SMA Targeted Magnetic Stimulation Against Auditory Verbal Hallucinations

Not Applicable

Terminated

• Conditions: Auditory Hallucination
• Interventions: Device: continuous theta burst stimulation over the SMA; Device: sham continuous theta burst stimulation over the SMA

• Registration Number: NCT04651621
• Lead Sponsor: Uppsala University

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2020-11-02
• Study First Submitted: 2020-11-06
• Study First Submitted QC: 2020-11-25
• Study First Posted: 2020-12-03
• Primary Completion: 2024-02-01
• Study Completion: 2024-02-08
• Status Verified: 2024-07
• Last Update Submitted: 2024-07-19
• Last Update Posted: 2024-07-22

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 46

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
active cTBS	continuous theta burst stimulation over the SMA	One test session with 40s active cTBS, 100% MT, over the SMA in the initial double blind cross-over phase
Sham cTBS	sham continuous theta burst stimulation over the SMA	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
Open label active cTBS	continuous theta burst stimulation over the SMA	Four consecutive days with 40s cTBS, 100% MT over the SMA, five times a day with 50 minutes between stimulations

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
Double step saccade-task	20-60 minutes after intervention	Performance (Zimmermann et al Sci Rep, 2018).
Finger tapping test	5-30 minutes after intervention	Computerized version of the finger tapping test from The Halstead-Reitan Neuropsychological Test Battery, performance
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

Trial Locations

Locations (1)

Department of neuroscience, psychiatry, unit for Brain Stimulation and psychiatric clinical trials; 🇸🇪 Uppsala, Sweden