A multicentre, triple blind, placebo controlled, parallel group study of atorvastatin in chronic migraine

The primary objective of this study is to evaluate whether the favorable preventative effect of **atorvastatin** observed in three smaller studies on episodic migraine can be confirmed in a larger multicenter, randomized, controlled study focusing on **chronic migraine**. This is clinically relevant as it aims to establish the efficacy of atorvastatin as a preventative treatment for chronic migraine, potentially offering a new therapeutic option for patients suffering from this debilitating condition.

Secondary objectives include evaluating the number of responders to the treatment and assessing any side effects associated with the use of atorvastatin in this patient population. These objectives are crucial for understanding the overall safety and effectiveness profile of atorvastatin in the context of chronic migraine management.

The clinical trial focuses on individuals diagnosed with **chronic migraine**, aiming to confirm the preventative effects of Atorvastin observed in previous studies. The study population includes both male and female participants aged between 18 and 65 years. Participants are required to have experienced the onset of migraines before the age of 50 and must have had migraines for at least one year prior to inclusion. They should have at least 15 headache days per month, with a minimum of 8 being migraine days, as confirmed by a headache diary. The trial excludes individuals using other migraine prophylactics and requires women of child-bearing potential to use highly effective contraception and not be pregnant or planning pregnancy during the study. The sponsor has not provided the total number of participants involved in the trial. The selection process ensures a non-vulnerable population, with no specific lifestyle considerations such as diet or physical activity mentioned.

The clinical trial is designed to evaluate the efficacy and safety of **atorvastatin** in the treatment of chronic migraine. This is a multicenter, triple-blind, placebo-controlled, parallel-group study. Participants will be randomly assigned to receive either atorvastatin 40 mg or a placebo, administered orally in the form of film-coated tablets. The trial is expected to last until December 31, 2028, with recruitment starting on April 1, 2023. The maximum treatment period for each participant is 12 months, with a daily dose of one tablet.

The study will include several visits, beginning with a screening visit to confirm eligibility based on criteria such as age (18 to 65 years), a history of chronic migraine according to ICHD-3 criteria, and the absence of other migraine prophylactics. Participants must have experienced at least 15 headache days per month, with at least 8 being migraine days, in the three months prior to inclusion. This frequency will be verified through a headache diary before randomization. Follow-up visits will occur at regular intervals to monitor the number of migraine and headache days, as well as any side effects. The primary endpoint is the difference in the change from baseline in the number of migraine days per four weeks between the atorvastatin and placebo groups. Secondary endpoints include changes in the number of headache days, reported side effects, and a cost comparison between the two treatment groups.

The end-of-study visit will assess the overall outcomes and gather final data. Participants may be withdrawn from the study if they do not adhere to the protocol, experience significant adverse effects, or choose to withdraw consent. The trial aims to confirm the preventative effects of atorvastatin observed in smaller studies on episodic migraine, now applied to a larger cohort with chronic migraine.

The clinical trial involves the administration of **Atorvastatin**, marketed as Atorvastatin Pensa 40 mg film-coated tablets. This experimental medication is formulated as a film-coated tablet and is intended for **oral use**. Each tablet contains 40 mg of the active substance atorvastatin, which is of chemical origin. The dosing regimen for this trial specifies a maximum daily dose of one tablet, with a total maximum dose of 84 tablets over a treatment period of 12 weeks. The administration schedule is designed to ensure consistent daily intake, and participant compliance will be monitored throughout the study duration.

In addition to the experimental medication, a **placebo** is utilized as a comparator treatment in this study. The placebo is also presented in the form of a film-coated tablet, identical in appearance to the atorvastatin tablets, to maintain the blinding of the study. The placebo tablets are administered orally, following the same dosing schedule as the atorvastatin, with a maximum daily dose of one tablet and a total maximum dose of 84 tablets over the 12-week treatment period. The use of a placebo is critical in evaluating the efficacy of atorvastatin in the prevention of chronic migraine, as it allows for a controlled comparison against the active treatment.

Efficacy in this clinical trial will be assessed by evaluating the primary and secondary endpoints. The primary endpoint is the difference between groups receiving **atorvastatin** 40 mg daily and placebo in the change from baseline in the number of migraine days per 4 weeks. Secondary endpoints include the difference between these groups in the change from baseline in the number of days with headache, the number of reported side effects, and a comparison of costs associated with the treatment, considering the price of the medicine, acute medication, and lost worktime.

The trial is designed as a multicentre, triple-blind, placebo-controlled, parallel-group study. The efficacy parameters will be collected and analyzed at specified intervals throughout the study duration, which is planned to last up to 12 months. The data collection will involve patient-reported outcomes, likely through the use of headache diaries to confirm the frequency of migraine and headache days before randomization and during the treatment period. The analysis will focus on comparing the changes from baseline between the atorvastatin and placebo groups to determine the efficacy of atorvastatin in preventing chronic migraine.