Atorvastatin versus placebo for prevention of chronic migraine in adult patients

The primary objective of this multicentre, triple-blind, placebo-controlled, parallel-group 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, randomized, controlled study focusing on **chronic migraine**. This is clinically relevant as it aims to establish atorvastatin as a potential therapeutic option for chronic migraine, which could significantly impact patient management and treatment outcomes.

Secondary objectives include evaluating the number of responders to the treatment and assessing any side effects associated with atorvastatin use. These objectives are crucial for understanding the broader implications of atorvastatin therapy in terms of efficacy and safety in the chronic migraine population.

The clinical trial focuses on individuals diagnosed with **chronic migraine**, aiming to confirm the preventative effects of Atorvastin. 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 at least one year prior to inclusion, with the condition starting before the age of 50. Eligible individuals must have had at least 15 headache days per month, with a minimum of 8 being migraine days, as confirmed by a headache diary. The trial excludes those using other migraine prophylactics during the study. Women of child-bearing potential must not be pregnant or planning pregnancy and are required to use highly effective contraception. The sponsor has not provided information regarding the total number of participants. The selection process ensures a diverse group without targeting any vulnerable populations, and lifestyle factors such as diet and physical activity are not specified as part of the selection criteria.

The clinical trial is designed as a **randomized**, triple-blind, placebo-controlled, parallel-group study to evaluate the efficacy and safety of **atorvastatin** in individuals with chronic migraine. The trial will commence on May 13, 2024, with an estimated completion date of December 31, 2028. Participants will be randomly assigned to receive either atorvastatin 40 mg daily or a placebo, administered orally, over a maximum treatment period of 21 days for atorvastatin and 12 days for the placebo. 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 the change in the number of headache days, the number of reported side effects, and a cost comparison between the two treatment groups.

Study visits will follow a structured sequence, beginning with an inclusion (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. The screening visit will also involve obtaining informed consent. Follow-up visits will be scheduled to monitor the participants' adherence to the treatment regimen, assess the occurrence of any adverse events, and collect data on migraine and headache frequency. The end-of-study visit will conclude the trial, during which final assessments will be conducted, and participants will be debriefed.

Participant involvement is expected to last for the duration of the treatment period, with additional time allocated for follow-up assessments. Conditions that may lead to early termination from the study include non-compliance with the study protocol, the occurrence of significant adverse events, or withdrawal of consent by the participant. The trial aims to confirm the preventative effects of atorvastatin observed in smaller studies and to provide comprehensive data on its efficacy and safety in a larger population with chronic migraine.

The clinical trial involves the administration of **atorvastatin**, a chemical substance classified under the ATC code C10AA05. Atorvastatin is provided in a pharmaceutical form identified as PHF2355, and it is administered orally. The maximum daily dose of atorvastatin is 40 mg, with a total maximum dose of 84 mg over a treatment period of 21 days. Participants are required to adhere to the dosing schedule, and compliance will be monitored throughout the trial to ensure accurate data collection and analysis.

In addition to atorvastatin, a **placebo** is utilized as a comparator in this study. The placebo is formulated as a film-coated tablet and is also administered orally. The maximum daily dose for the placebo is one tablet, with a total maximum dose of 84 tablets over a 12-day treatment period. The placebo serves as a control to evaluate the efficacy of atorvastatin in the prevention of chronic migraine. Participant adherence to the placebo regimen will be monitored to maintain the integrity of the trial results.

The efficacy of **atorvastatin** in the treatment of chronic migraine will be assessed in a multicentre, triple-blind, placebo-controlled, parallel-group study. The primary endpoint for evaluating efficacy is the difference between the 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 in the change from baseline in the number of days with headache, the number of reported side effects in both the placebo and atorvastatin groups, and a comparison of costs associated with the treatment, considering the price of the medicine, acute medication, and lost worktime.

Data collection will involve the use of headache diaries to confirm the frequency of migraine days before randomization to treatment. The study will ensure that participants meet the inclusion criteria, such as having at least 15 headache days per month, with at least 8 being migraine days, as confirmed by the headache diary. The trial is designed to confirm the preventative effect of atorvastatin observed in smaller studies on episodic migraine, now applied to a larger cohort with chronic migraine. The trial is scheduled to start recruitment on May 1, 2024, with an estimated end date of December 31, 2028.