Structural and functional brain biomarkers of clinical response to rTMS of medication-resistant auditory hallucinations in schizophrenia patients: study protocol for a randomized sham-controlled double-blind clinical trial.
Adolescent
Adult
Aged
Auditory Perception
Biomarkers
/ blood
Brain
/ diagnostic imaging
Brain Mapping
/ methods
Brain-Derived Neurotrophic Factor
/ blood
Diffusion Magnetic Resonance Imaging
Double-Blind Method
Drug Resistance
Female
France
Hallucinations
Humans
Male
Middle Aged
Randomized Controlled Trials as Topic
Schizophrenia
/ blood
Schizophrenic Psychology
Time Factors
Transcranial Direct Current Stimulation
/ adverse effects
Treatment Outcome
Young Adult
Schizophrenia
auditory verbal hallucinations
clinical response
clinical trial
functional connectivity
non-invasive brain stimulation
predictive biomarkers
repetitive transcranial magnetic stimulation
structural connectivity
Journal
Trials
ISSN: 1745-6215
Titre abrégé: Trials
Pays: England
ID NLM: 101263253
Informations de publication
Date de publication:
23 Apr 2019
23 Apr 2019
Historique:
received:
23
10
2018
accepted:
21
03
2019
entrez:
25
4
2019
pubmed:
25
4
2019
medline:
18
12
2019
Statut:
epublish
Résumé
The potential of non-invasive repetitive transcranial magnetic stimulation (rTMS) to improve auditory verbal hallucinations (AVH) in schizophrenia patients has been increasingly explored over the past decade. Despite highly promising results, high inter-individual variability of clinical response and ineffective outcomes in a significant number of patients underscored the need to identify factors associated with the clinical response to rTMS. It should help improve the efficacy of rTMS in patients with medication-resistant AVH, and allow a better understanding of its neural impact. Here, we describe an exploratory study protocol which aims to identify structural and functional brain biomarkers associated with clinical response after an rTMS treatment for medication-resistant AVH in schizophrenia. Forty-five schizophrenia patients with medication-resistant AVH will be enrolled in a double-blind randomized sham-controlled monocentric clinical trial. Patients will be assigned to a regime of 20 sessions of active or sham 1 Hz rTMS delivered twice a day, 5 days a week for 2 weeks over the left temporo-parietal junction. Response will be assessed after rTMS and patients will be classified in responders or non-responders to treatment. Magnetic resonance imaging (MRI) sessions including diffusion weighted imaging and resting-state functional MRI sequences will be recorded before the onset of the rTMS treatment and 3 days following its discontinuation. The primary outcome measure is difference in fractional anisotropy between responder and non-responder patients at baseline. Differences in resting-state functional MRI data at baseline will be also investigated between responder and non-responder groups. Clinical, neuropsychological, neurophysiological, and blood serum BDNF assessments will be performed at baseline, 3 days, 1 month, and 3 months following rTMS. The aim of this research project is to identify and assess the biomarker value of MRI-based structural and functional biomarkers predicting clinical response to rTMS for AVH in schizophrenia patients. The outcome of the trial should improve patient care by offering them a novel suitable therapy and deepen our understanding on how rTMS may impact AVH and develop more effective therapies adapted to individual patient needs. ClinicalTrials.gov, NCT02755623 . Registered on 22 April 2016.
Sections du résumé
BACKGROUND
BACKGROUND
The potential of non-invasive repetitive transcranial magnetic stimulation (rTMS) to improve auditory verbal hallucinations (AVH) in schizophrenia patients has been increasingly explored over the past decade. Despite highly promising results, high inter-individual variability of clinical response and ineffective outcomes in a significant number of patients underscored the need to identify factors associated with the clinical response to rTMS. It should help improve the efficacy of rTMS in patients with medication-resistant AVH, and allow a better understanding of its neural impact. Here, we describe an exploratory study protocol which aims to identify structural and functional brain biomarkers associated with clinical response after an rTMS treatment for medication-resistant AVH in schizophrenia.
METHODS
METHODS
Forty-five schizophrenia patients with medication-resistant AVH will be enrolled in a double-blind randomized sham-controlled monocentric clinical trial. Patients will be assigned to a regime of 20 sessions of active or sham 1 Hz rTMS delivered twice a day, 5 days a week for 2 weeks over the left temporo-parietal junction. Response will be assessed after rTMS and patients will be classified in responders or non-responders to treatment. Magnetic resonance imaging (MRI) sessions including diffusion weighted imaging and resting-state functional MRI sequences will be recorded before the onset of the rTMS treatment and 3 days following its discontinuation. The primary outcome measure is difference in fractional anisotropy between responder and non-responder patients at baseline. Differences in resting-state functional MRI data at baseline will be also investigated between responder and non-responder groups. Clinical, neuropsychological, neurophysiological, and blood serum BDNF assessments will be performed at baseline, 3 days, 1 month, and 3 months following rTMS.
DISCUSSION
CONCLUSIONS
The aim of this research project is to identify and assess the biomarker value of MRI-based structural and functional biomarkers predicting clinical response to rTMS for AVH in schizophrenia patients. The outcome of the trial should improve patient care by offering them a novel suitable therapy and deepen our understanding on how rTMS may impact AVH and develop more effective therapies adapted to individual patient needs.
TRIAL REGISTRATION
BACKGROUND
ClinicalTrials.gov, NCT02755623 . Registered on 22 April 2016.
Identifiants
pubmed: 31014369
doi: 10.1186/s13063-019-3311-x
pii: 10.1186/s13063-019-3311-x
pmc: PMC6480831
doi:
Substances chimiques
Biomarkers
0
Brain-Derived Neurotrophic Factor
0
BDNF protein, human
7171WSG8A2
Banques de données
ClinicalTrials.gov
['NCT02755623']
Types de publication
Clinical Trial Protocol
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
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