Condition or disease | Intervention/treatment | Phase |
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Hallucinations, Verbal Auditory | Device: Transcranial Magnetic Stimulation Drug: Control | Phase 3 |
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.
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 |
Arm | Intervention/treatment |
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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
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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
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Sham Comparator: Control
Control group is received treatment as usual
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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
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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.
Ages Eligible for Study: | 18 Years to 59 Years (Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | Yes |
Inclusion Criteria:
Exclusion Criteria:
Contact: Khamelia Malik, MD | +6181281296600 | khameliapsi@gmail.com | |
Contact: Nurmiati Amir, MD | +6281316111953 | nurmiati.a@gmail.com |
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 |
Principal Investigator: | Khamelia Malik, MD | Department of Psychiatry, RSCM |
Tracking Information | |||||||
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First Submitted Date ICMJE | February 23, 2018 | ||||||
First Posted Date ICMJE | December 4, 2018 | ||||||
Last Update Posted Date | December 4, 2018 | ||||||
Actual Study Start Date ICMJE | February 1, 2018 | ||||||
Estimated Primary Completion Date | December 1, 2018 (Final data collection date for primary outcome measure) | ||||||
Current Primary Outcome Measures ICMJE |
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Original Primary Outcome Measures ICMJE | Same as current | ||||||
Change History | No Changes Posted | ||||||
Current Secondary Outcome Measures ICMJE |
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
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Original Secondary Outcome Measures ICMJE | Same as current | ||||||
Current Other Pre-specified Outcome Measures | Not Provided | ||||||
Original Other Pre-specified Outcome Measures | Not Provided | ||||||
Descriptive Information | |||||||
Brief Title ICMJE | Transcranial Magnetic Stimulation (TMS) for Patients With Treatment Resistant Auditory Verbal Hallucination | ||||||
Official Title ICMJE | TMS for Treatment Resistant Auditory Verbal Hallucination in Schizophrenia | ||||||
Brief Summary | This study will evaluate the effect of repetitive transcranial magnetic stimulation (rTMS) in schizophrenia with treatment resistant auditory verbal hallucination | ||||||
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 ICMJE | Interventional | ||||||
Study Phase ICMJE | Phase 3 | ||||||
Study Design ICMJE | 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
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Condition ICMJE | Hallucinations, Verbal Auditory | ||||||
Intervention ICMJE |
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Study Arms ICMJE |
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Publications * |
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* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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Recruitment Information | |||||||
Recruitment Status ICMJE | Unknown status | ||||||
Estimated Enrollment ICMJE |
40 | ||||||
Original Estimated Enrollment ICMJE | Same as current | ||||||
Estimated Study Completion Date ICMJE | February 1, 2019 | ||||||
Estimated Primary Completion Date | December 1, 2018 (Final data collection date for primary outcome measure) | ||||||
Eligibility Criteria ICMJE |
Inclusion Criteria:
Exclusion Criteria:
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Sex/Gender ICMJE |
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Ages ICMJE | 18 Years to 59 Years (Adult) | ||||||
Accepts Healthy Volunteers ICMJE | Yes | ||||||
Contacts ICMJE | Contact information is only displayed when the study is recruiting subjects | ||||||
Listed Location Countries ICMJE | Indonesia | ||||||
Removed Location Countries | |||||||
Administrative Information | |||||||
NCT Number ICMJE | NCT03762746 | ||||||
Other Study ID Numbers ICMJE | 17-03-0206 | ||||||
Has Data Monitoring Committee | Yes | ||||||
U.S. FDA-regulated Product |
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IPD Sharing Statement ICMJE |
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Responsible Party | Khamelia Malik, Dr Cipto Mangunkusumo General Hospital | ||||||
Study Sponsor ICMJE | Dr Cipto Mangunkusumo General Hospital | ||||||
Collaborators ICMJE | Not Provided | ||||||
Investigators ICMJE |
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PRS Account | Dr Cipto Mangunkusumo General Hospital | ||||||
Verification Date | November 2018 | ||||||
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |