Auditory HallucinationSMA-AVHNCT04651621
SMA Targeted Magnetic Stimulation Against Auditory Verbal Hallucinations
A study testing continuous theta burst stimulation over the SMA in people with Auditory Hallucination, run by Uppsala University at 1 site in Sweden.
Trial summary
Auditory verbal hallucinations (AVH) are prevalent among patients with psychiatric disorders. Not only being highly stressful and functionally impairing, AVH often persist despite treatment. Read more about this study
- Who is it for?
- Ages 18 to 59 yearsHealthy volunteers can take part
- Conditions the study is for
- Auditory Hallucination
- What is being tested?
- continuous theta burst stimulation over the SMA
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 46 participants
- Where
- 1 siteSweden
- Study dates
- 2 Nov 2020to 8 Feb 2024
- 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 59 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Reported AVH with a minimum frequency of at least daily occurrence, with onset more than one month ago
- Stable psychopharmacological treatment past month
- Reporting no occurrences of AVH for the past year
- Stable psychopharmacological treatment past month
- No life-time occurrence of AVH
- No history of psychiatric disorders as assessed with a Mini-International Neuropsychiatric Interview (M.I.N.I.)
Who cannot join
- Ferromagnetic or electromagnetic implants that may pose a risk during magnetic resonance imaging (MRI) and/or cTBS
- A history of epilepsy
- Pregnancy
- Current substance use disorder or a history of alcohol use disorder as assessed with Alcohol Use Disorders Identification Test (AUDIT), Drug Use Disorders Identification Test (DUDIT), urine samples with test for illicit drugs and Phosphatidylethanol (PEth)
- Daily benzodiazepine use
- Factors that make the participant unlikely to be able to complete the study
Trial locations and contacts
1 site in 1 country.
Sweden1 site
Department of neuroscience, psychiatry, unit for Brain Stimulation and psychiatric clinical trials
Uppsala, 751 85
About this study
Auditory verbal hallucinations (AVH) are prevalent among patients with psychiatric disorders. Not only being highly stressful and functionally impairing, AVH often persist despite treatment. Recent attempts to treat AVH with add-on repetitive transcranial magnetic stimulation (rTMS) when targeting the temporoparietal junction (TPJ), a language node in the brain, has gained limited success. The aim of this investigation is to reduce AVH with rTMS using continous theta-burst stimulation over a novel target, the supplementary motor area (SMA), in participants with frequent AVH, while also assessing potential neurophysiological mechanisms underlying the symptom.
- Conditions
- Auditory Hallucination
- Being tested
- continuous theta burst stimulation over the SMA, sham continuous theta burst stimulation over the SMA
- Medical subject headings
- Hallucinations
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
continuous theta burst stimulation over the SMADevice
Each cTBS session consists of bursts of three pulses delivered with a rate of 50 Hz, with bursts repeated at a rate of 5 Hz for a total duration of 40 seconds, summing up to 600 pulses, 100% of motor threshold (MT) and applied over bilateral SMA. The target is located in the anterior-posterior direction over the transition between pre-SMA and SMA proper, (cortical point where a vertical line will pass through the anterior commissure). The center of a figure-of-eight coil will be placed over the target, guided with neuronavigation equipment that utilizes the anatomical brain image from the pre-cTBS scanning session.
sham continuous theta burst stimulation over the SMADevice
The same stimulation parameters but a concealed sham coil will be used with only superficial magnetic stimulation to mimic the sensation of the active stimulation
| Study group | Role | What they receive |
|---|---|---|
| Open label active cTBS | Experimental | Four consecutive days with 40s cTBS, 100% MT over the SMA, five times a day with 50 minutes between stimulations Receives: Device: continuous theta burst stimulation over the SMA |
| active cTBS | Experimental | One test session with 40s active cTBS, 100% MT, over the SMA in the initial double blind cross-over phase Receives: Device: continuous theta burst stimulation over the SMA |
| Sham cTBS | Sham comparator | One test session with 40s sham cTBS, 100% MT, over the SMA in the initial double blind cross-over phase with a special sham coil that diverts the magnetic field to be only superficial Receives: Device: sham continuous theta burst stimulation over the SMA |
What is being measured
The primary outcome is the main question the study is designed to answer.
