Augmentation of Working Memory Training With Transcranial Direct Current Stimulation in Patients With Schizophrenia

Schizophrenia Clinical Trial

Official title:

Augmentation of Working Memory Training With Transcranial Direct Current Stimulation (tDCS) in Patients With Schizophrenia

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03621540
• Other study ID #: ESPRIT Training
• Status: Completed
• Phase: N/A
• Start date: April 20, 2018
• Est. completion date: May 30, 2023

Study information

• Verified date: September 2023
• Source: University Hospital Tuebingen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Cognitive impairment is a core symptom of schizophrenia and is in a large part responsible for the poor psychosocial outcome of the disorder. The use of non-invasive brain stimulation techniques as a therapeutic option is just commencing for neuropsychiatric patients. Concerning healthy subjects the investigators have previously shown that anodal tDCS to the right dorsolateral prefrontal cortex (DLPFC) parallel to working memory training can sustainingly enhance performance in a spatial n-back task. Additionally, first translational experiments regarding the use of anodal tDCS to improve working memory (WM) in patients with schizophrenia rendered promising results. On those grounds, the investigators now test the hypothesis that anodal tDCS to the right DLPFC can augment working memory training in patients with schizophrenia.

Description:

Cognitive impairments are a core and debilitating feature of schizophrenia, but effective treatment options are scarce. These deficits develop early in the progression of the disorder, frequently persist throughout lifespan and are considered a possible endophenotype of the disorder. Everyday functioning, work ability and social integration are substantially affected. A proper treatment of cognitive symptoms would probably reduce individual consequences like unemployment or early retirement and alleviate the resulting cost for our societies. Working memory, the ability to temporally maintain and manipulate information, is critically relevant as interface between sensory input and the attainment of behavioral goals. It plays a pivotal role in executive functioning and shares overlapping cognitive processes with social cognition. The characteristic WM deficits in patients with schizophrenia are associated with aberrant dlPFC activation and connectivity, rendering this brain region a prime target for treatment interventions. Cognitive and specifically WM training have been proven effective to change prefrontal activation pattern resulting in improved performance. However, the effect sizes are moderate and the expenditure is high, so that training paradigms are not consistently implemented in regular treatment. A possible way to increase the efficacy of WM training is the augmentation with non-invasive brain stimulation techniques. Transcranial direct current stimulation modulates neuronal membrane potentials and is regulating cortical excitability depending on polarity. Specifically, anodal stimulation can induce long-lasting cortical excitability elevations. First translational studies exploring the effectiveness of tDCS to enhance cognition in patients with schizophrenia yielded promising results.To extend this knowledge, the investigators examine the effect of a tDCS augmented WM training (2 mA to the right dlPFC) in patients with schizophrenia. The WM training consists of two weeks (10 daily sessions) of 20 minute adaptive spatial n-back training, complemented by a Pre/Post session and two follow-up measurements after 4 and 12 weeks. In the two arms parallel study design, patients will be randomized either to the group receiving active anodal tDCS during the training or to the other group receiving sham stimulation during the training. The investigators hypothesize an enhancement of WM performance by anodal tDCS and investigate possible transfer effects in other cognitive tasks, psychopathology, quality of life and subjective cognitive capabilities. The investigators will further analyze the influence of the genetic make-up, neurophysiological signatures and other demographic and cognitive variables on the stimulation effect.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 37
• Est. completion date: May 30, 2023
• Est. primary completion date: December 30, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

Inclusion Criteria:

• diagnosis of schizophrenia or schizoaffective disorder
• age 18-60 years
• Ability to give informed consent
• right handedness
• stable antipsychotic medication one week prior to the experiment and during the training sessions

Exclusion Criteria:

• epilepsy
• metal implants near the head
• pregnancy
• use of antiepileptics
• use of benzodiazepines > 1 mg lorazepam equivalent
• current substance abuse (excluding tabacco)
• missing consent of the legal representative, if existing

Related Conditions & MeSH terms

• Cognition Disorders
• Cognitive Deficits
• Cognitive Dysfunction
• Schizophrenia

Intervention

Device:
• active tDCS
Using the NeuroConn Plus tDCS device, 2 mA anodal tDCS will be applied to the right dorsolateral prefrontal cortex (F4). 15 s fade in and fade out. Total stimulation time of 1365 s. Cathode over contralateral deltoid muscle.
• sham tDCS
Sham mode of the NeuroConn Plus tDCS device with 2 mA stimulation for 45 s at the beginning. Anode over right dorsolateral prefrontal cortex (F4), Cathode over contralateral deltoid muscle. After that, only continuous impedance checking is performed.

