Effects of Low-dose Aspirin in Bipolar Disorder: Study Protocol for a Randomised Controlled Trial (the A-Bipolar RCT)

Introduction: Accumulating data support the association between increased inflammation and bipolar disorder (BD), and preliminary data suggest that augmentation with low-dose aspirin (LDA) may protect against the onset and deterioration of BD via anti-inflammatory pathways. The A-bipolar randomised controlled trial (RCT) aims to investigate whether adding LDA to standard treatment improves day-to-day mood instability (MI) in BD.

Methods And Analysis: A two-arm, triple-blind, parallel-group, superiority RCT including 250 patients with newly diagnosed BD treated at the Copenhagen Affective Disorder Clinic, Denmark. Participants are randomised 1:1 to either 150 mg of acetylsalicylic acid daily (LDA) or a placebo for six months in addition to their regular treatment. Mood instability, calculated from daily smartphone-based mood evaluations, is the primary outcome measure due to its internal validity as a real-life measure for patients and external validity as it reflects patients' illness severity and functioning. Analyses will be conducted as intention-to-treat analyses using a linear mixed model including time (categorical) and the time-treatment interaction as fixed effects and with an unstructured covariance pattern to account for repeated measurements on each study participant. The trial is Good Clinical Practice monitored.

Ethics And Dissemination: The Danish Research Ethics Committee (H-21014515) and the data agency, Capital Region of Copenhagen (P-2021-576) approved the trial. Results will be published in peer-reviewed journals.

Trial Registration Number: NCT05035316.