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

Официальное название

Examining Neuroplasticity Modulation as Mechanistic Basis of tDCS Treatment Effects on Auditory Verbal Hallucination in Schizophrenia

Обзор

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.

Подробное описание

20-30% schizophrenia (SCZ) patients struggle with auditory verbal hallucinations (AVH) minimally responsive to pharmaceutical treatments. An add-on fronto-temporoparietal transcranial direct current stimulation (tDCS) is suggested to address persistent AVH in SCZ patients. High heterogeneity among existing randomized control trials for AVH treatment in SCZ and the lack of empirical studies investigating the tDCS action mechanism warrants a systematic investigation into the mechanistic basis of tDCS action.

This proposal aims to examine the potential for neuroplasticity modulation as the mechanistic factor behind the therapeutic effects of left fronto-temporo-parietal tDCS for treating clinically significant AVH in early-course and chronic SCZ patients. It has been proposed and demonstrated that more tDCS sessions over a shorter interval lead to rapid plasticity induction. Accelerated tDCS protocol delivers a higher number of tDCS sessions over a shorter duration. Accelerated protocol (5 sessions/day for 2 days, inter-session interval\~20 minutes) for the treatment of AVH in SZ showed clinical improvement with concurrent changes in neurophysiological correlates of auditory hallucination pathophysiology. Specifically, this study will examine neuroplasticity potential as a biomarker for tDCS treatment response with an accelerated tDCS (acctDCS) protocol. Using a randomized, double-blind, sham-controlled parallel-arm, pre-post design, changes in neuroplasticity potential with tDCS treatment for AVH in SCZ will be assessed. The four composite primary outcome measures of this study are:

1. changes in N100-derived event-related-potential waveforms (neurophysiological), 2. changes glutamine-glutamate levels (neurochemical), 3. changes in resting-state functional connectivity (neuroimaging), and 4. reduction in AVH severity (clinical).

The secondary objectives of this study are:

1. exploring the correlation between neurobiological measures of neuroplasticity changes induced by tDCS and clinical improvement in AVH to indicate the nature and strength of the relationship between the two; 2. exploring the effect of verum (active) tDCS on early course versus late course SCZ patients will uncover if illness chronicity is a potential barrier to tDCS responsivity; and 3. utilizing disorder-related (age at illness onset, medication, the severity of the symptom, etc.) and biographic (age, sex, years of education, etc.) features of the study sample towards predicting neuroplasticity modulation in the study sample.

Вмешательства

• Устройство Verum Accelerated Transcranial Direct Current Stimulation (acctDCS)
  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.
• Устройство Sham Accelerated Transcranial Direct Current Stimulation (acctDCS)
  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.

Первичные конечные точки

• Neurophysiological Measure: Change in amplitude of N100-related waveforms [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: Baseline: Day-1, Day-6: After 10 sessions of RCT tDCS]
• Clinical Measure: Change in auditory verbal hallucination score [Срок оценки: Baseline: Day-1, Day-6: After 10 sessions of RCT tDCS, One month Follow-up, Three-months follow-up]

Вторичные конечные точки (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 [Срок оценки: One-month Follow-up, Three-month follow-up]
• Change in auditory hallucination score in early course and late course schizophrenia patients [Срок оценки: Baseline: Day-1, Day-6: After 10 sessions of RCT tDCS]

Критерии участия

Критерии включения

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

Критерии исключения

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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Фундаментальное исследование

Центры проведения

Индия · 1 центр

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

Идентификаторы

NCT: NCT04629352 · IA/CPHE/19/1/504591

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