tDCS Combined With rTMS for Negative Symptoms of Schizophrenia

NCT05695144 | Unknown

• 1 other identifier: NIBSNeS
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

Brief Summary

Despite major advances in the field of psychopharmacology in recent years, the majority of treated schizophrenia patients retain disabling symptoms, most commonly a variety of negative symptoms. Currently, clinical treatment of schizophrenia remains dominated by pharmacological control. The current use of antipsychotic medications is effective in controlling the positive symptoms of schizophrenia, but has little effect on the negative symptoms. Neuroimaging and neurophysiological studies have shown that negative symptoms are associated with abnormal brain activity in the combined right and left dorsolateral prefrontal and temporoparietal joint regions, and that physical therapy techniques can modulate cortical activity. Therefore, this study aims to investigate the efficacy of transcranial direct current stimulation(tDCS) combined with repetitive transcranial magnetic stimulation(rTMS) on negative symptoms in patients with schizophrenia and to explore possible mechanisms. The double-blind randomized placebo-controlled study comparing active tDCS stimulation combined with active rTMS stimulation, active rTMS stimulation combined with sham tDCS stimulation, and active tDCS stimulation combined with sham rTMS stimulation to sham tDCS stimulation combined with sham rTMS stimulation at 4 weeks of treatment and 2 weeks of follow-up in patients with predominantly negative symptoms with schizophrenia was studied for efficacy. In addition to the primary observation of changes in the Negative Symptom Assessment Scale (SANS), secondary outcomes include changes in Positive and Negative symptom scale (PANSS) total and negative total scores, changes in the MATRICS Consensus Cognitive Battery (MCCB), changes in local brain activity (functional magnetic resonance imaging, fMRI), white matter integrity (diffusion tensor imaging, DTI), changes in laboratory examination indices changes and changes in psycho-behavioral and EEG index. This is the first clinical trial combining tDCS with rTMS for the treatment of schizophrenia patients with predominantly negative symptoms. This study will provide solid evidence for the combination of tDCS with rTMS for the treatment of negative symptoms in schizophrenia. This study will also help to further explore the mechanisms of tDCS combined with rTMS for the treatment of negative symptoms in schizophrenia in terms of imaging and behavior.

Conditions

Schizophrenia Negative Type

Keywords

rTMS; tDCS; fMRI; ERPs; Cogniton; RCT

Outcome Measures

Primary Outcomes (1)

• Changes in the Scale for Assessment of Negative Symptoms (SANS)

  The primary clinical outcome was the overall severity of negative symptoms of psychosis, as measured by the Scale for Assessment of Negative Symptoms (SANS) at weeks 0(baseline), 2,4 and 6. And the changes between the four assessments were compared in order of time progression。 The Scale for Assessment of Negative Symptoms (SANS) contains 5 subscales, namely: flat or sluggish affect, poor thinking, lack of will, lack of interest or socialization, and attention deficit. The score range is 0-120, and the total score reflects the severity of negative symptoms; the higher the score, the more severe the symptoms.

  weeks 0, 2, 4, and 6

Secondary Outcomes (6)

• Changes in the Positive and Negative symptom scale (PANSS)

  weeks 0, 2, 4, and 6

• Changes in brain imaging markers

  weeks 0 and 4

• Changes in Event-related potentials markers

  weeks 0 and 4

• Changes in psycho-behavioral markers

  weeks 0 and 4

• MATRICS Consensus Cognitive Battery (MCCB)

  weeks 0, 4, and 6

Study Arms (4)

tDCS active stimulation combined with rTMS sham stimulation group

EXPERIMENTAL

1

Device: tDCS active stimulation combined with rTMS sham stimulation

rTMS active stimulation combined with tDCS sham stimulation group

EXPERIMENTAL

2

Device: rTMS active stimulation combined with tDCS sham stimulation

tDCS active stimulation combined with rTMS active stimulation group

EXPERIMENTAL

3

Device: tDCS active stimulation combined with rTMS active stimulation

tDCS sham stimulation combined with rTMS sham stimulation group

EXPERIMENTAL

4

Device: tDCS sham stimulation combined with rTMS sham stimulation

Interventions

tDCS active stimulation combined with rTMS sham stimulation DEVICE

Active tDCS positive stimulation: left dorsolateral prefrontal cortex (DLPFC) or BeamF3 method; negative stimulation: right frontal, 2mA, 20 mins stimulation, 1 time/day, 5 consecutive days, weekend suspension, lasting 4 weeks, total 20 times. Sham stimulation rTMS: Parameters such as stimulation site, current intensity, and stimulation time are kept consistent, keeping the coil facing outward.

tDCS active stimulation combined with rTMS sham stimulation group

rTMS active stimulation combined with tDCS sham stimulation DEVICE

Sham stimulation tDCS: Parameters such as stimulation site, current intensity, and stimulation time are kept consistent, keeping the switch off. Active rTMS: stimulation site: left dorsolateral prefrontal cortex (DLPFC); consisting of a total of 3000 pulses per session at 10Hz (4 seconds on and 16 seconds off) at 110% resting motion threshold (RMT), 40 pulses per string; total 75 strings; 1 time/day, 5 consecutive days, weekend suspension, total 20 times. Resting motor thresholds (RMT) were measured before the start of each day of treatment.