Behavioral:
• Adaptive working memory training
Adaptive spatial n-back training.

Locations

Country	Name	City	State
Germany	Department of Psychiatry and Psychotherapy at the Heinrich-Heine-University Duesseldorf	Düsseldorf	North Rhine-Westphalia
Germany	University Hospital Tuebigen, Department of Psychiatry and Psychotherapy	Tuebingen

Sponsors (2)

Lead Sponsor	Collaborator
University Hospital Tuebingen	German Federal Ministry of Education and Research

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Influence of genetic constitution on tDCS effectiveness	Examination of gene polymorphisms (BDNF Val66Met, COMT Val108Met158; CACNA1C) via polymerase chain reaction (PCR).	Pre Training: 3-4 days before training start
Other	Influence of age on tDCS effectiveness	Age in years; demographic questionnaire	Pre Training: 3-4 days before training start
Other	Influence of sex on tDCS effectiveness	Sex: male, female, not specified; self report questionnaire	Pre Training: 3-4 days before training start
Primary	Change (post training - pre training) in working memory task performance (1-,2-,3-back).	Use of d' and response time as dependent variables. Based on signal detection theory, the discriminability index d' (d-prime) is calculated by using the formula d' = Z(hit rate) - Z(false alarm rate).	Pre Training: 3-4 days before training start. Post Training: 3-4 days after completion of working memory training.
Secondary	Change (post training - pre training) in cognitive flexibility and processing speed.	Trail Making Test (TMT) A and B. Results in seconds will be normalized by age and education adjusted standard values. Slower processing time indicates less cognitive flexibility and processing speed.	Pre Training: 3-4 days before training start. Post Training: 3-4 days after completion of training. And changes in follow-up sessions: 4 and 12 weeks after completion of working memory training.
Secondary	Change (follow-up - pre training) in cognitive flexibility and processing speed.	Trail Making Test (TMT) A and B. Results in seconds will be normalized by age and education adjusted standard values. Slower processing time indicates less cognitive flexibility and processing speed.	Pre Training: 3-4 days before training start. Follow-up sessions: 4 and 12 weeks after completion of working memory training.
Secondary	Change (post training - pre training) in cognition.	Measure of different cognitive domains with the Brief Assessment of Cognition in Schizophrenia (BACS). Subscales (Verbal Memory, Working Memory, Motor Function, Verbal Fluency, Speed of Processing, Executive Function) and composite score. Taking age and gender into account, individual test scores are averaged to standardized scores (z-score) . Higher scores indicate better task performance.	Pre Training: 3-4 days before training start. Post Training: 3-4 days after completion of training. And changes in follow-up sessions: 4 and 12 weeks after completion of working memory training.
Secondary	Change (follow-up - pre training) in cognition.	Measure of different cognitive domains with the Brief Assessment of Cognition in Schizophrenia (BACS). Subscales (Verbal Memory, Working Memory, Motor Function, Verbal Fluency, Speed of Processing, Executive Function) and composite score. Taking age and gender into account, individual test scores are averaged to standardized scores (z-score) . Higher scores indicate better task performance.	Pre Training: 3-4 days before training start. Follow-up sessions: 4 and 12 weeks after completion of working memory training.
Secondary	Change (follow-up - pre training) in working memory task performance (1-,2-,3-back).	Use of the d' and response time as dependent variables. Based on signal detection theory, the discriminability index d' (d-prime) is calculated by using the formula d' = Z(hit rate) - Z(false alarm rate).	Pre Training: 3-4 days before training start. Follow up: 4 and 12 weeks after completion of working memory training.
Secondary	Change (post training - pre training) in depressive symptoms.	Calgary Depression Scale for Schizophrenia (CDSS). Maximum score is 27. Higher scores indicate a higher level of depression.	Pre Training: 3-4 days before training start. Post Training: 3-4 days after completion of training.
