SchizophreniaNCT03544333
Boost rTMS for Auditory Verbal Hallucinations
A study testing transcranial magnetic stimulation in people with Schizophrenia and Auditory Hallucination, run by Northwell Health at 1 site in United States.
Trial summary
This is a randomized, placebo controlled, double-blind clinical trial. The investigators aim to examine the safety and efficacy of repeated transcranial magnetic stimulation (rTMS) for the treatment of auditory verbal hallucinations (AVH) in patients with schizophrenia who are not taking antipsychotic medication. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Schizophrenia, Auditory Hallucination
- What is being tested?
- transcranial magnetic stimulation
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 5 participants
- Where
- 1 siteUnited States
- Study dates
- 16 Apr 2018to 22 Jan 2019
- 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 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Provision of signed and dated informed consent form
- Stated willingness to comply with all study procedures and availability for the duration of the study
- Male or female, aged 18 to 65
- Diagnosed with Diagnostic and Statistical Manual (DSM) V diagnosis of schizophrenia (295.90), schizoaffective disorder (295.70), or brief psychotic disorder (298.80), prone to AVH in the acute phases of the disorder
- Willing to adhere to the rTMS regimen
- No antipsychotic medication in the last two weeks prior to the start of the study as well as no antipsychotic medication during participation in the study
- Agreement to adhere to Lifestyle Considerations throughout study duration
Who cannot join
- Current use of antipsychotic medication within the last 2 weeks
- Electroconvulsive therapy or rTMS within three months (see the TMS screening questionnaire)
- History of seizures
- Presence of implanted electronic device or metal implant in the head and neck region (DBS, cochlear implant, etc.)
- Pregnancy, as assessed with a pregnancy test prior to every MRI measurement, or lactation
- Any active general medical condition or central nervous system disease which can affect cognition or response to treatment
Show all 9Show fewer
- Treatment with another investigational drug or other intervention within 2 weeks
- Current diagnosis of delirium, dementia, or amnestic amnesiac disorder; Diagnosis of mental retardation; Current (within the past three months) diagnosis of active substance dependence, or active substance abuse within the past week as indicated by self-report.
- Patients who are cognitively impaired and are thus not able to give informed consent
Trial locations and contacts
1 site in 1 country.
United States1 site
The Zucker Hillside Hospital, Northwell Health
Manhasset, New York, 11004
About this study
Official title: Boost rTMS for AVH - Therapeutic Response and Neurobiological Prediction Markers in Auditory Verbal Hallucinations
This is a randomized, placebo controlled, double-blind clinical trial. The investigators aim to examine the safety and efficacy of repeated transcranial magnetic stimulation (rTMS) for the treatment of auditory verbal hallucinations (AVH) in patients with schizophrenia who are not taking antipsychotic medication. The investigators employ a novel, accelerated protocol with only four sessions of low-frequency rTMS in one day. The effects of this accelerated protocol will be compared to the sham stimulation. Additionally, the investigators will examine the effects of rTMS on a neurophysiological level by evaluating mechanism of action in the temporo-parietal lobe by means of functional magnetic resonance imaging.
Read the detailed description
Auditory verbal hallucinations affect up to 70% of schizophrenia patients (Waters, 2012), yet, even extended antipsychotic medication does not ameliorate AVH in 20-30% of patients (Sukhwinder S Shergill et al., 2007) and is often accompanied by side effects (Leucht et al., 2009). Therefore, it is crucial to develop and assess promising potentially beneficial therapeutic options.
Non-invasive brain stimulation techniques like repetitive transcranial magnetic stimulation (rTMS) have been proposed to disrupt mechanisms in question. A number of meta-analyses (Aleman, Sommer, \& Kahn, 2007; Demeulemeester et al., 2012; Freitas, Fregni, \& Pascual-Leone, 2009; C. W. Slotema, Blom, van Lutterveld, Hoek, \& Sommer, 2014; C. W. Slotema, Dirk Blom, Hoek, \& Sommer, 2010; Tranulis, Sepehry, Galinowski, \& Stip, 2008) found significant effect sizes ranging from 0.42 to 1.04 for 1Hz rTMS over the left temporo-parietal junction for the treatment of AVH. However, the majority of studies so far investigated the effects of rTMS in treatment resistant schizophrenia patients as an ad-on or second-line treatment.
