| CTRI Number |
CTRI/2017/09/009636 [Registered on: 05/09/2017] Trial Registered Retrospectively |
| Last Modified On: |
06/03/2023 |
| Post Graduate Thesis |
No |
| Type of Trial |
Interventional |
|
Type of Study
|
Other (Specify) [Trancranial Magnetic Stimulation] |
| Study Design |
Randomized, Parallel Group, Placebo Controlled Trial |
|
Public Title of Study
|
Impact of a new kind of delivery of magnetic pulses to the brain called "intermittent Theta Burst Stimulation" for hind part of the human brain "cerebellum" for "negative symptoms in schizophrenia" which are reduced speech, drive for activities and pleasure, emotional expression and socialization |
|
Scientific Title of Study
|
Intermittent Theta Burst Stimulation (iTBS) of Cerebellar Vermis in Schizophrenia: Impact on Negative Symptoms and Brain Connectivity |
| Trial Acronym |
|
|
Secondary IDs if Any
|
| Secondary ID |
Identifier |
| NIL |
NIL |
|
|
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
|
| Name |
Rakshathi Basavaraju |
| Designation |
Research Training Fellow |
| Affiliation |
NATIONAL INSTITUTE OF MENTAL HEALTH AND NEUROSCIENCES |
| Address |
Department of Psychiatry, NIMHANS, Hosur road, Bengaluru- 560029
Department of Psychiatry, NIMHANS, Hosur road, Bengaluru- 560029
Bangalore
KARNATAKA
560029
India |
| Phone |
9900787730 |
| Fax |
|
| Email |
rakshathi.b@gmail.com |
|
Details of Contact Person
Scientific Query
|
| Name |
Rakshathi Basavaraju |
| Designation |
Research Training Fellow |
| Affiliation |
NATIONAL INSTITUTE OF MENTAL HEALTH AND NEUROSCIENCES |
| Address |
Department of Psychiatry, NIMHANS, Hosur road, Bengaluru- 560029
Department of Psychiatry, NIMHANS, Hosur road, Bengaluru- 560029
Bangalore
KARNATAKA
560029
India |
| Phone |
9900787730 |
| Fax |
|
| Email |
rakshathi.b@gmail.com |
|
Details of Contact Person
Public Query
|
| Name |
Rakshathi Basavaraju |
| Designation |
Research Training Fellow |
| Affiliation |
NATIONAL INSTITUTE OF MENTAL HEALTH AND NEUROSCIENCES |
| Address |
Department of Psychiatry, NIMHANS, Hosur road, Bengaluru- 560029
Department of Psychiatry, NIMHANS, Hosur road, Bengaluru- 560029
Bangalore
KARNATAKA
560029
India |
| Phone |
9900787730 |
| Fax |
|
| Email |
rakshathi.b@gmail.com |
|
|
Source of Monetary or Material Support
|
| WELLCOME TRUST-DEPARTMENT OF BIO-TECHNOLOGY INDIA ALLIANCE, H. No. 8-2 684/3/K/19, 1st Floor, Kaushik Society Road No. 12, Banjara Hills, Hyderabad - 500034 |
|
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Primary Sponsor
|
| Name |
Rakshathi Basavraju |
| Address |
Department of Psychiatry, National Institute of Mental Health and Neurosciences, Hosur road, Bengaluru- 560029 |
| Type of Sponsor |
Other [SELF] |
|
|
Details of Secondary Sponsor
|
| Name |
Address |
| Dr Muralidharan K |
Additional Professor, Department of Psychiatry, National Institute of Mental Health and Neurosciences, Hosur road, Bengaluru- 560029 |
|
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Countries of Recruitment
|
India |
|
Sites of Study
|
| No of Sites = 1 |
| Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
| Rakshathi Basavaraju |
Department of Psychiatry, National Institute of Mental Health and Neurosciences |
Hosur road, Bengaluru- 560029
Bangalore
KARNATAKA |
9900787730
rakshathi.b@gmail.com |
|
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Details of Ethics Committee
|
| No of Ethics Committees= 1 |
| Name of Committee |
Approval Status |
| NIMHANS ETHICS COMMITTEE |
Approved |
|
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Regulatory Clearance Status from DCGI
|
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Health Condition / Problems Studied
|
| Health Type |
Condition |
| Patients |
Schizophrenia, |
|
|
Intervention / Comparator Agent
|
| Type |
Name |
Details |
| Intervention |
Intermittent Theta Burst Stimulation |
Two sessions per day spaced four hours apart |
| Comparator Agent |
Sham Transcranial Magnetic Stimulation |
Simulation of Transcranial magnetic stimulation with sham coil with only sound but no magnetic pulses delivered 2 sessions per day spaced four hours apart |
|
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Inclusion Criteria
|
| Age From |
18.00 Year(s) |
| Age To |
50.00 Year(s) |
| Gender |
Both |
| Details |
1. DSM 5 diagnosis of schizophrenia as confirmed by two clinicians independently
2. Medications unchanged at least for the last 3 months and no ECT prescribed in the last 6 months
3. SANS (Scale for Assessment of Negative Symptoms) score of 3 or more on items of global ratings of Affective flattening, Alogia, Avolition-Apathy, Anhedonia-Asociality. |
|
| ExclusionCriteria |
| Details |
1. To avoid confounders likely to affect cognition or treatment response, participants should meet the following criteria
(i) Absence of significant neurological or medical disorders that may produce cognitive impairment (e.g., seizure disorder, traumatic brain injury) as assessed during clinical interview
(ii) Absence of a recent (within the past 3 months) history of substance abuse or dependence (except nicotine)
(iii) Absence of persistent suicidal or homicidal behavior
(iv) Absence of pregnancy, lactation and postpartum state
(vi) Absence of self reported visual or auditory impairment that can impede cognitive assessments.