Secondary	Change (follow-up - pre training) in depressive symptoms.	Calgary Depression Scale for Schizophrenia (CDSS). Maximum score is 27. Higher scores indicate a higher level of depression.	Pre Training: 3-4 days before training start. Follow-up sessions: 4 and 12 weeks after completion of working memory training.
Secondary	Change (post training - pre training) in psychopathology.	Positive and Negative Syndrome Scale (PANSS). The PANSS measures symptom severity on a positive, a negative and a general psychopathology scale. Higher scores indicate more pronounced symptom severity. The PANSS will be analyzed in subscales and as a summed total score.	Pre Training: 3-4 days before training start. Post Training: 3-4 days after completion of training. And changes in follow-up sessions: 4 and 12 weeks after completion of working memory training.
Secondary	Change (follow-up - pre training) in psychopathology.	Positive and Negative Syndrome Scale (PANSS). The PANSS measures symptom severity on a positive, a negative and a general psychopathology scale. Higher scores indicate more pronounced symptom severity. The PANSS will be analyzed in subscales and as a summed total score.	Pre Training: 3-4 days before training start. Follow-up sessions: 4 and 12 weeks after completion of working memory training.
Secondary	Change (post training - pre training) in negative symptoms	Scale for the Assessment of Negative Symptoms (SANS). The total score is calculated by addition of 5 subscales with a maximum score of 25. A higher score indicates more pronounced negative symptoms.	Pre Training: 3-4 days before training start. Post Training: 3-4 days after completion of training.
Secondary	Change (follow-up - pre training) in negative symptoms	Scale for the Assessment of Negative Symptoms (SANS). The total score is calculated by addition of 5 subscales with a maximum score of 25. A higher score indicates more pronounced negative symptoms.	Pre Training: 3-4 days before training start. And changes in follow-up sessions: 4 and 12 weeks after completion of working memory training.
Secondary	Change (post training - pre training) in quality of life.	World Health Organization Quality of Life Questionnaire, short version (WHOQOL-BREF). Four major domains are assessed: physical, psychological, social relationships and environment. It consists of 26 items and a maximum score of 130. Higher scores indicate a higher quality of life.	Pre Training: 3-4 days before training start. Post Training: 3-4 days after completion of training.
Secondary	Change (follow-up - pre training) in quality of life.	World Health Organization Quality of Life Questionnaire, short version (WHOQOL-BREF). Four major domains are assessed: physical, psychological, social relationships and environment. It consists of 26 items and a maximum score of 130. Higher scores indicate a higher quality of life	Pre Training: 3-4 days before training start. Post Training: 3-4 days after completion of training. And changes in follow-up sessions: 4 and 12 weeks after completion of working memory training.
Secondary	Change (post training - pre training) in subjective cognitive capacity.	Subjective Scale to Investigate Cognition in Schizophrenia (SSTICS).Scale with 21 items, maximum score of 84, higher scores indicate more subjective cognitive impairment.	Pre Training: 3-4 days before training start. Post Training: 3-4 days after completion of training.
Secondary	Change (follow-up - pre training) in subjective cognitive capacity.	Subjective Scale to Investigate Cognition in Schizophrenia (SSTICS).Scale with 21 items, maximum score of 84, higher scores indicate more subjective cognitive impairment.	Pre Training: 3-4 days before training start. Follow-up sessions: 4 and 12 weeks after completion of working memory training.
Secondary	Differences in EEG signatures between interventional arms.	resting state connectivity, event-related potentials (ERP), 32-channel EEG	Pre Training: 3-4 days before training start. Post Training: 3-4 days after completion of training