Amplitude on EEG in speech-listen task
Neurophysiological outcome of the blinded cross-over phase
Measured: 5-30 minutes after intervention
Change on The Psychotic Symptom Rating Scales (PSYRATS)
Auditory Verbal Hallucination symptom interview, total score
Measured: 1 day after completion of open treatment phase
Secondary outcomes (6)
Finger tapping test
Computerized version of the finger tapping test from The Halstead-Reitan Neuropsychological Test Battery, performance
Measured: 5-30 minutes after intervention
Double step saccade-task
Performance (Zimmermann et al Sci Rep, 2018).
Measured: 20-60 minutes after intervention
Resting state functional magnetic resonance imaging (rsfMRI)
Resting state SMA connectivity change as measured with fMRI
Measured: 1 day after completion of open treatment phase
Magnetic resonance spectroscopy (MRS) over the SMA quantifying glutamate and gamma-aminobutyric acid (GABA) and other metabolites
Prefrontal GABA and Glutamate concentration change as measured with a MEGA-PRESS magnetic resonance spectroscopy sequence following intervention.
Measured: 1 day after completion of open treatment phase
Brief Psychiatric Rating Scale (BPRS)
Total score
Measured: 1 day after completion of open treatment phase
App recorded ratings of auditory verbal hallucinations (AVH)
5 times a day randomized time points for app ratings of AVH
Measured: From first day of open treatment phase, and through one week after completion of treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Dec 2020
- Study start2 Nov 2020
- Primary completion1 Feb 2024
- Study completion8 Feb 2024
Why it stopped: Slow recruitment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Auditory HallucinationStudies of the same condition, open and under way.
- More trials run by Uppsala 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
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- First phase is a cross-over with two randomized blinded sessions with either verum cTBS or sham with wash-out, for each participant, and a second open feasibility treatment phase with 5 sessions/day over four days for participants with distressing auditory verbal hallucinations
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 46 participants (actual)
Sponsor and investigators
- Lead sponsor
- Uppsala University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Robert Boden, MD, Principal investigator, Uppsala University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04651621
- Sponsor's protocol ID
- SMA-AVH
- Acronym
- SMA-AVH
- Status last verified
- Jul 2024
- First submitted
- 6 Nov 2020
- Last updated
- 22 Jul 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Jul 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- SMA Targeted Magnetic Stimulation Against Auditory Verbal Hallucinations
- ClinicalTrials.gov ID
- NCT04651621
- Acronym / sponsor ID
- SMA-AVH / SMA-AVH
- Conditions
- Auditory Hallucination
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Slow recruitment
- Enrolment
- 46 participants (actual)
- Lead sponsor
- Uppsala UniversityUniversity, hospital or other
- Study start
- 2 Nov 2020 (actual)
- Primary completion
- 1 Feb 2024 (actual)
- Study completion
- 8 Feb 2024 (actual)
- First posted
- 3 Dec 2020 (actual)
- 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.
Auditory verbal hallucinations (AVH) are prevalent among patients with psychiatric disorders. Not only being highly stressful and functionally impairing, AVH often persist despite treatment. Recent attempts to treat AVH with add-on repetitive transcranial magnetic stimulation (rTMS) when targeting the temporoparietal junction (TPJ), a language node in the brain, has gained limited success. The aim of this investigation is to reduce AVH with rTMS using continous theta-burst stimulation over a novel target, the supplementary motor area (SMA), in participants with frequent AVH, while also assessing potential neurophysiological mechanisms underlying the symptom.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
- Model description
- First phase is a cross-over with two randomized blinded sessions with either verum cTBS or sham with wash-out, for each participant, and a second open feasibility treatment phase with 5 sessions/day over four days for participants with distressing auditory verbal hallucinations
| Arm | Type | Receives |
|---|---|---|
| Open label active cTBS | Experimental | Device: continuous theta burst stimulation over the SMAFour consecutive days with 40s cTBS, 100% MT over the SMA, five times a day with 50 minutes between stimulations |
| active cTBS | Experimental | Device: continuous theta burst stimulation over the SMAOne test session with 40s active cTBS, 100% MT, over the SMA in the initial double blind cross-over phase |
