of Botulinum Toxin A treatment on the muscle tissue at a molecular level.

The secondary endpoint involves measuring the change in jaw muscle pain intensity following treatment. This will provide insight into the clinical effectiveness of the intervention in reducing pain symptoms associated with TMD. The trial will utilize specific criteria for inclusion, such as a diagnosis of myalgia or myofascial pain with referral, female participants aged 20 to 45 years, a characteristic pain intensity greater than 40/100, and pain upon digital palpation of at least one of the masseter muscles. The trial is set to conclude by March 31, 2025, with recruitment having started on October 9, 2023.