Clinical Trial: Repetitive Transcranial Magnetic Stimulation (rTMS) of the Insula for Treatment of Alcohol Addiction

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: Repetitive Transcranial Magnetic Stimulation (rTMS) of the Insula for Treatment of Alcohol Addiction

Brief Summary: The purpose of this study is to investigate the effects of repetitive transcranial magnetic stimulation (rTMS) targeting the insula on alcohol use and neural responses in alcohol-dependent patients.

Detailed Summary:

Objectives: To investigate the effects of repetitive transcranial magnetic stimulation (rTMS) targeting the insula on alcohol use and neural responses in alcohol-dependent patients.

Study population: Treatment seeking alcohol dependent subjects (N=82), aged 18-65 years, who have first completed standard alcohol withdrawal treatment if needed.

Design: This is a double-blind, sham-controlled randomized study, comprising three phases. Participants will be hospitalized during the first two of these, and will be outpatients during the third. During Phase 1 the study (screening; up to 14 days), participants will undergo a set of baseline assessments; this phase will conclude with consent, inclusion and randomization. During Phase 2 (treatment; appr. 3 weeks, with at least the first week being hospitalized), participants will first undergo an MRI scan to collect resting state and structural data, and will then receive one of two treatments: Active (10Hz) rTMS; or sham stimulation, both targeting the insula bilaterally. rTMS sessions will be conducted five times per week, for 3 weeks, for a total of 15 sessions. Stimulation will be with an H-coil designed to reach deeper structures such as the insula. A second MRI scan will be obtained at the end of this phase to assess changes in resting state connectivity, and to evaluate insula activity in tasks known to activate this structure. In addition, a lumbar puncture will be carried out at the end of this phase to assess possible effects on central neurotransmitter and growth factor levels, as indexed in the cerebrospinal fluid. For Phase 3 (follow-up, lasting 12 weeks), patients will be followed as outpatients for 12 weeks, with clinic visits at weeks 1, 2, 4, 8 and 12 post discharge; measures of alcohol use will be collected during this phase.

  • Heavy Drinking [ Time Frame: 12 weeks follow-up from treatment completion ]
    Reduction in heavy alcohol use during the outpatient follow-up phase (%heavy drinking days) measured by standard Time-Line Follow-Back methodology
  • Insula activity [ Time Frame: Within 5 days of treatment completion ]
    Insula activity (%signal change, as measured by fMRI BOLD), during a task known to be associated with insula responses, risky decision making


    • Original Primary Outcome: Same as current

    Current Secondary Outcome:

    • BOLD responses in a battery of standard fMRI tasks that probe processing of alcohol-associated cues, reward function, and emotional responses. [ Time Frame: Within 5 days after the last TMS session ]
    • Alterations in resting-state connectivity of the insula with other nodes in the putative Salience Network (SN), executive control network (ECN) and the default-mode network (DMN) by rTMS. [ Time Frame: Within 5 days after the last TMS session ]
    • Objective biomarkers of alcohol use [ Time Frame: 12 weeks follow-up from treatment completion ]
      Gamma-glutamyl transferase (GGT); carbohydrate deficient transferrin (CDT); ethyl glucuronide (EtG) in urine and hair.
    • Alcohol craving and psychiatric symptoms [ Time Frame: 12 weeks follow-up from treatment completion ]
      Measured by the Penn Alcohol Craving Scale (PACS), mood and anxiety symptoms, as measured using the respective subscales of the Comprehensive Psychiatric Rating Scale (CPRS) and Clinical Global Impression (CGI).
    • Smoking [ Time Frame: 12 weeks follow-up from treatment completion ]
      Measured by urine cotinine / creatinine ratios.


    Original Secondary Outcome: Same as current

    Information By: Linkoeping University

    Dates:
    Date Received: December 21, 2015
    Date Started: November 2015
    Date Completion: December 2017
    Last Updated: December 28, 2015
    Last Verified: December 2015