Research study on brain stimulation for auditory hallucinations in schizophrenia.

Recruiting

Conditions: Schizophrenia,

Registration Number: CTRI/2021/05/033783

Lead Sponsor: Department of Psychiatry National Institute of Mental Health and Neuro Sciences

Brief Summary: **The rationale for the study:**

Schizophrenia is a complex neuropsychiatric disorder characterized by delusions, hallucinations, disorganized behavior, and progressive cognitive deficits. This disorder is ranked among the top ten disabling medical disorders by the World Health Organization. Despite the best of the available treatments, about 25 â€“ 35% of patients with schizophrenia show partial or no clinical improvement and they persist to have symptoms that contribute to a critical component of the disability burden. In addition, most of the existing antipsychotic medications are associated with intolerable side effects as well.

Contextually, alterative paradigms that involve neuromodulatory techniques have been gaining increasing significance in treating schizophrenia patients. Transcranial Direct Current Stimulation [tDCS] has been reported to be useful in treating hallucinations resistant to antipsychotic treatment in schizophrenia patients. Transcranial direct current stimulation (tDCS) is a non-invasive neuromodulatory technique that delivers low intensity, direct current to cortical areas through the surface application of electrodes on the scalp facilitating or inhibiting spontaneous neuronal activity. Continuous theta-burst stimulation is a safe and well-tolerated treatment option in auditory hallucinations when applied unilaterally, as well as, bilaterally. At present, there is no research study that informs whether a schizophrenia patient may differentially respond to one of these two treatments; such information can be very vital in expediting appropriate neuromodulation treatment choice. This research project addresses this compelling research question.

**Aims and hypothesis:**

**Primary**

The primary aim of this study is to identify resting brain functional connectivity markers of response to continuous Theta Burst Stimulation (cTBS) and cathodal transcranial Direct Current Stimulation (c-tDCS) in schizophrenia patients with persistent auditory hallucinations. We hypothesize that a differential pre-treatment resting brain functional connectivity signal will identify responders to cTBS and c-tDCS

**Secondary**

To compare the neurobiological profile of schizophrenia patients with persistent auditory hallucinations with matched healthy controls using multi-modal data (brain imaging, Electroencephalography (EEG), TMS-tDCS perturbation study metrics, Heart Rate Variability (HRV), and neuroplastic gene polymorphisms)

To examine the differential effect of cTBS versus c-tDCS on the neurobiological profile of schizophrenia patients with persistent auditory hallucinations using multi-modal data (brain imaging, EEG, TMS-tDCS perturbation study metrics, HRV) and potential interactions with neuroplasticity gene polymorphisms

To evaluate the predictive utility of multi-modal data (brain imaging, EEG, TMS-tDCS perturbation study metrics, HRV, and neuroplastic gene polymorphisms) in identifying clinical response to cTBS or c-tDCS in schizophrenia patients with persistent auditory hallucinations

**Study Design**

Participants meeting selection criteria will be enrolled in a sequential neuromodulation treatment study. All treatments will be added to ongoing pharmacotherapy. In part-1 (randomized controlled trial), participants will be randomized to receive (a) true cTBS (with sham tDCS) and (b) true c-tDCS (with sham cTBS) to the left TPJ for 15 days. Participants will be blind to the true-sham status of their treatment. An investigator blind to group assignment will assess the change over time in the severity of auditory hallucinations using the Auditory Hallucination Rating Scale (AHRS). Participants with a <30% change in AHRS scores will be considered to be non-responders. In part-2, non-responders to either of the treatments will receive a crossover of the alternative treatment (blinded to the participant and the raters); initiated after a 2-4-week washout period. Treatment response will be reassessed at the end of the cross-over treatment. Study participants will undergo investigations before and after each treatment part to identify biomarkers that predict differential response to these neuromodulatory interventions.

Detailed Description: Not available

Recruitment & Eligibility

Status: Open to Recruitment

Sex: All

Target Recruitment: 210

Inclusion Criteria

1.Schizophrenia Diagnosis (DSM-5); 2.Right-Handedness [Edinburgh Handedness Inventory); 3.Persistence of auditory hallucinations without remission despite treatment with at least one antipsychotic medication at an adequate dose for a minimum period of six weeks.
4.Non-remission defined as a score of moderate or high (>2) on the Global Rating of Hallucinations in the scale for the assessment of positive symptoms.
5.Capacity to consent for research studies as per the assessment using the University of California, San Diego Brief Assessment of Capacity to Consent (UBACC) 6.Written informed consent.

Exclusion Criteria

1.Psychiatric emergency necessitating electroconvulsive therapy; 2.Suicidal risk / any psychiatric emergency; 3.Score of > 6 on Calgary Depression Rating Scale 4.Pregnancy / Post-Partum; 5.Substance use disorder in last six months (except caffeine or nicotine); 6.Co-morbid neurological/medical disease that can affect the brain structure/function; 7.Any Contraindication for Magnetic Resonance Imaging; 8.Any Contraindication for Transcranial Magnetic Stimulation; 9.Any Contraindication for Transcranial Direct Current Stimulation.

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Resting state functional brain connectivity	Time Point-1 (T1): Baseline-1 (i.e before part-1 intervention) \| Time Point-2 (T2): After 15 days of part-1 intervention [true cTBS with sham tDCS (OR) true c-tDCS with sham cTBS] \| Time Point-3 (T3): Baseline-2 (i.e. before part-2 intervention) \| Time Point-4 (T4): After 15 days of part-2 intervention [true cTBS with sham tDCS (OR) true c-tDCS with sham cTBS]

Secondary Outcome Measures

Name	Time	Method
1.Cognitive function as assessed using	Brief Assessment of Cognition in Schizophrenia (BACS)
1.Auditory Hallucination Rating Scale (AHRS)	2.Scale for the Assessment of Positive Symptoms (SAPS)

Trial Locations

Locations (3): Central Institute of Psychiatry
🇮🇳
Ranchi, JHARKHAND, India
Kasturba Medical College
🇮🇳
Udupi, KARNATAKA, India
NIMHANS Hosptial
🇮🇳
Bangalore, KARNATAKA, India
Central Institute of Psychiatry
🇮🇳Ranchi, JHARKHAND, India
Dr Nishant Goyal
Principal investigator
065124551113
psynishant@gmail.com