Efficacy and auditory biomarker analysis of fronto-temporal transcranial direct current stimulation (tDCS) in targeting cognitive impairment associated with recent-onset schizophrenia: study protocol for a multicenter randomized double-blind sham-controlled trial.
Biomarker
Cognitive impairment
Early auditory processing
Noninvasive brain stimulation
Psychiatry
RCT
Schizophrenia
tDCS
Journal
Trials
ISSN: 1745-6215
Titre abrégé: Trials
Pays: England
ID NLM: 101263253
Informations de publication
Date de publication:
24 Feb 2023
24 Feb 2023
Historique:
received:
01
08
2022
accepted:
13
02
2023
entrez:
24
2
2023
pubmed:
25
2
2023
medline:
3
3
2023
Statut:
epublish
Résumé
In parallel to the traditional symptomatology, deficits in cognition (memory, attention, reasoning, social functioning) contribute significantly to disability and suffering in individuals with schizophrenia. Cognitive deficits have been closely linked to alterations in early auditory processes (EAP) that occur in auditory cortical areas. Preliminary evidence indicates that cognitive deficits in schizophrenia can be improved with a reliable and safe non-invasive brain stimulation technique called tDCS (transcranial direct current stimulation). However, a significant proportion of patients derive no cognitive benefits after tDCS treatment. Furthermore, the neurobiological mechanisms of cognitive changes after tDCS have been poorly explored in trials and are thus still unclear. The study is designed as a randomized, double-blind, 2-arm parallel-group, sham-controlled, multicenter trial. Sixty participants with recent-onset schizophrenia and cognitive impairment will be randomly allocated to receive either active (n=30) or sham (n=30) tDCS (20-min, 2-mA, 10 sessions during 5 consecutive weekdays). The anode will be placed over the left dorsolateral prefrontal cortex and the cathode over the left auditory cortex. Cognition, tolerance, symptoms, general outcome and EAP (measured with EEG and multimodal MRI) will be assessed prior to tDCS (baseline), after the 10 sessions, and at 1- and 3-month follow-up. The primary outcome will be the number of responders, defined as participants demonstrating a cognitive improvement ≥Z=0.5 from baseline on the MATRICS Consensus Cognitive Battery total score at 1-month follow-up. Additionally, we will measure how differences in EAP modulate individual cognitive benefits from active tDCS and whether there are changes in EAP measures in responders after active tDCS. Besides proposing a new fronto-temporal tDCS protocol by targeting the auditory cortical areas, we aim to conduct a randomized controlled trial (RCT) with follow-up assessments up to 3 months. In addition, this study will allow identifying and assessing the value of a wide range of neurobiological EAP measures for predicting and explaining cognitive deficit improvement after tDCS. The results of this trial will constitute a step toward the use of tDCS as a therapeutic tool for the treatment of cognitive impairment in recent-onset schizophrenia. ClinicalTrials.gov NCT05440955. Prospectively registered on July 1
Sections du résumé
BACKGROUND
BACKGROUND
In parallel to the traditional symptomatology, deficits in cognition (memory, attention, reasoning, social functioning) contribute significantly to disability and suffering in individuals with schizophrenia. Cognitive deficits have been closely linked to alterations in early auditory processes (EAP) that occur in auditory cortical areas. Preliminary evidence indicates that cognitive deficits in schizophrenia can be improved with a reliable and safe non-invasive brain stimulation technique called tDCS (transcranial direct current stimulation). However, a significant proportion of patients derive no cognitive benefits after tDCS treatment. Furthermore, the neurobiological mechanisms of cognitive changes after tDCS have been poorly explored in trials and are thus still unclear.
METHOD
METHODS
The study is designed as a randomized, double-blind, 2-arm parallel-group, sham-controlled, multicenter trial. Sixty participants with recent-onset schizophrenia and cognitive impairment will be randomly allocated to receive either active (n=30) or sham (n=30) tDCS (20-min, 2-mA, 10 sessions during 5 consecutive weekdays). The anode will be placed over the left dorsolateral prefrontal cortex and the cathode over the left auditory cortex. Cognition, tolerance, symptoms, general outcome and EAP (measured with EEG and multimodal MRI) will be assessed prior to tDCS (baseline), after the 10 sessions, and at 1- and 3-month follow-up. The primary outcome will be the number of responders, defined as participants demonstrating a cognitive improvement ≥Z=0.5 from baseline on the MATRICS Consensus Cognitive Battery total score at 1-month follow-up. Additionally, we will measure how differences in EAP modulate individual cognitive benefits from active tDCS and whether there are changes in EAP measures in responders after active tDCS.
DISCUSSION
CONCLUSIONS
Besides proposing a new fronto-temporal tDCS protocol by targeting the auditory cortical areas, we aim to conduct a randomized controlled trial (RCT) with follow-up assessments up to 3 months. In addition, this study will allow identifying and assessing the value of a wide range of neurobiological EAP measures for predicting and explaining cognitive deficit improvement after tDCS. The results of this trial will constitute a step toward the use of tDCS as a therapeutic tool for the treatment of cognitive impairment in recent-onset schizophrenia.
