Bilateral Repetitive Transcranial Magnetic Stimulation for Auditory Hallucinations Original Study
Condition: Schizophrenia
MeSH terms: Hallucinations; Schizophrenia
Study type: Interventional

Summary: 
      This trial is designed to determine if administering repetitive transcranial magnetic
      stimulation (rTMS) simultaneously to two sites in the temporal lobes, one on the left and one
      on the right, produces greater improvements in "voices" and other symptoms of schizophrenia
      compared to rTMS given to just one site in the temporal lobes.
    

Detailed description: 
      This study is an extension of an ongoing clinical trial (ClinicalTrials.gov identifier NCT
      00308997) that was initiated in 2006. The primary objective of the ongoing clinical trial
      (hereafter called the "parent trial") is to determine efficacy of rTMS in curbing auditory
      hallucinations when delivered to a part of the left temporal lobe called Wernicke's area and
      a corresponding region in the right temporal lobe. The parent trial appears to show robust
      effects for active rTMS compared to effects of sham stimulation. However, observed responses
      following active rTMS have often been incomplete. Moreover, in some cases there has been a
      subsequent return of symptoms 1 to 6 months after the trial ended.

      We consequently have initiated a trial where patients who have participated in the parent
      trial and demonstrated an incomplete response or a subsequent return of symptoms may return
      to receive additional active rTMS. We hypothesize that efficacy of suppressive rTMS will be
      enhanced if directed simultaneously to right/left Wernicke's area (the site used in the
      parent trial) as well as to a second site located in the opposite middle temporal cortex.
      Roughly half of subjects in the re-enrollment will be randomized to receive active rTMS to
      right/left Wernicke's area plus active rTMS to opposite hemisphere middle temporal region,
      while half of subjects will be randomized to receive active rTMS to right/left Wernicke's
      area plus sham rTMS to opposite hemisphere middle temporal region. The position of the middle
      temporal regions will be determined by two recently completed brain imaging studies of
      auditory hallucinations suggesting that activation in these sites triggers auditory
      hallucinations. The two-position design will allow us to determine if active rTMS delivered
      to the middle temporal cortex is superior in amplifying efficacy of active rTMS targeting
      Wernicke's area and in reducing auditory hallucinations to sham stimulation to the same site.
      The re-enrollment protocol will utilize two rTMS devices simultaneously where one directly
      triggers the other.

      This study record has been amended to remove a third arm that was added in 2012. The third
      arm described was not actually a comparative arm, but rather an added objective with a
      different study population. Dr. Ralph Hoffman unexpectedly passed away while this study was
      being conducted. This study has been submitted as a separate study (NCT04548622) where the
      summarized study results of the terminated study will be presented.
    

Intervention name(s): Magstim Rapid 2 system triggering Magstim Super Rapid system; Magstim Rapid-2 system triggering Magstim Super Rapid system
Intervention type(s): Device; Device
Intervention description(s): Week 1 treatment includes rTMS for 5 sessions to either to left or right Wernicke's area (BA22) synchronous with rTMS to opposite hemisphere middle temporal cortex (BA21). Week 2 treatment includes rTMS given for 5 sessions with positions reversed (e.g., if Wernicke's stimulation was on the left during Week 1, position of rTMS will switch to the right side during Week 2 and vice-versa). As in Week 1, active rTMS will also be given synchronously to the opposite hemisphere middle temporal cortex. Weeks 3 and 4 include 10 stimulation sessions to the configuration of sites producing greater improvement in comparing results of Week 1 and Week 2. rTMS for each stimulation session will be given at 1-Hertz (once per second) for 16 minutes without interruption.; Week 1 includes repetitive rTMS for 5 sessions to either to left or right Wernicke's area (BA22) synchronous with sham rTMS to opposite hemisphere middle temporal cortex (BA21). Week 2 includes rTMS given for 5 sessions with positions reversed (e.g., if Wernicke's stimulation was on the left during Week 1, position of rTMS will switch to the right side during Week 2 and vice-versa). As in Week 1, sham rTMS will also be given synchronously to the opposite hemisphere middle temporal cortex. Weeks 3 and 4 include 10 stimulation sessions to the configuration of sites producing greater improvement in comparing results of Week 1 and Week 2. rTMS for each stimulation session will be given at 1-Hertz (once per second) for 16 minutes without interruption.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Outcomes Assessor)
Primary purpose: Device Feasibility
Keywords: Schizoaffective disorder; Auditory Hallucinations; Voices; Repetitive Transcranial Magnetic Stimulation; rTMS; Wernicke's Area; Middle Temporal Cortex; Persistent Auditory Hallucinations; Previously Participated in "Parent" rTMS Protocol