| Sham cTBS | Sham comparator | Device: sham continuous theta burst stimulation over the SMAOne test session with 40s sham cTBS, 100% MT, over the SMA in the initial double blind cross-over phase with a special sham coil that diverts the magnetic field to be only superficial |
Who may qualify
- Ages
- 18 to 59 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- Reported AVH with a minimum frequency of at least daily occurrence, with onset more than one month ago
- Stable psychopharmacological treatment past month
- Reporting no occurrences of AVH for the past year
- Stable psychopharmacological treatment past month
- No life-time occurrence of AVH
Key exclusion criteria (6 listed)
- Ferromagnetic or electromagnetic implants that may pose a risk during magnetic resonance imaging (MRI) and/or cTBS
- A history of epilepsy
- Pregnancy
- Current substance use disorder or a history of alcohol use disorder as assessed with Alcohol Use Disorders Identification Test (AUDIT), Drug Use Disorders Identification Test (DUDIT), urine samples with test for illicit drugs and Phosphatidylethanol (PEth)
- Daily benzodiazepine use
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 |
|---|---|---|
| continuous theta burst stimulation over the SMAEach cTBS session consists of bursts of three pulses delivered with a rate of 50 Hz, with bursts repeated at a rate of 5 Hz for a total duration of 40 seconds, summing up to 600 pulses, 100% of motor threshold (MT) and applied over bilateral SMA. The target is located in the anterior-posterior direction over the transition between pre-SMA and SMA proper, (cortical point where a vertical line will pass through the anterior commissure). The center of a figure-of-eight coil will be placed over the target, guided with neuronavigation equipment that utilizes the anatomical brain image from the pre-cTBS scanning session. | Device | Open label active cTBS, active cTBS |
| sham continuous theta burst stimulation over the SMAThe same stimulation parameters but a concealed sham coil will be used with only superficial magnetic stimulation to mimic the sensation of the active stimulation | Device | Sham cTBS |
Primary outcome
Amplitude on EEG in speech-listen task
Time frame: 5-30 minutes after intervention
Neurophysiological outcome of the blinded cross-over phase
Change on The Psychotic Symptom Rating Scales (PSYRATS)
Time frame: 1 day after completion of open treatment phase
Auditory Verbal Hallucination symptom interview, total score
6 secondary outcomes
Finger tapping test
Time frame: 5-30 minutes after intervention
Double step saccade-task
Time frame: 20-60 minutes after intervention
Resting state functional magnetic resonance imaging (rsfMRI)
Time frame: 1 day after completion of open treatment phase
Magnetic resonance spectroscopy (MRS) over the SMA quantifying glutamate and gamma-aminobutyric acid (GABA) and other metabolites
Time frame: 1 day after completion of open treatment phase
Brief Psychiatric Rating Scale (BPRS)
Time frame: 1 day after completion of open treatment phase
App recorded ratings of auditory verbal hallucinations (AVH)
Time frame: From first day of open treatment phase, and through one week after completion of treatment
Results and safety
The study was stopped early (reason given: Slow recruitment). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Jul 2024.
- Individual participant dataSharing planned: No
Related trials for Auditory Hallucination
Recruiting
Theta-Burst Transcranial Magnetic Stimulation for Treatment-Resistant Auditory Hallucinations
Auditory Verbal Hallucinations, Schizophrenia
Recruiting
Neuronavigated rTMS for Treatment-Resistant Auditory Hallucinations
Schizophrenia, Auditory Verbal Hallucinations
Recruiting
fMRI-based Neurofeedback to Relieve Drug-resistant Auditory Hallucinations
Schizophrenia, Hallucinations, Auditory
Recruiting
Impact of EDEN College Courses on the Quality of Life of Voice-Hearers
Hallucinations, Auditory
Not yet recruiting
LIFU Effects & Outcomes: Mechanisms Evaluating Striatal Systems Imaging (LEO MESSI)
Schizophrenia, Auditory Hallucinations
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.
Robert Boden, MD principal investigator
Uppsala 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 continuous theta burst stimulation over the SMA in people with Auditory Hallucination, run by Uppsala University at 1 site in Sweden.
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 6 inclusion and 6 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 22 Jul 2024. 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 Sweden. 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?
The study was stopped early (reason given: Slow recruitment). Results are not available in the source record.
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?
Amplitude on EEG in speech-listen task (time frame: 5-30 minutes after intervention). The study lists 2 primary outcomes in all. 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 22 Jul 2024; AzTrials last refreshed its copy on 6 Nov 2026.