TRIAL REGISTRATION
BACKGROUND
ClinicalTrials.gov NCT05440955. Prospectively registered on July 1
Identifiants
pubmed: 36829240
doi: 10.1186/s13063-023-07160-z
pii: 10.1186/s13063-023-07160-z
pmc: PMC9951427
doi:
Substances chimiques
Biomarkers
0
Banques de données
ClinicalTrials.gov
['NCT05440955']
Types de publication
Clinical Trial Protocol
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
141Subventions
Organisme : Direction Générale de l'offre de Soins
ID : PHRC IR 2020
Informations de copyright
© 2023. The Author(s).
Références
Encephale. 2022 Aug;48(4):472-473
pubmed: 33994158
Int J Neuropsychopharmacol. 2011 Sep;14(8):1133-45
pubmed: 21320389
Schizophr Bull. 2006 Apr;32(2):366-77
pubmed: 16237200
Transl Psychiatry. 2019 Sep 6;9(1):221
pubmed: 31492832
J Nucl Med. 2018 Nov;59(11):1761-1767
pubmed: 29653974
Schizophr Res. 2018 Jan;191:25-34
pubmed: 28709770
Asian J Psychiatr. 2021 Dec;66:102887
pubmed: 34740126
Trials. 2019 Apr 5;20(1):199
pubmed: 30953544
Nat Rev Neurosci. 2015 Sep;16(9):535-50
pubmed: 26289573
Schizophr Res. 2020 Feb;216:367-373
pubmed: 31822431
Annu Rev Clin Psychol. 2009;5:249-75
pubmed: 19327031
Schizophr Res. 2010 Aug;121(1-3):241-50
pubmed: 20541912
Schizophr Res. 2020 Jun;220:300-310
pubmed: 32204971
Am J Psychiatry. 2008 Feb;165(2):214-20
pubmed: 18172018
Am J Psychiatry. 1995 Oct;152(10):1517-9
pubmed: 7573594
Sci Rep. 2019 Nov 5;9(1):16022
pubmed: 31690846
Schizophr Bull. 2009 Nov;35(6):1059-64
pubmed: 19833806
Encephale. 2000 Jan-Feb;26(1):52-61
pubmed: 10875062
Handb Exp Pharmacol. 2012;(213):11-37
pubmed: 23027411
J Neuropsychiatry Clin Neurosci. 2006 Winter;18(1):54-63
pubmed: 16525071
Trials. 2021 Dec 28;22(1):964
pubmed: 34963486
Mol Psychiatry. 2017 Nov;22(11):1585-1593
pubmed: 28167837
Schizophr Res. 2013 Oct;150(1):51-7
pubmed: 23998953
Schizophr Res. 2017 Mar;181:94-99
pubmed: 27742161
World Psychiatry. 2014 Jun;13(2):153-60
pubmed: 24890068
Am J Psychiatry. 2012 Jul;169(7):719-24
pubmed: 22581236
Lancet. 2022 Jan 29;399(10323):473-486
pubmed: 35093231
Schizophr Bull. 1996;22(1):15-25
pubmed: 8685657
Schizophr Res. 2020 Oct;224:2-10
pubmed: 33129639
JAMA Psychiatry. 2017 Jan 01;74(1):37-46
pubmed: 27926742
Schizophr Res. 2009 Sep;113(2-3):218-25
pubmed: 19464855
JAMA Psychiatry. 2016 Nov 01;73(11):1145-1153
pubmed: 27732692
Am J Psychiatry. 2008 Feb;165(2):203-13
pubmed: 18172019
Schizophr Bull. 2011 Mar;37(2):300-5
pubmed: 20558531
PLoS One. 2020 Jun 4;15(6):e0234121
pubmed: 32497106
Schizophr Bull. 1987;13(2):261-76
pubmed: 3616518
Early Interv Psychiatry. 2021 Jun;15(3):449-456
pubmed: 32452629
Psychol Med. 1988 Nov;18(4):1007-19
pubmed: 3078045
BMC Neurosci. 2018 Apr 19;19(1):25
pubmed: 29673322
Compr Psychiatry. 2003 Jul-Aug;44(4):331-40
pubmed: 12923712
Br J Psychiatry Suppl. 1993 Dec;(22):39-44
pubmed: 8110442
Schizophr Res. 2004 Jun 1;68(2-3):319-29
pubmed: 15099613
J Clin Psychiatry. 2007;68 Suppl 14:8-13
pubmed: 18284272
Schizophr Bull. 2016 May;42(3):571-8
pubmed: 26564898
BMC Psychiatry. 2007 Feb 06;7:7
pubmed: 17284321
Eur Psychiatry. 2019 Jun;59:77-79
pubmed: 31082567
Int J Soc Psychiatry. 2023 Feb;69(1):101-110
pubmed: 34991395
Can J Psychiatry. 2020 Apr;65(4):237-244
pubmed: 31835905
Biol Psychiatry. 2005 Jul 15;58(2):97-104
pubmed: 15936729
Schizophr Bull. 2011 Nov;37(6):1209-17
pubmed: 20410237
Schizophr Res. 2019 Apr;206:135-141
pubmed: 30551982
Can J Psychiatry. 2008 Nov;53(11):783-7
pubmed: 19087473
JAMA Psychiatry. 2020 Feb 1;77(2):121-129
pubmed: 31617873
Psychiatr Serv. 1996 May;47(5):507-11
pubmed: 8740492