Effect of Neuroplasticity Modulation in tDCS Treatment Response Among Schizophrenia Patients With Auditory Hallucination

NCT04629352 | Recruiting DMC

• 1 other identifier: IA/CPHE/19/1/504591
• Study Type: interventional
• Target: 72
• Locations: 1 country
• Sites: 1

Brief Summary

Schizophrenia is a severe neuropsychiatric disorder of the brain and is also one of the top ten disabling diseases. A common symptom of schizophrenia (SCZ) is hearing voices inside one's heads which others do not. Despite adequate medication, SCZ patients may continue to hear voices that are often rude or unfriendly and cause distress to the patients. Transcranial direct current stimulation (tDCS) is a safe, non-invasive brain stimulation technique that reduces 'hearing voices'. However, how and why add-on tDCS works is unclear. The brain can change itself in response to its environment; this is called neuroplasticity. tDCS possibly changes the brain's environment and/or enhances the brain's ability to respond favourably to its environment. This theory will be examined here by studying changes in brain functions before and after giving tDCS to schizophrenia patients hearing voices. The aim of this study is to examine the brain's neuroplasticity potential as the biological phenomena driving treatment effects of tDCS in Schizophrenia patients with clinically significant and persistent auditory verbal hallucinations. The secondary aims are to answer whether the brain's neuroplasticity potential in schizophrenia patients can predict their responsivity to tDCS treatment for auditory verbal hallucinations, and if chronicity of illness effects tDCS treatment response. The brain's neuroplasticity potential will be examined using neuroimaging and neurophysiological techniques that give information about the integrity of the brain's signal processing efficiency, the chemical concentration of certain bio-molecules within it, and how well different areas of the brain communicate with each other. With this information, the potential role of the brain's neuroplasticity potential in facilitating treatment effects of tDCS can be better understood. With this knowledge, it could be possible personalize tDCS treatment, profile tDCS responders and non-responders based on demographic and biological factors, and prescribe tDCS at the appropriate time within the illness course for maximal benefit to the SCZ patients.

Conditions

Schizophrenia; Schizoaffective Disorder

Keywords

Auditory verbal hallucination; Transcranial Direct Current stimulation (tDCS); Schizophrenia; Neuroplasticity; Psychosis

Outcome Measures

Primary Outcomes (4)

• Neurophysiological Measure: Change in amplitude of N100-related waveforms

  Event-related potential (N100) based indices of changes in early auditory processing and adaptive plasticity in response to tDCS treatment.

  Baseline: Day-1, After single session of tDCS: Day-1, Day-6: After 10 sessions of RCT tDCS

• Neuro-Chemical Measure: Change in concentration of glutamate-glutamine levels

  Spectroscopy based indices of glutamate-glutamine levels at left temporo-parietal junction (TPJ) and left prefrontal cortex (PFC) in response to tDCS treatment.

  Baseline: Day-1, Day-6: After 10 sessions of RCT tDCS

• Neuro-haemodynamic Measure: Change in strength of resting-state-functional-connectivity among brain areas

  Neuroimaging based indices of seed-based resting-state-functional-connectivity (rs-FC) of the left-TPJ with left-PFC in response to tDCS treatment.

  Baseline: Day-1, Day-6: After 10 sessions of RCT tDCS

• Clinical Measure: Change in auditory verbal hallucination score

  Change in auditory hallucination severity as indicated by Auditory Hallucination Rating Scale (AHRS) scores. Minimum score is 2 and maximum score is 41. Higher the score more severe the symptom.

  Baseline: Day-1, Day-6: After 10 sessions of RCT tDCS, One month Follow-up, Three-months follow-up

Secondary Outcomes (2)

• Change in auditory hallucination severity in responsive schizophrenia patients (with ≥25% reduction in auditory hallucination severity at post RCT time point) at 1-month and 3-month follow-up

  One-month Follow-up, Three-month follow-up

• Change in auditory hallucination score in early course and late course schizophrenia patients

  Baseline: Day-1, Day-6: After 10 sessions of RCT tDCS

Other Outcomes (1)

• In a posthoc analysis, a prediction model for the potential of neuroplasticity modulation with tDCS will be attempted using machine learning algorithms and Bayesian approaches.

  Day-6: After 10 sessions of RCT tDCS, One-month follow-up

Study Arms (2)

Verum Accelerated Transcranial Direct Current Stimulation (acctDCS)

EXPERIMENTAL

Each SCZ patient will receive five sessions daily for two days, a 10-session course of tDCS \[anode: left-DLPFC (at F3) and cathode: left-TPJ (midway between C3 and P3); electrode size: 35cm2\]. For the Verum-tDCS condition, 2-mA of constant current will be delivered for 20 minutes, with additional ramp-up and ramp-down of 30 seconds each.

