Transcranial Magnetic Stimulation (TMS) for Patients With Treatment Resistant Auditory Verbal Hallucination

NCT ID: NCT03762746

Last Updated: 2018-12-04

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE3

Total Enrollment

40 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-02-01

Study Completion Date

2019-02-01

Brief Summary

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This study will evaluate the effect of repetitive transcranial magnetic stimulation (rTMS) in schizophrenia with treatment resistant auditory verbal hallucination

Detailed Description

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Brief summary:

This study will evaluate the effect of repetitive transcranial magnetic stimulation (rTMS) in schizophrenia with treatment resistant auditory hallucination

Detailed description:

Auditory verbal hallucinations in schizophrenia disorders have been proposed to be associated with a source- monitoring deficit. The improvement of the monitoring deficit will have major impact on the improvement of hallucinatory symptoms and the social function. Brain network considered to play a major role in source monitoring is the default mode (DM) network. An increasing activity during the brain's resting phase and decreasing activity during stimulus-induced brain activity, increased rest activity in the primary auditory cortex which contributes to conditions, internal speech perceived as a tangible external sound, triggering the occurrence of verbal auditory hallucinations in schizophrenic disorders.

This study will determine if

1-Hz low-frequency, transcranial repetitive magnetic stimulus could be used to inhibit hyperconnectivity between these DM networks and other brain regions, allowing the source-monitoring capability to function properly. This study will measure the oscillatory strength and functional connectivity in the DM network via EEG resting-state activity in schizophrenic with auditory hallucinations before and after rTMS administration. With a seed-based analysis, using the region of interest (ROIs) in the posterior cortex area of the cortex (PPC), precuneus area (PCu), the inferior parietal area (IPC), the medial temporal (MT) area, the medial frontal area (MFC) and the singulatum cortex anterior (ACC) in bilateral hemispheres to create an EEG-based brain activity mapping, measuring cortical spectral power and functional connectivity in the ROIs.

Before starting rTMS, participants will undergo : (1) general and psychiatric assessment, (2) neuropsychological test to evaluate hallucination and source-monitoring ability, (3) an EEG recording (which takes about 1 hour). After these assessment are completed, participants will be randomly assigned (by computer program) to receive either 1 Hz frequency rTMS or placebo stimulation for 20 minutes per day over a 10-day period. During this time, the participants will not know whether they received real or placebo TMS. For 10-days, stimulation will be administered to an area of the left temporal lobe of the brain (temporo-parietal junction).

After trial is completed, participants will be told if they received real or placebo. If the participants have receive only place stimulation, they will then be offered a trial of real rTMS.

TMS is not causing pain, but it can be uncomfortable due to a tingling or knocking sensation, contraction of scalp and facial muscles. There is also a small risk of seizure associated with TMS, but because of the lower frequency of stimulation used in this study (1 stimulation per second), this risk is significant only for participants who have a prior history of seizures, epilepsy, or other neurological problem. Investigators are also concerned that TMS may cause hearing problems. Therefore, investigators will carefully monitor participants for early signs of such problem, using hearing-safety aid to every stimulation session. If investigators suspect that a participant is experiencing problems with hearing, the trial is stopped.

Conditions

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Hallucinations, Verbal Auditory

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Forty schizophrenic or schizoaffective patients with predominant audiotoric hallucinatory symptoms will be given rTMS 1 Hz intervention, 1000-pulse train, 20 min, 90% strength, 1000 pulse in left temporo-parietal cortex for 10 consecutive days (except holidays). Assessment of DN network connectivity in the brain using the results of brain wave decomposition analysis with EEGLAB. For measurement of auditor hall of hallucinations used Indonesian-Psychosis Symptom Rating Scale (INA-PSYRATS) instrument. Source monitoring capability using the INA-Source Monitoring instrument.
Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Caregivers Outcome Assessors
We apply blinding status of trial participants, care providers, and outcome assessors. We are using TMS sham-coil with similarities in appearance, sound, heavy; also we have the timing of final unblinding of all trial participants

Study Groups

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Active

Intervention with transcranial magnetic stimulation (TMS) low frequency 1 Hz , 1000-pulse train, 20 minutes, 90% motor threshold in left temporo-parietal cortex for 10 consecutive days for 20 schizophrenia patients with auditory hallucination