No study to date has explored the effects of rTMS either as a first-line treatment or in the initial stage of the illness. This is surprising, considering the fact that rTMS is a safe treatment with minimal side-effects (Rossi, Hallett, Rossini, \& Pascual-Leone, 2009) that could be used already in the earlier phase of treatment. This stands in considerable contrast to the range of side-effects associated with antipsychotics (Leucht et al., 2017) that can be disabling for patients and lead to lower quality of life.
Therefore, the crucial next step is (1) to explore the effects of rTMS in medication-free patients from the whole schizophrenia spectrum and (2) to use an accelerated protocol of multiple rTMS-sessions within a short period of time. To make this assessment feasible, considering that patients have to be off medication, the safest and also most efficient way is an accelerated rTMS protocol. The great advantage of such an approach is that the effects of rTMS can be investigated independently of potentially influencing effects of antipsychotics and at the same time assess the efficacy of rTMS within a very short amount of time.
In the proposed study, the investigators aim to determine the efficacy of rTMS as a potential treatment for AVH in schizophrenia and thus reduce suffering in patients and their relatives.
- Conditions
- Schizophrenia, Auditory Hallucination
- Being tested
- transcranial magnetic stimulation
- Keywords
- transcranial magnetic stimulation (TMS), brain stimulation, medication-free
- Medical subject headings
- Schizophrenia, Hallucinations
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
transcranial magnetic stimulationDevice
We will assess safety and efficacy of the following protocol: 1Hz of rTMS over the Sylvian parietal temporal area (area Spt) four times on 1 day (1 pulse/second and a total of 1'000 pulses: 16 minutes' protocol at 100 % of motor threshold modified based on Hoffman et al., 1999). Area Spt will be localized via baseline structural imaging and our Localite TMS navigation system.
| Study group | Role | What they receive |
|---|---|---|
| real transcranial magnetic stimulation | Experimental | In the treatment arm, patients will receive 1Hz of repetitive transcranial magnetic stimulation (rTMS) over the left Sylvian parietal temporal area (area Spt) four times on 1 day (1 pulse/second and a total of 1'000 pulses: 16 minutes' protocol at 100 % of motor threshold modified based on Hoffman et al.,1999). Area Spt will be localized via baseline structural imaging and our Localite TMS navigation system. Receives: Device: transcranial magnetic stimulation |
| sham transcranial magnetic stimulation | Placebo comparator | In the comparator arm, patients will receive no stimulation. The TMS coil adjusted to the patients head will not be plugged into the TMS machine and can thus not have an effect on the brain. Yet, patients will hear the same noises from a coil that is plugged in, see the TMS machine running, and area Spt localized via baseline structural imaging and our Localite TMS navigation system. Receives: Device: transcranial magnetic stimulation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Efficacy of Transcranial Magnetic Stimulation for Auditory Verbal Hallucinations Assessed With the Hallucination Change Scale
Examine change in AVH severity, measured with the Hallucination Change Scale, due to low-frequency rTMS.
The Hallucination Change Scale is a self-rating assesses severity of hallucinations. It is anchored at baseline using the patient's description of AVH for the previous 24-hours which is assigned a score of 10. The subsequent assessments are in relation to the baseline where a reduction of AVH relates to a value < 10 (best being a value of 0) and a worsening of AVH relates to a value > 10 (twice as severe as baseline being a value of 20).
Measured: Four timepoints of the Hallucination Change Scale (after every TMS session). Here, score after final session is reported.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Jun 2018
- Study start16 Apr 2018
- Primary completion22 Jan 2019
- Study completion22 Jan 2019
Why it stopped: Because of low recruitment numbers.