Device: Verum Accelerated Transcranial Direct Current Stimulation (acctDCS)

Sham Accelerated Transcranial Direct Current Stimulation (tDCS)

PLACEBO COMPARATOR

Each SCZ patient will receive five sessions daily for two days, a 10-session course of tDCS \[anode: left-DLPFC (at F3) and cathode: left-TPJ (midway between C3 and P3); electrode size: 35cm2\]. For Sham-tDCS, no current will be delivered beyond the initial ramp-up time.

Device: Sham Accelerated Transcranial Direct Current Stimulation (acctDCS)

Interventions

Verum Accelerated Transcranial Direct Current Stimulation (acctDCS) DEVICE

In verum transcranial direct current stimulation (tDCS), patient will receive five sessions daily for two days, a 10-session course of tDCS \[anode: left-DLPFC (at F3) and cathode: left-TPJ (midway between C3 and P3); electrode size: 35cm2\]. For Verum-tDCS condition, 2-mA of constant current will be delivered for 20-minutes, additional ramp-up and ramp-down of 20 seconds each.

Verum Accelerated Transcranial Direct Current Stimulation (acctDCS)

Sham Accelerated Transcranial Direct Current Stimulation (acctDCS) DEVICE

In sham transcranial direct current stimulation (tDCS), each SCZ patient will receive five sessions daily for two days, a 10-session course of tDCS \[anode: left-DLPFC (at F3) and cathode: left-TPJ (midway between C3 and P3); electrode size: 35cm2\]. However, no current will be delivered beyond initial ramp-up time though the tDCS device display will indicate that 2mA current is being applied.

Sham Accelerated Transcranial Direct Current Stimulation (tDCS)

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Diagnosis of schizophrenia or schizoaffective disorder as per DSM-5 (American Psychiatric Association, 2013)
• Clinically Significant Auditory Verbal Hallucinations
• Right-handedness
• Written informed consent

You may not qualify if:

• Features suggestive of a psychiatric emergency
• Any contraindication to tDCS procedures
• Pregnancy or post-partum status
• Left/Mixed Handedness

Sponsors & Collaborators

• National Institute of Mental Health and Neuro Sciences, India: lead

Study Sites (1)

Department of Psychiatry, National Institute of Mental Health And Neuro Sciences (NIMHANS), Bengaluru, Karnataka

Bengaluru, Karnataka, 560029, India

RECRUITING

MeSH Terms

Conditions

Schizophrenia; Psychotic Disorders; Hallucinations

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders; Perceptual Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Anushree Bose, PhD

  Department of Psychiatry, NIMHANS, Bengaluru, Karnataka, India

  PRINCIPAL INVESTIGATOR

• Ganesan Venkatasubramanian, MD, PhD

  Professor at Department of Psychiatry, NIMHANS, Bengaluru, Karnataka, India

  STUDY CHAIR

Central Study Contacts

Anushree Bose, PhD

CONTACT

+91-8026995366; anushree.cp@gmail.com

Ganesan Venkatasubramanian, MD, PhD

CONTACT

+91-8026995366; gvs@nimhans.ac.in

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: A computer-generated randomization sequence will be used for random assignment of treatment condition. A tDCS device equipped to deliver verum or sham stimulation upon entering manufacturer-assigned codes will be used for the study. Allocation concealment will be maintained by off-site bio-statistician.
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: This prospective longitudinal study will administer add-on accelerated tDCS to SCZ patients in a double-blind, randomised, parallel-arm sham-controlled design. In the accelerated tDCS protocol, 10 sessions (5 sessions per day) will be administered over 2 days. Patients who show ≥20% reduction in AVH severity will be followed up at one month and three months after completion of tDCS-RCT, and other patients will be offered clinician-determined treatment, including open-label accelerated tDCS treatment.

Study Record Dates

• First Submitted: November 2, 2020
• First Posted: November 16, 2020
• Study Start: April 2, 2024
• Primary Completion (Estimated): August 31, 2026
• Study Completion (Estimated): August 31, 2026
• Last Updated: May 22, 2025

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: IPD will be shared 9 months after the publication of the trial results and will stay available for up to 36 months.
• Access Criteria: Researchers seeking to access IPD should write to the investigator(s) with a methodologically sound proposal. The investigator(s) will provide the details of further steps.

Locations

IN (1)