rTMS active stimulation combined with tDCS sham stimulation group

tDCS active stimulation combined with rTMS active stimulation DEVICE

Active tDCS positive stimulation: left dorsolateral prefrontal cortex (DLPFC) or BeamF3 method; negative stimulation: right frontal, 2mA, 20 mins stimulation, 1 time/day, 5 consecutive days, weekend suspension, lasting 4 weeks, total 20 times. Active rTMS: stimulation site: left dorsolateral prefrontal cortex (DLPFC); consisting of a total of 3000 pulses per session at 10Hz (4 seconds on and 16 seconds off) at 110% resting motion threshold (RMT), 40 pulses per string; total 75 strings; 1 time/day, 5 consecutive days, weekend suspension, total 20 times. Resting motor thresholds (RMT) were measured before the start of each day of treatment.

tDCS active stimulation combined with rTMS active stimulation group

tDCS sham stimulation combined with rTMS sham stimulation DEVICE

Sham stimulation tDCS: Parameters such as stimulation site, current intensity, and stimulation time are kept consistent, keeping the switch off. Sham stimulation rTMS: Parameters such as stimulation site, current intensity, and stimulation time are kept consistent, keeping the coil facing outward.

tDCS sham stimulation combined with rTMS sham stimulation group

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Meets Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) diagnostic classification criteria for schizophrenia.
• Age 18-60 years old, gender is not limited.
• Predominantly negative symptoms (PANSS-negative symptom score≥20; or PANSS negative scores are higher than positive scores).
• Stable psychiatric symptoms (negative symptoms, positive symptoms) for more than 4 weeks or more.
• No adjustment in the type or dose of antipsychotics taken in the past 1 months and in the next 1 months
• Patients and Guardians agree to participate in this study and sign an informed consent form.

You may not qualify if:

• Patients with severe physical illness, infectious diseases and immune system diseases, severe neurological diseases, mental retardation or organic brain diseases.
• Pregnant or lactating women.
• Other brain stimulation treatment (ECT, MECT, etc) within past 3 months.
• History of previous seizures.
• Those evaluated as unsuitable for tDCS and rTMS and those who do not cooperate with treatment.
• MRI incompatible implants in the body (such as cochlear implant, insulin pump, pace maker or other metal implants).
• Any risk of having metal particles in the eye, due to manual work without proper eye protections.
• Tattoos containing red pigments.
• Claustrophobia.
• The refusal to be informed of structural brain abnormalities that could be detected during the experiment.

Sponsors & Collaborators

• Tianjin Anding Hospital: lead
• Chinese Academy of Sciences: collaborator

Study Sites (1)

Jie Li

Tianjin, Tianjin Municipality, 300222, China

Location

Related Publications (8)

• Begemann MJ, Brand BA, Curcic-Blake B, Aleman A, Sommer IE. Efficacy of non-invasive brain stimulation on cognitive functioning in brain disorders: a meta-analysis. Psychol Med. 2020 Nov;50(15):2465-2486. doi: 10.1017/S0033291720003670. Epub 2020 Oct 19.

  PMID: 33070785 BACKGROUND

• Gainsford K, Fitzgibbon B, Fitzgerald PB, Hoy KE. Transforming treatments for schizophrenia: Virtual reality, brain stimulation and social cognition. Psychiatry Res. 2020 Jun;288:112974. doi: 10.1016/j.psychres.2020.112974. Epub 2020 Apr 19.

  PMID: 32353694 BACKGROUND

• Kennedy NI, Lee WH, Frangou S. Efficacy of non-invasive brain stimulation on the symptom dimensions of schizophrenia: A meta-analysis of randomized controlled trials. Eur Psychiatry. 2018 Mar;49:69-77. doi: 10.1016/j.eurpsy.2017.12.025. Epub 2018 Feb 3.

  PMID: 29413808 BACKGROUND

• Mitra S, Mehta UM, Binukumar B, Venkatasubramanian G, Thirthalli J. Statistical power estimation in non-invasive brain stimulation studies and its clinical implications: An exploratory study of the meta-analyses. Asian J Psychiatr. 2019 Aug;44:29-34. doi: 10.1016/j.ajp.2019.07.006. Epub 2019 Jul 5.

  PMID: 31302440 BACKGROUND

• Edemann-Callesen H, Winter C, Hadar R. Using cortical non-invasive neuromodulation as a potential preventive treatment in schizophrenia - A review. Brain Stimul. 2021 May-Jun;14(3):643-651. doi: 10.1016/j.brs.2021.03.018. Epub 2021 Apr 2.

  PMID: 33819680 BACKGROUND

• Khanna A, Pascual-Leone A, Michel CM, Farzan F. Microstates in resting-state EEG: current status and future directions. Neurosci Biobehav Rev. 2015 Feb;49:105-13. doi: 10.1016/j.neubiorev.2014.12.010. Epub 2014 Dec 17.

  PMID: 25526823 BACKGROUND

• Sale MV, Mattingley JB, Zalesky A, Cocchi L. Imaging human brain networks to improve the clinical efficacy of non-invasive brain stimulation. Neurosci Biobehav Rev. 2015 Oct;57:187-98. doi: 10.1016/j.neubiorev.2015.09.010. Epub 2015 Sep 26.

  PMID: 26409343 BACKGROUND

• Mally J, Stone TW, Sinko G, Geisz N, Dinya E. Long term follow-up study of non-invasive brain stimulation (NBS) (rTMS and tDCS) in Parkinson's disease (PD). Strong age-dependency in the effect of NBS. Brain Res Bull. 2018 Sep;142:78-87. doi: 10.1016/j.brainresbull.2018.06.014. Epub 2018 Jun 26.

  PMID: 29958911 RESULT

Study Officials

• Shen Li, Doctor

  Tianjin Anding Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief physician；professor

Study Record Dates

• First Submitted: November 15, 2022
• First Posted: January 23, 2023
• Study Start: July 1, 2022
• Primary Completion: September 1, 2024
• Study Completion: December 30, 2024
• Last Updated: January 23, 2023

Record last verified: 2023-01

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)