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

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ClinicalTrials.gov Identifier: NCT03762746
Recruitment Status : Recruiting
First Posted : December 4, 2018
Last Update Posted : December 4, 2018
Sponsor:
Information provided by (Responsible Party):
Khamelia Malik, Dr Cipto Mangunkusumo General Hospital

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

Condition or disease Intervention/treatment Phase
Hallucinations, Verbal Auditory Device: Transcranial Magnetic Stimulation Drug: Control Phase 3

Detailed Description:

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: 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.
Masking: Triple (Participant, Care Provider, Outcomes Assessor)
Masking Description: 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
Primary Purpose: Treatment
Official Title: TMS for Treatment Resistant Auditory Verbal Hallucination in Schizophrenia
Actual Study Start Date : February 1, 2018
Estimated Primary Completion Date : December 1, 2018
Estimated Study Completion Date : February 1, 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Schizophrenia

Arm Intervention/treatment
Active Comparator: 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
Device: 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

Sham Comparator: Control
Control group is received treatment as usual
Drug: 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




Primary Outcome Measures :
  1. Hallucinations change [ Time Frame: 2 weeks ]
    Hallucinations score by Indonesia Version-Psychotic Symptom Rating Scale or PSYRATS. This auditory hallucination scale included 11 items and rated from zero to four. Symptoms over the last week will rated. The dimensions of auditory hallucinations are: frequency, duration, location, loudness, beliefs about origin, negative content, intensity of negative content, amount of distress, intensity of distress, disruption of life and control. Investigators will measure hallucination score before and after 10 session TMS. Total score consist of averaged score of dimensions. A higher score represent a worse outcome.

  2. Source-monitoring ability [ Time Frame: 2 weeks ]

    Source-monitoring score by source monitoring task performance. Participants will ask to distinguish word between 10 silent reading and 10 covert reading and 10 new non-presented word, before TMS and after 10 session TMS. Words are current Indonesian word extract from a verbal fluency task. During the test, word will be presented during 3 seconds on a computer screen.

    To evaluate the source monitoring performance, investigators will consider source attribution, corresponding to number incorrect attribution for source. Score range is between 0-20 A higher total score represents a worse outcome.



Secondary Outcome Measures :
  1. electrophysiological changes [ Time Frame: 2 weeks ]
    This study will investigate all frequency bands (delta, theta, alpha, beta, gamma) coherence in each region of interest of default-mode network. To examine whether functional connectivity between DMN structures differs before and after TMS, the average EEG time series for all nodes in each seed ROI will normalize using transformation and correlations will perform with all other seeds in the DMN network in a 9×9 correlation matrix. The resulting correlation coefficients for each participant will then compare using a two-sided samples t-test to evaluate between-group differences in ROI-ROI connectivity for each seed. A score will represent a functional connectivity between ROIs



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 59 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03762746


Contacts
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Contact: Khamelia Malik, MD +6181281296600 khameliapsi@gmail.com
Contact: Nurmiati Amir, MD +6281316111953 nurmiati.a@gmail.com

Locations
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Indonesia
Department of Psychiatry, Faculty of Medicine, Universitas Indonesia, Cipto Mangunkusumo National Hospital Jakarta Recruiting
Jakarta Pusat, DKI Jakarta, Indonesia
Contact: Kristiana Siste, MD    +6287782516771    ksiste@yahoo.com   
Principal Investigator: Khamelia Malik, MD         
Sub-Investigator: Nurmiati Amir, MD         
Sub-Investigator: Alfonsus Edward, MD         
Sponsors and Collaborators
Dr Cipto Mangunkusumo General Hospital
Investigators
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Principal Investigator: Khamelia Malik, MD Department of Psychiatry, RSCM

Publications:
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Responsible Party: Khamelia Malik, Head Psychiatry Research and Development Unit, Dr Cipto Mangunkusumo General Hospital
ClinicalTrials.gov Identifier: NCT03762746     History of Changes
Other Study ID Numbers: 17-03-0206
First Posted: December 4, 2018    Key Record Dates
Last Update Posted: December 4, 2018
Last Verified: November 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Plan Description: research protocols, analysis

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: Yes
Device Product Not Approved or Cleared by U.S. FDA: No
Product Manufactured in and Exported from the U.S.: Yes

Additional relevant MeSH terms:
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Hallucinations
Perceptual Disorders
Neurobehavioral Manifestations
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms