SMA Targeted Magnetic Stimulation Against Auditory Verbal Hallucinations

NCT04651621 | Terminated

• 1 other identifier: SMA-AVH
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 1

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.

Conditions

Auditory Hallucination

Outcome Measures

Primary Outcomes (2)

• Amplitude on EEG in speech-listen task

  Neurophysiological outcome of the blinded cross-over phase

  5-30 minutes after intervention

• Change on The Psychotic Symptom Rating Scales (PSYRATS)

  Auditory Verbal Hallucination symptom interview, total score

  1 day after completion of open treatment phase

Secondary Outcomes (6)

• Finger tapping test

  5-30 minutes after intervention

• Double step saccade-task

  20-60 minutes after intervention

• Resting state functional magnetic resonance imaging (rsfMRI)

  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

  1 day after completion of open treatment phase

• Brief Psychiatric Rating Scale (BPRS)

  1 day after completion of open treatment phase

Study Arms (3)

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

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

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

Device: sham continuous theta burst stimulation over the SMA

Interventions

continuous theta burst stimulation over the SMA DEVICE

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.

Open label active cTBS; active cTBS

sham continuous theta burst stimulation over the SMA DEVICE

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

Sham cTBS

Eligibility Criteria

• Age: 18 Years - 59 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.)

You may not qualify if:

• 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

Sponsors & Collaborators

• Uppsala University: lead

Study Sites (1)

Department of neuroscience, psychiatry, unit for Brain Stimulation and psychiatric clinical trials

Uppsala, 751 85, Sweden

Location

MeSH Terms

Conditions

Hallucinations

Condition Hierarchy (Ancestors)

Perceptual Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Robert Boden, MD

  Uppsala University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Identical sham coil, masked by an independent person.
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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

Study Record Dates

• First Submitted: November 6, 2020
• First Posted: December 3, 2020
• Study Start: November 2, 2020
• Primary Completion: February 1, 2024
• Study Completion: February 8, 2024
• Last Updated: July 22, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share

Locations

SE (1)