SchizophreniaNCT04548622
Bilateral Repetitive Transcranial Magnetic Stimulation for Auditory Hallucinations Results
A study testing 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
The primary purpose of this study was to conduct fMRI neuroimaging studies prior to and subsequent to the rTMS intervention. The intent was to ascertain changes in regional brain activation and connectivity that most robustly predict level of improvement in auditory hallucinations elicited by bilateral rTMS as… 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
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2012to Oct 2016
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 Results for a Terminated Study
The primary purpose of this study was to conduct fMRI neuroimaging studies prior to and subsequent to the rTMS intervention. The intent was to ascertain changes in regional brain activation and connectivity that most robustly predict level of improvement in auditory hallucinations elicited by bilateral rTMS as assessed by the primary outcome variables.
Read the detailed description
This study is an extension of previous clinical trials (NCT00308997 and NCT00567281) that were initiated in 2006. This study record provides the results for the amended study NCT00567281 (originally called a 'third arm') that was discontinued following the passing of Dr. Ralph Hoffman. The primary purpose of the study was to conduct fMRI neuroimaging studies prior to and subsequent to the rTMS intervention. The intent was to ascertain changes in regional brain activation and connectivity that most robustly predict level of improvement in auditory hallucinations elicited by bilateral rTMS as assessed by our primary outcome variables. It was hoped that this combined fMRI/rTMS study would provide critical new insights into the neurobiological basis of auditory hallucinations.
The results presented are what was summarized following Dr. Hoffman's passing and were compiled by Dr. Philip Corlett.
- Conditions
- Schizophrenia
- Being tested
- 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 both the left and 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.
| Study group | Role | What they receive |
|---|---|---|
| Non-randomized bilateral rTMS | 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 |
What is being measured
The primary outcome is the main question the study is designed to answer.
PANSS Composite Positive Symptoms Hallucination Score
The Positive and Negative Syndrome Scale (PANSS) is a medical scale used for measuring symptom severity of patients with schizophrenia.The PANSS positive symptoms hallucinication score has a range of 1-7. Higher scores indicate more severe positive symptoms in patients with schizophrenia.
Measured: baseline to 4 weeks
PANSS Composite Negative Symptom Scale
The Positive and Negative Syndrome Scale (PANSS) is a medical scale used for measuring symptom severity of patients with schizophrenia.The PANSS negative scale has 7 Items, with a minimum score of 7 and a maximum score of 49. Higher scores indicate more severe negative symptoms in patients with schizophrenia.
Measured: baseline to 4 weeks
PANSS Total Score
The Positive and Negative Syndrome Scale (PANSS) is a medical scale used for measuring symptom severity of patients with schizophrenia.The PANSS total score has a minimum score of 30 and a maximum score of 210. Higher scores indicate more severe symptoms in patients with schizophrenia.
Measured: baseline to 4 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Sep 2020
- Study startSep 2012
- Primary completionOct 2016
- Study completionOct 2016
Why it stopped: Dr. Ralph Hoffman unexpectedly passed away.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- 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
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 15 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
- Philip Corlett, PhD, Principal investigator, Yale University Department of Psychiatry
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04548622
- Sponsor's protocol ID
- 0409027023_b
- Other IDs
- R01MH073673-02, NARSAD, 2R01MH067073
- Status last verified
- Oct 2020
- First submitted
- 4 Sep 2020
- Last updated
- 30 Oct 2020
- Results posted
- Yes, on ClinicalTrials.gov
- 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 30 Oct 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Bilateral rTMS Clinical Trial for Persistent Auditory Hallucinations Results for a Terminated Study
- ClinicalTrials.gov ID
- NCT04548622
- Acronym / sponsor ID
- 0409027023_b
- 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
- TerminatedReason stopped: Dr. Ralph Hoffman unexpectedly passed away.
- Enrolment
- 15 participants (actual)
- Lead sponsor
- Yale UniversityUniversity, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Study start
- Sep 2012
- Primary completion
- Oct 2016 (actual)
- Study completion
- Oct 2016 (actual)
- First posted
- 14 Sep 2020 (actual)
- Results
- Posted 30 Oct 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The primary purpose of this study was to conduct fMRI neuroimaging studies prior to and subsequent to the rTMS intervention. The intent was to ascertain changes in regional brain activation and connectivity that most robustly predict level of improvement in auditory hallucinations elicited by bilateral rTMS as assessed by the primary outcome variables.
Detailed description
This study is an extension of previous clinical trials (NCT00308997 and NCT00567281) that were initiated in 2006. This study record provides the results for the amended study NCT00567281 (originally called a 'third arm') that was discontinued following the passing of Dr. Ralph Hoffman. The primary purpose of the study was to conduct fMRI neuroimaging studies prior to and subsequent to the rTMS intervention. The intent was to ascertain changes in regional brain activation and connectivity that most robustly predict level of improvement in auditory hallucinations elicited by bilateral rTMS as assessed by our primary outcome variables. It was hoped that this combined fMRI/rTMS study would provide critical new insights into the neurobiological basis of auditory hallucinations.
The results presented are what was summarized following Dr. Hoffman's passing and were compiled by Dr. Philip Corlett.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Non-randomized bilateral rTMS | 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 |
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 both the left and 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 | Non-randomized bilateral rTMS |
Primary outcome
PANSS Composite Positive Symptoms Hallucination Score
Time frame: baseline to 4 weeks
The Positive and Negative Syndrome Scale (PANSS) is a medical scale used for measuring symptom severity of patients with schizophrenia.The PANSS positive symptoms hallucinication score has a range of 1-7. Higher scores indicate more severe positive symptoms in patients with schizophrenia.
PANSS Composite Negative Symptom Scale
Time frame: baseline to 4 weeks
The Positive and Negative Syndrome Scale (PANSS) is a medical scale used for measuring symptom severity of patients with schizophrenia.The PANSS negative scale has 7 Items, with a minimum score of 7 and a maximum score of 49. Higher scores indicate more severe negative symptoms in patients with schizophrenia.
PANSS Total Score
Time frame: baseline to 4 weeks
The Positive and Negative Syndrome Scale (PANSS) is a medical scale used for measuring symptom severity of patients with schizophrenia.The PANSS total score has a minimum score of 30 and a maximum score of 210. Higher scores indicate more severe symptoms in patients with schizophrenia.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Oct 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- 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.
Philip Corlett, PhD principal investigator
Yale University Department of Psychiatry
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 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: stopped early, as of the sponsor's last update on 30 Oct 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?
Yes. Results are posted in the registry (first posted 30 Oct 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
PANSS Composite Positive Symptoms Hallucination Score (time frame: baseline to 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 NCT04548622, 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 30 Oct 2020.