SMA-AVH: SMA Targeted Magnetic Stimulation Against Auditory Verbal Hallucinations

Sponsor

Uppsala University (Other)

Overall Status

Recruiting

CT.gov ID

NCT04651621

Collaborator

(none)

Enrollment

Location

Arms

26.9

Anticipated Duration (Months)

2.4

Patients Per Site Per Month

Study Details

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.

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	N/A

Study Design

Study Type:

Interventional

Anticipated 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 hallucinationsFirst 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 :

Nov 2, 2020

Anticipated Primary Completion Date :

Dec 31, 2022

Anticipated Study Completion Date :

Jan 31, 2023

Arms and Interventions

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

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

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

Primary Outcome Measures

Amplitude on EEG in speech-listen task [5-30 minutes after intervention]
Neurophysiological outcome of the blinded cross-over phase
Change on The Psychotic Symptom Rating Scales (PSYRATS) [1 day after completion of open treatment phase]
Auditory Verbal Hallucination symptom interview, total score

Secondary Outcome Measures

Finger tapping test [5-30 minutes after intervention]
Computerized version of the finger tapping test from The Halstead-Reitan Neuropsychological Test Battery, performance
Double step saccade-task [20-60 minutes after intervention]
Performance (Zimmermann et al Sci Rep, 2018).
Resting state functional magnetic resonance imaging (rsfMRI) [1 day after completion of open treatment phase]
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 [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.
Brief Psychiatric Rating Scale (BPRS) [1 day after completion of open treatment phase]
Total score
App recorded ratings of auditory verbal hallucinations (AVH) [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

Criteria

Ages Eligible for Study:

18 Years to 59 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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

Locations

	Site	City	State	Country	Postal Code
1	Department of neuroscience, psychiatry, unit for Brain Stimulation and psychiatric clinical trials	Uppsala		Sweden	751 85

Sponsors and Collaborators

Uppsala University

Investigators

Principal Investigator: Robert Boden, MD, Uppsala University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Uppsala University

ClinicalTrials.gov Identifier:

NCT04651621

Other Study ID Numbers:

SMA-AVH

First Posted:

Dec 3, 2020

Last Update Posted:

May 18, 2022

Last Verified:

May 1, 2022

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Product Manufactured in and Exported from the U.S.:

Additional relevant MeSH terms:

Hallucinations

Study Results

No Results Posted as of May 18, 2022