SchizophreniaNCT00567281
Bilateral Repetitive Transcranial Magnetic Stimulation for Auditory Hallucinations Original Study
A study testing Magstim Rapid 2 system triggering Magstim Super Rapid system and Magstim Rapid-2 system triggering Magstim Super Rapid system in people with Schizophrenia, run by Yale University at 1 site in United States.
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… Read more about this study
- Who is it for?
- Ages 18 to 55 years
- Conditions the study is for
- Schizophrenia
- What is being tested?
- Magstim Rapid 2 system triggering Magstim Super Rapid system and Magstim Rapid-2 system triggering Magstim Super Rapid system
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2007to Sep 2012
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Previously enrolled in our "parent" rTMS trial with passage of at least six months since last received active rTMS
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Department of Psychiatry, Yale School of Medicine
New Haven, Connecticut, 06519
About this study
Official title: Bilateral rTMS Clinical Trial for Persistent Auditory Hallucinations Original Study
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.
Read the 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.
- Conditions
- Schizophrenia
- Being tested
- Magstim Rapid 2 system triggering Magstim Super Rapid system, Magstim Rapid-2 system triggering Magstim Super Rapid system
- 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
- Medical subject headings
- Schizophrenia, Psychotic Disorders, Hallucinations
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Magstim Rapid 2 system triggering Magstim Super Rapid systemDevice
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 systemDevice
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.
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Active bilateral rTMS to left/right Wernicke's area and opposite side middle temporal gyrus Receives: Device: Magstim Rapid 2 system triggering Magstim Super Rapid system |
| 2 | Active comparator | Active rTMS to left/right Wernicke's region plus sham rTMS to opposite hemisphere middle temporal cortex Receives: Device: Magstim Rapid-2 system triggering Magstim Super Rapid system |
What is being measured
The primary outcome is the main question the study is designed to answer.
Hallucination change score
Measured: Measured at every week over a total 4 weeks
Clinical Global Improvement Scale
Measured: Measured at every week over a total of 4 weeks
Frequency subscale of Auditory Hallucinations Rating Scale
Measured: Measured at baseline and every week over a total of 4 weeks
Secondary outcomes (5)
Summed scores of Auditory Hallucination Rating Scale
Measured: Measured at baseline and every week over a total of 4 weeks
PANSS composite positive symptoms scale
Measured: Measured at baseline and every week over a total of 4 weeks
PANSS composite negative symptom scale
Measured: Measured at baseline and every week over a total of 4 weeks
PANSS total score
Measured: Measured at baseline and every week over a total of 4 weeks
California Verbal Learning Test (CVLT)
Measured: Measured at baseline and every week over a total of 4 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Dec 2007 (estimated)
- Study startOct 2007
- Primary completionSep 2012
- Study completionSep 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for SchizophreniaStudies of the same condition, open and under way.
- More trials run by Yale UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Device feasibility
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Outcomes assessor
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- Yale University
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Responsible party
- Sponsor
- Investigators
- Ralph Hoffman, MD, Principal investigator, Yale University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00567281
- Sponsor's protocol ID
- 0409027023_a
- Other IDs
- R01MH073673-02, NARSAD, 2R01MH067073
- Status last verified
- Sep 2020
- First submitted
- 3 Dec 2007
- Last updated
- 17 Sep 2020
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 15936729Hoffman 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.
PubMed 10744097Hoffman 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.
PubMed 17298962Hoffman 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.
PubMed 18978327
Study at a glance
From the registry record, last updated by the sponsor on 17 Sep 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Bilateral rTMS Clinical Trial for Persistent Auditory Hallucinations Original Study
- ClinicalTrials.gov ID
- NCT00567281
- Acronym / sponsor ID
- 0409027023_a
- Conditions
- Schizophrenia
- Keywords
- Schizoaffective disorder, Auditory Hallucinations, Voices, Repetitive Transcranial Magnetic Stimulation, rTMS, Wernicke's Area, Middle Temporal Cortex, Persistent Auditory Hallucinations
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- Yale UniversityUniversity, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Study start
- Oct 2007
- Primary completion
- Sep 2012 (actual)
- Study completion
- Sep 2012 (actual)
- First posted
- 4 Dec 2007 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Device feasibility
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Device: Magstim Rapid 2 system triggering Magstim Super Rapid systemActive bilateral rTMS to left/right Wernicke's area and opposite side middle temporal gyrus |
| 2 | Active comparator | Device: Magstim Rapid-2 system triggering Magstim Super Rapid systemActive rTMS to left/right Wernicke's region plus sham rTMS to opposite hemisphere middle temporal cortex |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (1 listed)
- Previously enrolled in our "parent" rTMS trial with passage of at least six months since last received active rTMS
Key exclusion criteria (4 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Magstim Rapid 2 system triggering Magstim Super Rapid systemWeek 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. | Device | 1 |
| Magstim Rapid-2 system triggering Magstim Super Rapid systemWeek 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. | Device | 2 |
Primary outcome
Hallucination change score
Time frame: Measured at every week over a total 4 weeks
Clinical Global Improvement Scale
Time frame: Measured at every week over a total of 4 weeks
Frequency subscale of Auditory Hallucinations Rating Scale
Time frame: Measured at baseline and every week over a total of 4 weeks
5 secondary outcomes
Summed scores of Auditory Hallucination Rating Scale
Time frame: Measured at baseline and every week over a total of 4 weeks
PANSS composite positive symptoms scale
Time frame: Measured at baseline and every week over a total of 4 weeks
PANSS composite negative symptom scale
Time frame: Measured at baseline and every week over a total of 4 weeks
PANSS total score
Time frame: Measured at baseline and every week over a total of 4 weeks
California Verbal Learning Test (CVLT)
Time frame: Measured at baseline and every week over a total of 4 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Sep 2020.
- Background: PubMed 15936729Hoffman 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.
- Background: PubMed 10744097Hoffman 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.
- Background: PubMed 17298962Hoffman 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.
- Background: PubMed 18978327Hoffman 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.
- Click here for a description of rTMS trials of auditory hallucinations at YaleLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ralph Hoffman, MD principal investigator
Yale University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Magstim Rapid 2 system triggering Magstim Super Rapid system and Magstim Rapid-2 system triggering Magstim Super Rapid system in people with Schizophrenia, run by Yale University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 17 Sep 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Hallucination change score (time frame: Measured at every week over a total 4 weeks). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00567281, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Sep 2020.