2. To minimize TMS-related complications, subjects fulfilling any of the risk factors for TMS procedures as assessed using Transcranial Magnetic Stimulation Adult Safety Screen (Keel, Smith, and Wassermann 2001) will be excluded. |
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Method of Generating Random Sequence
|
Computer generated randomization |
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Method of Concealment
|
Sequentially numbered, sealed, opaque envelopes |
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Blinding/Masking
|
Participant, Investigator and Outcome Assessor Blinded |
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Primary Outcome
|
| Outcome |
TimePoints |
| Improvement in negative symptoms and cognitive status compared to baseline |
Baseline, day 6 (5 days after treatment) and 6th week after initiation of treatment |
|
|
Secondary Outcome
|
| Outcome |
TimePoints |
| Increased connectivity within the dorsal attention network (middle frontal gyrus and superior parietal lobule) as examined using resting state functional magnetic resonance imaging. |
Baseline and day 6 (5 days after treatment) |
|
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Target Sample Size
|
Total Sample Size="60"
Sample Size from India="60"
Final Enrollment numbers achieved (Total)= "60"
Final Enrollment numbers achieved (India)="60" |
|
Phase of Trial
|
N/A |
|
Date of First Enrollment (India)
|
01/12/2016 |
| Date of Study Completion (India) |
14/05/2018 |
| Date of First Enrollment (Global) |
Date Missing |
| Date of Study Completion (Global) |
Date Missing |
|
Estimated Duration of Trial
|
Years="1"
Months="8"
Days="0" |
Recruitment Status of Trial (Global)
Modification(s)
|
Not Applicable |
| Recruitment Status of Trial (India) |
Completed |
Publication Details
Modification(s)
|
1. Basavaraju R, Ithal D, Thanki MV, Ramalingaiah AH, Thirthalli J, Reddy RP, Brady RO Jr, Halko MA, Bolo NR, Keshavan MS, Pascual-Leone A, Mehta UM, Kesavan M. Intermittent theta burst stimulation of cerebellar vermis enhances fronto-cerebellar resting state functional connectivity in schizophrenia with predominant negative symptoms: A randomized controlled trial. Schizophr Res. 2021 Dec;238:108-120. doi: 10.1016/j.schres.2021.10.005. Epub 2021 Oct 12. PMID: 34653740; PMCID: PMC8662658.
2.Basavaraju R, Ithal D, Ramalingaiah AH, Thirthalli J, Mehta UM, Kesavan M. "Apathetic to hypomanic/manic": A case series-illustration of emergent mood symptoms during intermittent theta burst stimulation (iTBS) of cerebellar vermis in schizophrenia with predominant negative symptoms. Schizophr Res. 2020 Aug;222:501-502. doi: 10.1016/j.schres.2020.05.037. Epub 2020 Jun 3. PMID: 32505445. |
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Individual Participant Data (IPD) Sharing Statement
|
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
|
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Brief Summary
|
Negative symptoms in schizophrenia are substantially disabling and difficult to treat necessitating novel treatment mechanisms. Theta Burst Stimulation (TBS) is a novel patterned repetitive transcranial magnetic stimulation (rTMS) technique whose safety and efficacy has been established in a small group of schizophrenia patients in an open label study, the target area being cerebellar vermis. The aims of our study is to examine the efficacy of iTBS (intermittent TBS) to the cerebellar vermis for negative symptoms in schizophrenia, to examine the resting state functional connectivity correlates of clinical improvement in negative symptoms and impact on cognitive deficits. The study will be conducted as a double-blind randomized controlled trial, where 60 patients of schizophrenia meeting inclusion and exclusion criteria will be randomized to intervention arm who will receive iTBS and control arm who will receive sham TMS (30 in each group). Assessments that will be carried out at baseline and periodically are positive and negative symptom severity, depressive symptoms, extrapyramidal symptoms, general cognition and social cognitive assessments, vital signs and cerebellar adverse effects. A resting state functional MRI as well as high resolution structural MRI will be obtained at baseline and at the end of the iTBS sessions. Patients will receive iTBS or sham-TMS for 5 days (two-sessions a day, four hours apart). The site of cerebellar stimulation will be guided by MRI guided Neuronavigation. Results will be analysed using mixed-model analysis of variance, correlational and regressional analysis |