Evaluation of Dantrolene Sodium in the Treatment of Darier Disease: A Randomized Clinical Trial

The primary objective of this clinical trial is to evaluate whether **dantrolene** treatment can reduce the skin area affected by **Darier disease**. This is clinically relevant as Darier disease is a chronic skin disorder characterized by wart-like blemishes on the body, and reducing the affected skin area could significantly improve patient outcomes and quality of life.

Secondary objectives include assessing whether dantrolene treatment can improve patient quality of life, mood, and treatment satisfaction; enhance skin condition; and affect skin quality on a microscopic and molecular level. Additionally, the study aims to evaluate the safety of dantrolene treatment in subjects with Darier disease and determine if a new disease severity scale can be effectively used for this condition.

The clinical trial focuses on evaluating the efficacy of dantrolene in reducing the skin area affected by **Darier disease**. The study population includes both male and female participants, aged 18 years and older, with no specific vulnerable populations selected. Participants were chosen based on a histopathologically verified diagnosis of Darier disease, characterized by typical skin symptoms such as hyperkeratotic papules and erythema, or a clinical diagnosis combined with a family history of the disease. The trial does not specify the total number of participants, as this information was not provided by the sponsor. Participants' general health status, lifestyle considerations such as diet and physical activity, and other habits were not detailed in the available data.

The clinical trial is designed to evaluate the efficacy of **dantrolene sodium** in reducing the skin area affected by **Darier disease**. This is a Phase 4, randomized, double-blind, controlled trial with an estimated duration from June 2022 to June 2026. The trial aims to assess the primary endpoint of a reduction in skin area using the 5-point Physician Global Assessment (PGA) scale, with a 20% reduction considered the minimal clinically important difference. Secondary endpoints include improvements in the Dermatological Quality of Life Index (DLQI), mood assessment using the Montgomery–Åsberg Depression Rating Scale (MADRS), and treatment satisfaction measured by the Treatment Satisfaction Questionnaire for Medication (TSQM). Additional assessments will utilize the Eczema Area and Severity Index (EASI) scale and Body Surface Area (BSA), alongside monitoring adverse events.

Participants will undergo a sequence of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on histopathologically verified diagnosis or clinical symptoms combined with family history. The inclusion criteria require a Physician Global Assessment of at least 3, written consent, and a minimum age of 18 years. Follow-up visits will be scheduled to monitor treatment progress, assess endpoints, and ensure participant safety. The end-of-study visit will conclude the trial, evaluating the overall outcomes and any long-term effects of the treatment.

The expected length of participant involvement is up to six months, corresponding to the maximum treatment period with **Dantrium Capsules 25mg**. Participants may be withdrawn from the study if they experience significant adverse reactions, fail to adhere to the study protocol, or withdraw consent. The trial is not classified as low intervention, and the therapeutic exploratory nature justifies its categorization. The trial is conducted under the sponsorship of Norgine Pharmaceuticals Limited, with the product administered orally in capsule form.

The clinical trial involves the use of **dantrolene sodium** as the experimental medication. The pharmaceutical form of the medication is a hard capsule, marketed under the name **Dantrium Capsules 25mg**. Each capsule contains 25 mg of the active substance, dantrolene sodium, which is chemically synthesized. The medication is administered orally, with a maximum daily dose of 100 mg. The total maximum dose over the course of the treatment is 17,150 mg. The treatment period is limited to a maximum of six months. The medication is manufactured by Norgine Pharmaceuticals Limited and is not a pediatric formulation. Participant compliance with the dosing schedule will be monitored throughout the trial.

No non-experimental treatments, such as standard-of-care therapy, placebo, or comparator treatments, are specified for use in this study. The trial is designed to evaluate the efficacy of dantrolene sodium in reducing the skin area affected by Darier disease. The study does not include any additional medications or interventions beyond the administration of the experimental drug.

Efficacy in the clinical trial of dantrolene for the treatment of **Darier disease** will be assessed using both primary and secondary endpoints. The primary endpoint is defined as a reduction in the skin area affected, measured by the 5-point Physician Global Assessment (PGA) scale. A reduction of 20% (equivalent to 1 point on the PGA scale) will be considered the minimal clinically important difference. Secondary endpoints include improvements in the Dermatological Quality of Life Index (DLQI), with a 4-point improvement deemed clinically significant. Additional assessments will involve the Montgomery–Åsberg Depression Rating Scale (MADRS) for mood evaluation and the Treatment Satisfaction Questionnaire for Medication (TSQM) to gauge treatment satisfaction. Complementary skin assessment tools such as the Eczema Area and Severity Index (EASI) scale and Body Surface Area (BSA) will also be utilized. The trial will monitor the number of adverse events and adverse reactions, both serious and non-serious, as part of the efficacy assessment. These parameters will be collected and analyzed at specified intervals throughout the trial duration to determine the therapeutic impact of dantrolene on patients with Darier disease.