Non-Invasive Direct Current Stimulation for Cognition in Schizophrenia

Schizophrenia Clinical Trial

Official title:

Non-Invasive Direct Current Stimulation for Cognition in Schizophrenia

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02739347
• Other study ID #: H-42322
• Status: Terminated
• Phase: N/A
• Start date: May 2016
• Est. completion date: June 2019

Study information

• Verified date: June 2022
• Source: Baylor College of Medicine
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study proposes to assess the effect of trans-cranial direct current stimulation (tDCS) on cognitive control, working memory, functional, clinical, and cognitive outcomes in schizophrenia patients.

Description:

Cognitive functions and EEG correlates will be thoroughly assessed in schizophrenia patients undergoing a tDCS treatment and compared with patients receiving a placebo stimulation. The treatment will involve 20 minutes of tDCS application to the left prefrontal and temporo-parietal cortex, twice a day for five days, a procedure shown to be effective in improving other symptoms of psychosis such as negative symptoms and hallucinations. Critically, in addition to standard neuropsychological testing, cognitive assessments will involve tasks that tap cognitive control and working memory, impairments in which comprise two of the core cognitive disturbances in schizophrenia and which have been linked to brain rhythm disturbances measurable by EEG recordings. Investigators will also assess changes in functional outcome by tDCS and investigate relationships between improvements in cognition, brain rhythms and functional outcome. All these assessments will occur just prior to tDCS application, just after completion of the tDCS series, and then again at 2 months follow-up. There will be two separate independent groups of patients who will be randomized to active versus sham treatments. The first group will have early course schizophrenia (less than 5 years of antipsychotic treatment; n=40). The second group will be chronic schizophrenia (greater than 5 years of antipsychotic treatment; n=40).

Relevance

This proposal would be the first integrated study of the effects of tDCS on cognitive symptoms, brain function and functional outcome in schizophrenia. A positive outcome would represent a marked improvement in clinical therapeutics for cognition in psychosis and provide a powerful tool for improving functional outcome in this debilitating disorder. Understanding the impact on brain rhythm disturbances could support the study of similar stimulation-based therapeutic approaches to other neuropsychiatric disorders that shows similar disturbances in cognition and brain rhythms activity, such as bipolar disorder and autism.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 17
• Est. completion date: June 2019
• Est. primary completion date: June 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 50 Years

Eligibility

Inclusion Criteria:

Early course psychosis:

• DSM-V diagnosis of Schizophrenia, Schizoaffective disorder, or schizophreniform disorder.

• ages 18-50 years

• on stable doses of medication for at least one month

• not taking benzodiazepines or mood stabilizers.

• Mild to severe cognitive impairment in MATRICS Consensus Cognitive Battery (composite scores < 40)

Chronic psychosis:

Same as early course psychosis but >5 years of antipsychotic treatment

Exclusion Criteria:

• Diagnostic and Statistical Manual-Version V (DSM-V) diagnosis of mental retardation

• significant head injury

• medical illness affecting brain function or structure

• pregnancy or postpartum (<6 weeks after delivery or miscarriage)

• significant neurologic disorder (e.g seizure disorder)

• inability to provide informed consent

• significant color blindness that affects task performance

• Comorbidity for DSM-V substance abuse disorder within the past one month

• Temporal relation between illness onset and head injury

• Taking benzodiazepines or mood stabilizers (lithium allowed)

• Positive drug screen (excluding THC at baseline)

Related Conditions & MeSH terms

• Psychosis
• Schizophrenia

Intervention

Device:
• Active Trans-cranial direct-current stimulation
Active stimulation group will receive 20 min of 2 mA direct current stimulation.
• Sham Trans-cranial direct current stimulation
This will be an active sham involving brief (15 msec) low current (0.11 mA) pulses every 550 ms.

