Back to resultsSMA Targeted Magnetic Stimulation Against Auditory Verbal Hallucinations (SMA-AVH)
Primary Purpose
Auditory Hallucination
Status
Recruiting
Phase
Not Applicable
Locations
Sweden
Study Type
Interventional
Intervention
continuous theta burst stimulation over the SMA
sham continuous theta burst stimulation over the SMA
Sponsored by
About this trial
This is an interventional other trial for Auditory Hallucination
Eligibility 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
Sites / Locations
- Department of neuroscience, psychiatry, unit for Brain Stimulation and psychiatric clinical trialsRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Sham Comparator
Arm Label
Open label active cTBS
active cTBS
Sham cTBS
Arm Description
Four consecutive days with 40s cTBS, 100% MT over the SMA, five times a day with 50 minutes between stimulations
One test session with 40s active cTBS, 100% MT, over the SMA in the initial double blind cross-over phase
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
Outcomes
Primary Outcome Measures
Amplitude on EEG in speech-listen task
Neurophysiological outcome of the blinded cross-over phase
Change on The Psychotic Symptom Rating Scales (PSYRATS)
Auditory Verbal Hallucination symptom interview, total score
Secondary Outcome Measures
Finger tapping test
Computerized version of the finger tapping test from The Halstead-Reitan Neuropsychological Test Battery, performance
Double step saccade-task
Performance (Zimmermann et al Sci Rep, 2018).
Resting state functional magnetic resonance imaging (rsfMRI)
Resting state SMA connectivity change as measured with fMRI
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.
Brief Psychiatric Rating Scale (BPRS)
Total score
App recorded ratings of auditory verbal hallucinations (AVH)
5 times a day randomized time points for app ratings of AVH
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04651621
Brief Title
SMA Targeted Magnetic Stimulation Against Auditory Verbal Hallucinations
Acronym
SMA-AVH
Official Title
SMA Targeted Magnetic Stimulation Against Auditory Verbal Hallucinations
Study Type
Interventional
2. Study Status
Record Verification Date
May 2022
Overall Recruitment Status
Recruiting
Study Start Date
November 2, 2020 (Actual)
Primary Completion Date
December 31, 2022 (Anticipated)
Study Completion Date
January 31, 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Uppsala University
4. Oversight
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
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Auditory Hallucination
7. Study Design
Primary Purpose
Other
Study Phase
Not Applicable
Interventional Study Model
Crossover Assignment
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
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
Identical sham coil, masked by an independent person.
Allocation
Randomized
Enrollment
64 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Open label active cTBS
Arm Type
Experimental
Arm Description
Four consecutive days with 40s cTBS, 100% MT over the SMA, five times a day with 50 minutes between stimulations
Arm Title
active cTBS
Arm Type
Experimental
Arm Description
One test session with 40s active cTBS, 100% MT, over the SMA in the initial double blind cross-over phase
Arm Title
Sham cTBS
Arm Type
Sham Comparator
Arm Description
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
Intervention Type
Device
Intervention Name(s)
continuous theta burst stimulation over the SMA
Intervention Description
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.
Intervention Type
Device
Intervention Name(s)
sham continuous theta burst stimulation over the SMA
Intervention Description
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
Primary Outcome Measure Information:
Title
Amplitude on EEG in speech-listen task
Description
Neurophysiological outcome of the blinded cross-over phase
Time Frame
5-30 minutes after intervention
Title
Change on The Psychotic Symptom Rating Scales (PSYRATS)
Description
Auditory Verbal Hallucination symptom interview, total score
Time Frame
1 day after completion of open treatment phase
Secondary Outcome Measure Information:
Title
Finger tapping test
Description
Computerized version of the finger tapping test from The Halstead-Reitan Neuropsychological Test Battery, performance
Time Frame
5-30 minutes after intervention
Title
Double step saccade-task
Description
Performance (Zimmermann et al Sci Rep, 2018).
Time Frame
20-60 minutes after intervention
Title
Resting state functional magnetic resonance imaging (rsfMRI)
Description
Resting state SMA connectivity change as measured with fMRI
Time Frame
1 day after completion of open treatment phase
Title
Magnetic resonance spectroscopy (MRS) over the SMA quantifying glutamate and gamma-aminobutyric acid (GABA) and other metabolites
Description
Prefrontal GABA and Glutamate concentration change as measured with a MEGA-PRESS magnetic resonance spectroscopy sequence following intervention.
Time Frame
1 day after completion of open treatment phase
Title
Brief Psychiatric Rating Scale (BPRS)
Description
Total score
Time Frame
1 day after completion of open treatment phase
Title
App recorded ratings of auditory verbal hallucinations (AVH)
Description
5 times a day randomized time points for app ratings of AVH
Time Frame
From first day of open treatment phase, and through one week after completion of treatment
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
59 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Daniel Larsson
Phone
+46186112222
Email
daniel.larsson@akademiska.se
First Name & Middle Initial & Last Name or Official Title & Degree
Persson, PhD
Phone
+46186112222
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Robert Boden, MD
Organizational Affiliation
Uppsala University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Department of neuroscience, psychiatry, unit for Brain Stimulation and psychiatric clinical trials
City
Uppsala
ZIP/Postal Code
751 85
Country
Sweden
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Robert Boden, Ph.D, MD
Phone
+46 18 611 87 95
Email
robert.boden@neuro.uu.se
First Name & Middle Initial & Last Name & Degree
Jonas Persson, Ph.D
Phone
+46 18 611 22 22
Email
jonas.persson@neuro.uu.se
First Name & Middle Initial & Last Name & Degree
Martin Cernvall, PhD
First Name & Middle Initial & Last Name & Degree
Elin Thörnblom, MD
First Name & Middle Initial & Last Name & Degree
Linda Steinholtz, MD
First Name & Middle Initial & Last Name & Degree
Robert Boden, MD
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
SMA Targeted Magnetic Stimulation Against Auditory Verbal Hallucinations
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