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.
- Other trials for SchizophreniaStudies of the same condition, open and under way.
- 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 5 participants (actual)
Sponsor and investigators
- Lead sponsor
- Northwell Health
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Philipp Homan, Northwell Health
- Investigators
- Philipp Homan, MD PhD, Principal investigator, Zucker Hillside Hospital, New York City, USA.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03544333
- Sponsor's protocol ID
- 18-0024
- Status last verified
- Apr 2021
- First submitted
- 27 Apr 2018
- Last updated
- 5 May 2021
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 5 May 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Boost rTMS for AVH - Therapeutic Response and Neurobiological Prediction Markers in Auditory Verbal Hallucinations
- ClinicalTrials.gov ID
- NCT03544333
- Acronym / sponsor ID
- 18-0024
- Conditions
- Schizophrenia, Auditory Hallucination
- Keywords
- transcranial magnetic stimulation (TMS), brain stimulation, medication-free
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Because of low recruitment numbers.
- Enrolment
- 5 participants (actual)
- Lead sponsor
- Northwell HealthUniversity, hospital or other
- Study start
- 16 Apr 2018 (actual)
- Primary completion
- 22 Jan 2019 (actual)
- Study completion
- 22 Jan 2019 (actual)
- First posted
- 1 Jun 2018 (actual)
- Results
- Posted 5 May 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a randomized, placebo controlled, double-blind clinical trial. The investigators aim to examine the safety and efficacy of repeated transcranial magnetic stimulation (rTMS) for the treatment of auditory verbal hallucinations (AVH) in patients with schizophrenia who are not taking antipsychotic medication. The investigators employ a novel, accelerated protocol with only four sessions of low-frequency rTMS in one day. The effects of this accelerated protocol will be compared to the sham stimulation. Additionally, the investigators will examine the effects of rTMS on a neurophysiological level by evaluating mechanism of action in the temporo-parietal lobe by means of functional magnetic resonance imaging.
Detailed description
Auditory verbal hallucinations affect up to 70% of schizophrenia patients (Waters, 2012), yet, even extended antipsychotic medication does not ameliorate AVH in 20-30% of patients (Sukhwinder S Shergill et al., 2007) and is often accompanied by side effects (Leucht et al., 2009). Therefore, it is crucial to develop and assess promising potentially beneficial therapeutic options.
Non-invasive brain stimulation techniques like repetitive transcranial magnetic stimulation (rTMS) have been proposed to disrupt mechanisms in question. A number of meta-analyses (Aleman, Sommer, \& Kahn, 2007; Demeulemeester et al., 2012; Freitas, Fregni, \& Pascual-Leone, 2009; C. W. Slotema, Blom, van Lutterveld, Hoek, \& Sommer, 2014; C. W. Slotema, Dirk Blom, Hoek, \& Sommer, 2010; Tranulis, Sepehry, Galinowski, \& Stip, 2008) found significant effect sizes ranging from 0.42 to 1.04 for 1Hz rTMS over the left temporo-parietal junction for the treatment of AVH. However, the majority of studies so far investigated the effects of rTMS in treatment resistant schizophrenia patients as an ad-on or second-line treatment.
No study to date has explored the effects of rTMS either as a first-line treatment or in the initial stage of the illness. This is surprising, considering the fact that rTMS is a safe treatment with minimal side-effects (Rossi, Hallett, Rossini, \& Pascual-Leone, 2009) that could be used already in the earlier phase of treatment. This stands in considerable contrast to the range of side-effects associated with antipsychotics (Leucht et al., 2017) that can be disabling for patients and lead to lower quality of life.
Therefore, the crucial next step is (1) to explore the effects of rTMS in medication-free patients from the whole schizophrenia spectrum and (2) to use an accelerated protocol of multiple rTMS-sessions within a short period of time. To make this assessment feasible, considering that patients have to be off medication, the safest and also most efficient way is an accelerated rTMS protocol. The great advantage of such an approach is that the effects of rTMS can be investigated independently of potentially influencing effects of antipsychotics and at the same time assess the efficacy of rTMS within a very short amount of time.
