Bilateral Repetitive Transcranial Magnetic Stimulation for Auditory Hallucinations Original Study

Schizophrenia Clinical Trial

Official title:

Bilateral rTMS Clinical Trial for Persistent Auditory Hallucinations Original Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00567281
• Other study ID #: 0409027023_a
• Secondary ID: R01MH073673-02NA
• Status: Completed
• Phase: N/A
• Start date: October 2007
• Est. completion date: September 2012

Study information

• Verified date: September 2020
• Source: Yale University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: September 2012
• Est. primary completion date: September 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

Inclusion Criteria:

• Previously enrolled in our "parent" rTMS trial with passage of at least six months since last received active rTMS

Exclusion Criteria:

• Active substance abuse or alcohol abuse

• Pregnancy

• Dose or type of psychiatric medication changed within the 4 weeks prior to study entry

• Recent head trauma, seizures, or significant unstable medical condition

Related Conditions & MeSH terms

• Hallucinations
• Schizophrenia

Intervention

Device:
• Magstim Rapid 2 system triggering Magstim Super Rapid system
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.
• Magstim Rapid-2 system triggering Magstim Super Rapid system
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.

Locations

Country	Name	City	State
United States	Department of Psychiatry, Yale School of Medicine	New Haven	Connecticut

Sponsors (2)

Lead Sponsor	Collaborator
Yale University	National Institute of Mental Health (NIMH)

Country where clinical trial is conducted

United States, 

References & Publications (4)

Hoffman RE, Anderson AW, Varanko M, Gore JC, Hampson M. Time course of regional brain activation associated with onset of auditory/verbal hallucinations. Br J Psychiatry. 2008 Nov;193(5):424-5. doi: 10.1192/bjp.bp.107.040501. — View Citation

Hoffman RE, Boutros NN, Hu S, Berman RM, Krystal JH, Charney DS. Transcranial magnetic stimulation and auditory hallucinations in schizophrenia. Lancet. 2000 Mar 25;355(9209):1073-5. — View Citation

Hoffman RE, Gueorguieva R, Hawkins KA, Varanko M, Boutros NN, Wu YT, Carroll K, Krystal JH. Temporoparietal transcranial magnetic stimulation for auditory hallucinations: safety, efficacy and moderators in a fifty patient sample. Biol Psychiatry. 2005 Jul 15;58(2):97-104. — View Citation

Hoffman RE, Hampson M, Wu K, Anderson AW, Gore JC, Buchanan RJ, Constable RT, Hawkins KA, Sahay N, Krystal JH. Probing the pathophysiology of auditory/verbal hallucinations by combining functional magnetic resonance imaging and transcranial magnetic stimulation. Cereb Cortex. 2007 Nov;17(11):2733-43. Epub 2007 Feb 13. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Hallucination change score		Measured at every week over a total 4 weeks
Primary	Clinical Global Improvement Scale		Measured at every week over a total of 4 weeks
Primary	Frequency subscale of Auditory Hallucinations Rating Scale		Measured at baseline and every week over a total of 4 weeks
Secondary	Summed scores of Auditory Hallucination Rating Scale		Measured at baseline and every week over a total of 4 weeks
Secondary	PANSS composite positive symptoms scale		Measured at baseline and every week over a total of 4 weeks
Secondary	PANSS composite negative symptom scale		Measured at baseline and every week over a total of 4 weeks
Secondary	PANSS total score		Measured at baseline and every week over a total of 4 weeks
Secondary	California Verbal Learning Test (CVLT)		Measured at baseline and every week over a total of 4 weeks

External Links

•   Click here for a description of rTMS trials of auditory hallucinations at Yale