Group Type ACTIVE_COMPARATOR

Transcranial Magnetic Stimulation

Intervention Type DEVICE

A custom TMS stimulator (MagStim) is used to generate repetitive biphasic magnetic pulses. Magnetic pulses are delivered with a figure-8-coil (Magnetic Coil Transducer). During the experiment, rTMS pulse intensity is adjusted to 90% of the motor threshold. Patients will be randomly assigned to receive a 1 Hz. The target area is stimulated for 10 consecutive days. Stimulation at 1 Hz was applied once a day for 10-days

Control

Control group is received treatment as usual

Group Type SHAM_COMPARATOR

Control

Intervention Type DRUG

The control group is receiving treatment as usual. EEG recording and psychopathological ratings are performed one day before the start and on the last day of the study

Interventions

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Transcranial Magnetic Stimulation

A custom TMS stimulator (MagStim) is used to generate repetitive biphasic magnetic pulses. Magnetic pulses are delivered with a figure-8-coil (Magnetic Coil Transducer). During the experiment, rTMS pulse intensity is adjusted to 90% of the motor threshold. Patients will be randomly assigned to receive a 1 Hz. The target area is stimulated for 10 consecutive days. Stimulation at 1 Hz was applied once a day for 10-days

Intervention Type DEVICE

Control

The control group is receiving treatment as usual. EEG recording and psychopathological ratings are performed one day before the start and on the last day of the study

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

1. Met the criteria of all types of schizophrenia or schizoaffective based on structured clinical interview instruments for the DSM-IV axis I disorders (SCID-I)
2. Patients had entered the stabilization phase with 2 to 3 months of antipsychotic treatment and no drug changes within the last 2 (two) months
3. Elementary school graduated (minimum)

Exclusion Criteria

1. Patients with a history of stroke, heart failure, head injury, infection or brain tumor, epilepsy, alcohol and opiate abuse, amphetamines obtained from anamnesis, physical examination and patient medical records
2. Patients with neurological focal deficits such as hemiparesis and cranial nerve paresis
3. Patients with severe cognitive deficits (MMSE scores \<25 in the first and second graders of Senior Secondary School and \<21 in Primary School Graduates)
4. Patients with severe hearing loss were assessed with a 5-word auditory test
5. Patients with mental retardation, assessed using the Wechsler Test of Adult Reading (WTAR) test and data from medical records.
Minimum Eligible Age

18 Years

Maximum Eligible Age

59 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Dr Cipto Mangunkusumo General Hospital

OTHER

Sponsor Role lead

Responsible Party

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Khamelia Malik

Head Psychiatry Research and Development Unit

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Khamelia Malik, MD

Role: PRINCIPAL_INVESTIGATOR

Department of Psychiatry, RSCM

Locations

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Department of Psychiatry, Faculty of Medicine, Universitas Indonesia, Cipto Mangunkusumo National Hospital Jakarta

Jakarta Pusat, DKI Jakarta, Indonesia

Site Status RECRUITING

Countries

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Indonesia

Central Contacts

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Khamelia Malik, MD

Role: CONTACT

+6181281296600

Nurmiati Amir, MD

Role: CONTACT

+6281316111953

Facility Contacts

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Kristiana Siste, MD

Role: primary

+6287782516771

References

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Kubera KM, Barth A, Hirjak D, Thomann PA, Wolf RC. Noninvasive brain stimulation for the treatment of auditory verbal hallucinations in schizophrenia: methods, effects and challenges. Front Syst Neurosci. 2015 Oct 12;9:131. doi: 10.3389/fnsys.2015.00131. eCollection 2015.

Reference Type BACKGROUND
PMID: 26528145 (View on PubMed)

Ray P, Sinha VK, Tikka SK. Adjuvant low-frequency rTMS in treating auditory hallucinations in recent-onset schizophrenia: a randomized controlled study investigating the effect of high-frequency priming stimulation. Ann Gen Psychiatry. 2015 Feb 15;14:8. doi: 10.1186/s12991-015-0046-2. eCollection 2015.

Reference Type BACKGROUND
PMID: 25699086 (View on PubMed)

Moseley P, Fernyhough C, Ellison A. Auditory verbal hallucinations as atypical inner speech monitoring, and the potential of neurostimulation as a treatment option. Neurosci Biobehav Rev. 2013 Dec;37(10 Pt 2):2794-805. doi: 10.1016/j.neubiorev.2013.10.001. Epub 2013 Oct 12.

Reference Type BACKGROUND
PMID: 24125858 (View on PubMed)

Other Identifiers

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17-03-0206

Identifier Type: -

Identifier Source: org_study_id

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