Clinical trial NCT00567281: Bilateral Repetitive Transcranial Magnetic Stimulation for Auditory Hallucinations Original Study
Official title: Bilateral rTMS Clinical Trial for Persistent Auditory Hallucinations Original Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Schizophrenia
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
Lead sponsor: Yale University
Sponsor class: OTHER
Collaborators: name: National Institute of Mental Health (NIMH)
First posted: 2007-12-04
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: DEVICE_FEASIBILITY

Brief 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.

Eligibility criteria: 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

Primary outcomes:
measure: Hallucination change score
timeFrame: Measured at every week over a total 4 weeks
measure: Clinical Global Improvement Scale
timeFrame: Measured at every week over a total of 4 weeks
measure: Frequency subscale of Auditory Hallucinations Rating Scale
timeFrame: Measured at baseline and every week over a total of 4 weeks
Secondary outcomes:
measure: Summed scores of Auditory Hallucination Rating Scale
timeFrame: Measured at baseline and every week over a total of 4 weeks
measure: PANSS composite positive symptoms scale
timeFrame: Measured at baseline and every week over a total of 4 weeks
measure: PANSS composite negative symptom scale
timeFrame: Measured at baseline and every week over a total of 4 weeks
measure: PANSS total score
timeFrame: Measured at baseline and every week over a total of 4 weeks
measure: California Verbal Learning Test (CVLT)
timeFrame: Measured at baseline and every week over a total of 4 weeks
Other outcomes:
Locations:
city: New Haven
country: United States
facility: Department of Psychiatry, Yale School of Medicine
state: Connecticut
Study officials:
affiliation: Yale University
name: Ralph Hoffman, MD
role: PRINCIPAL_INVESTIGATOR
References:
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. doi: 10.1016/j.biopsych.2005.03.041.
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. doi: 10.1016/S0140-6736(00)02043-2.
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. doi: 10.1093/cercor/bhl183. Epub 2007 Feb 13.
citation: 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.