Locations

Country	Name	City	State
United States	Baylor College of Medicine	Houston	Texas

Sponsors (2)

Lead Sponsor	Collaborator
Baylor College of Medicine	Brain & Behavior Research Foundation

Country where clinical trial is conducted

United States, 

References & Publications (10)

Brunelin J, Mondino M, Gassab L, Haesebaert F, Gaha L, Suaud-Chagny MF, Saoud M, Mechri A, Poulet E. Examining transcranial direct-current stimulation (tDCS) as a treatment for hallucinations in schizophrenia. Am J Psychiatry. 2012 Jul;169(7):719-24. doi: 10.1176/appi.ajp.2012.11071091. Erratum in: Am J Psychiatry. 2012 Dec 1;169(12):1321. — View Citation

Brunoni AR, Nitsche MA, Bolognini N, Bikson M, Wagner T, Merabet L, Edwards DJ, Valero-Cabre A, Rotenberg A, Pascual-Leone A, Ferrucci R, Priori A, Boggio PS, Fregni F. Clinical research with transcranial direct current stimulation (tDCS): challenges and future directions. Brain Stimul. 2012 Jul;5(3):175-195. doi: 10.1016/j.brs.2011.03.002. Epub 2011 Apr 1. Review. — View Citation

Cho RY, Konecky RO, Carter CS. Impairments in frontal cortical gamma synchrony and cognitive control in schizophrenia. Proc Natl Acad Sci U S A. 2006 Dec 26;103(52):19878-83. Epub 2006 Dec 14. — View Citation

Green MF. What are the functional consequences of neurocognitive deficits in schizophrenia? Am J Psychiatry. 1996 Mar;153(3):321-30. Review. — View Citation

Lisman J, Buzsáki G. A neural coding scheme formed by the combined function of gamma and theta oscillations. Schizophr Bull. 2008 Sep;34(5):974-80. doi: 10.1093/schbul/sbn060. Epub 2008 Jun 16. Review. — View Citation

Mondino M, Brunelin J, Palm U, Brunoni AR, Poulet E, Fecteau S. Transcranial Direct Current Stimulation for the Treatment of Refractory Symptoms of Schizophrenia. Current Evidence and Future Directions. Curr Pharm Des. 2015;21(23):3373-83. Review. — View Citation

Stagg CJ, Best JG, Stephenson MC, O'Shea J, Wylezinska M, Kincses ZT, Morris PG, Matthews PM, Johansen-Berg H. Polarity-sensitive modulation of cortical neurotransmitters by transcranial stimulation. J Neurosci. 2009 Apr 22;29(16):5202-6. doi: 10.1523/JNEUROSCI.4432-08.2009. — View Citation

Stagg CJ, Nitsche MA. Physiological basis of transcranial direct current stimulation. Neuroscientist. 2011 Feb;17(1):37-53. doi: 10.1177/1073858410386614. Review. — View Citation

Uhlhaas PJ, Singer W. Abnormal neural oscillations and synchrony in schizophrenia. Nat Rev Neurosci. 2010 Feb;11(2):100-13. doi: 10.1038/nrn2774. Review. — View Citation

Volk DW, Lewis DA. Prefrontal cortical circuits in schizophrenia. Curr Top Behav Neurosci. 2010;4:485-508. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cognitive Control	The investigators will assess cognitive control using the Preparing to Overcome Prepotency (POP) task. The accuracy mean differences between the high and low control conditions will be used as dependent measures.; The study is powered at 0.8 to observe a post-pre treatment improvement in cognitive control with a substantial effect size (d=0.56) compared to sham stimulation with effects relatively stable measured 2 months after baseline. The hypothesized effect size will be d=0.60.	Week 1
Primary	Working Memory	The investigators will assess working memory using a working memory task. The accuracy mean differences between the high and low control conditions will be used as dependent measures.; The study is powered at 0.8 to observe a post-pre treatment improvement in cognitive control with a substantial effect size (d=0.56) compared to sham stimulation with effects relatively stable measured 2 months after baseline. The hypothesized effect size will be d=0.60.	Week 1
Secondary	Negative Symptoms	A secondary outcome measure is the severity of negative symptoms as quantified by Scale for the Assessment of Negative Symptoms (SANS). This study is powered at 0.8 to observe a post-pre treatment improvement in negative symptoms with a moderate effect size (d=0.56) compared to sham stimulation with effects relatively stable measured 2 months after baseline. The hypothesized effect size will be d=0.60.	Week 1
Secondary	Auditory Hallucinations	A secondary outcome measure is the change over time in the severity of auditory hallucinations as assessed by the Auditory Hallucination Rating Scale (AHRS).; In a study conducted using a similar montage and current strength (Brunelin et. al 2012), a reduction in auditory hallucinations with a substantial effect size (d=1.58) was observed in 30 patients with schizophrenia. However, as their study recruited only those patients with severe hallucinations while the current study does not have such an inclusion criterion. The investigators expect a more modest effect size of d=0.60.	Week 1