Clinical Research Studies

The proposed study is a double-blind, 2-group randomized controlled trial designed to contrast acute and persisting effects of topiramate to those of placebo treatment in a sample of 150 participants with moderate to severe AUD comorbid with PTSD/subthreshold PTSD, and to evaluate the moderating effect of rs2832407 genotype on medication effects. Participants will be randomized in a 2:1 ratio to topiramate vs. placebo. Drug will be titrated to a maximum dose of 200 mg over 8 weeks, continued for 4 more weeks for a total of 12 weeks of treatment, and tapered over a 2-week period. We propose an integrative translational focus on alterations in excitatory and inhibitory signaling, focusing on GABA and glutamate and related circuitry, to model the neurobiology of AUD comorbid with PTSD/subthreshold PTSD and the mitigating effects of topiramate. We will study the behavioral, genetic, and plasma biomarker effects of topiramate vs. placebo in 150 participants with co-occurring AUD and PTSD/subthreshold and ascertain multi-modal imaging markers including structural MRI, task-based fMRI, and TMS evoked potentials in EEG. Imaging markers will be used to characterize excitatory and inhibitory circuits in the clinical trial participants with AUD+PTSD/subthreshold to determine predictors and mechanisms of topiramate vs. placebo treatment outcomes. Clinical interviews will be audio- taped to ensure clinical adherence and conduct interrater reliability. De-identified audio recordings of participants who consent to participate in the voicemarkers analysis will be encrypted and sent via secure sites for analysis. This project will advance our knowledge of personalized medicine for AUD comorbid with PTSD/subthreshold, with particular emphasis on understanding the mechanisms that account for the high variability in treatment outcomes for this comorbidity, how treatments like TPM are effective for certain individuals, and how best to identify those most likely to respond to TPM.