In the proposed study, the investigators aim to determine the efficacy of rTMS as a potential treatment for AVH in schizophrenia and thus reduce suffering in patients and their relatives.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| real transcranial magnetic stimulation | Experimental | Device: transcranial magnetic stimulationIn the treatment arm, patients will receive 1Hz of repetitive transcranial magnetic stimulation (rTMS) over the left Sylvian parietal temporal area (area Spt) four times on 1 day (1 pulse/second and a total of 1'000 pulses: 16 minutes' protocol at 100 % of motor threshold modified based on Hoffman et al.,1999). Area Spt will be localized via baseline structural imaging and our Localite TMS navigation system. |
| sham transcranial magnetic stimulation | Placebo comparator | Device: transcranial magnetic stimulationIn the comparator arm, patients will receive no stimulation. The TMS coil adjusted to the patients head will not be plugged into the TMS machine and can thus not have an effect on the brain. Yet, patients will hear the same noises from a coil that is plugged in, see the TMS machine running, and area Spt localized via baseline structural imaging and our Localite TMS navigation system. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Provision of signed and dated informed consent form
- Stated willingness to comply with all study procedures and availability for the duration of the study
- Male or female, aged 18 to 65
- Diagnosed with Diagnostic and Statistical Manual (DSM) V diagnosis of schizophrenia (295.90), schizoaffective disorder (295.70), or brief psychotic disorder (298.80), prone to AVH in the acute phases of the disorder
- Willing to adhere to the rTMS regimen
Key exclusion criteria (9 listed)
- Current use of antipsychotic medication within the last 2 weeks
- Electroconvulsive therapy or rTMS within three months (see the TMS screening questionnaire)
- History of seizures
- Presence of implanted electronic device or metal implant in the head and neck region (DBS, cochlear implant, etc.)
- Pregnancy, as assessed with a pregnancy test prior to every MRI measurement, or lactation
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 |
|---|---|---|
| transcranial magnetic stimulationWe will assess safety and efficacy of the following protocol: 1Hz of rTMS over the Sylvian parietal temporal area (area Spt) four times on 1 day (1 pulse/second and a total of 1'000 pulses: 16 minutes' protocol at 100 % of motor threshold modified based on Hoffman et al., 1999). Area Spt will be localized via baseline structural imaging and our Localite TMS navigation system. | Device | real transcranial magnetic stimulation, sham transcranial magnetic stimulation |
Primary outcome
Efficacy of Transcranial Magnetic Stimulation for Auditory Verbal Hallucinations Assessed With the Hallucination Change Scale
Time frame: Four timepoints of the Hallucination Change Scale (after every TMS session). Here, score after final session is reported.
Examine change in AVH severity, measured with the Hallucination Change Scale, due to low-frequency rTMS. The Hallucination Change Scale is a self-rating assesses severity of hallucinations. It is anchored at baseline using the patient's description of AVH for the previous 24-hours which is assigned a score of 10. The subsequent assessments are in relation to the baseline where a reduction of AVH relates to a value < 10 (best being a value of 0) and a worsening of AVH relates to a value > 10 (twice as severe as baseline being a value of 20).
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 May 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Philipp Homan, MD PhD principal investigator
Zucker Hillside Hospital, New York City, USA.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing transcranial magnetic stimulation in people with Schizophrenia and Auditory Hallucination, run by Northwell Health 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 7 inclusion and 9 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 5 May 2021. 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. Some participants in this study may receive a placebo. 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 5 May 2021). 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?
Efficacy of Transcranial Magnetic Stimulation for Auditory Verbal Hallucinations Assessed With the Hallucination Change Scale (time frame: Four timepoints of the Hallucination Change Scale (after every TMS session). Here, score after final session is reported.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 5 May 2021.