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SMA Targeted Magnetic Stimulation Against Auditory Verbal Hallucinations (SMA-AVH)

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ClinicalTrials.gov Identifier: NCT04651621
Recruitment Status : Recruiting
First Posted : December 3, 2020
Last Update Posted : May 18, 2022
Sponsor:
Information provided by (Responsible Party):
Uppsala University

Study Description
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Brief 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. 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.

Condition or disease Intervention/treatment Phase
Auditory Hallucination Device: continuous theta burst stimulation over the SMA Device: sham continuous theta burst stimulation over the SMA Not Applicable

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 64 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Intervention 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 (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: Identical sham coil, masked by an independent person.
Primary Purpose: Other
Official Title: SMA Targeted Magnetic Stimulation Against Auditory Verbal Hallucinations
Actual Study Start Date : November 2, 2020
Estimated Primary Completion Date : December 31, 2022
Estimated Study Completion Date : January 31, 2023
Arms and Interventions
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Arm Intervention/treatment
Experimental: Open label active cTBS
Four consecutive days with 40s cTBS, 100% MT over the SMA, five times a day with 50 minutes between stimulations
 Device: continuous theta burst stimulation over the SMA
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.
Experimental: active cTBS
One test session with 40s active cTBS, 100% MT, over the SMA in the initial double blind cross-over phase
 Device: continuous theta burst stimulation over the SMA
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 Comparator: Sham cTBS
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
 Device: sham continuous theta burst stimulation over the SMA
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


Outcome Measures
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Primary Outcome Measures :
  1. Amplitude on EEG in speech-listen task [ Time Frame: 5-30 minutes after intervention ]
    Neurophysiological outcome of the blinded cross-over phase

  2. 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


Secondary Outcome Measures :
  1. Finger tapping test [ Time Frame: 5-30 minutes after intervention ]
    Computerized version of the finger tapping test from The Halstead-Reitan Neuropsychological Test Battery, performance

  2. Double step saccade-task [ Time Frame: 20-60 minutes after intervention ]
    Performance (Zimmermann et al Sci Rep, 2018).

  3. Resting state functional magnetic resonance imaging (rsfMRI) [ Time Frame: 1 day after completion of open treatment phase ]
    Resting state SMA connectivity change as measured with fMRI

  4. 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 ]
    Prefrontal GABA and Glutamate concentration change as measured with a MEGA-PRESS magnetic resonance spectroscopy sequence following intervention.

  5. Brief Psychiatric Rating Scale (BPRS) [ Time Frame: 1 day after completion of open treatment phase ]
    Total score

  6. 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 ]
    5 times a day randomized time points for app ratings of AVH


Eligibility Criteria
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Ages Eligible for Study:   18 Years to 59 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

Inclusion criteria for the AVH group:

  • Reported AVH with a minimum frequency of at least daily occurrence, with onset more than one month ago
  • Stable psychopharmacological treatment past month

Inclusion criteria for the non-AVH control group

  • Reporting no occurrences of AVH for the past year
  • Stable psychopharmacological treatment past month

Inclusion criteria for the healthy control group

  • No life-time occurrence of AVH
  • No history of psychiatric disorders as assessed with a Mini-International Neuropsychiatric Interview (M.I.N.I.)

Exclusion Criteria:

  • 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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04651621


Contacts
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Contact: Daniel Larsson +46186112222 daniel.larsson@akademiska.se
Contact: Persson, PhD +46186112222

Locations
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Sweden
Department of neuroscience, psychiatry, unit for Brain Stimulation and psychiatric clinical trials Recruiting
Uppsala, Sweden, 751 85
Contact: Robert Boden, Ph.D, MD    +46 18 611 87 95    robert.boden@neuro.uu.se   
Contact: Jonas Persson, Ph.D    +46 18 611 22 22    jonas.persson@neuro.uu.se   
Sub-Investigator: Martin Cernvall, PhD         
Sub-Investigator: Elin Thörnblom, MD         
Sub-Investigator: Linda Steinholtz, MD         
Principal Investigator: Robert Boden, MD         
Sponsors and Collaborators
Uppsala University
Investigators
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Principal Investigator: Robert Boden, MD Uppsala University
More Information
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Responsible Party: Uppsala University
ClinicalTrials.gov Identifier: NCT04651621    
Other Study ID Numbers: SMA-AVH
First Posted: December 3, 2020    Key Record Dates
Last Update Posted: May 18, 2022
Last Verified: May 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Additional relevant MeSH terms:
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Hallucinations
Perceptual Disorders
Neurobehavioral Manifestations
Neurologic Manifestations
Nervous System Diseases