Theta Burst Stimulation for Schizophrenia

NCT03288779 | Completed Results DMC FDA Device

• 1 other identifier: Pro00083070
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

Purpose and objective Schizophrenia is a chronic debilitating illness with cognitive deficits that cause serious impairment in psychosocial recovery and with few treatments to remediate these deficits. One area that holds great promise for the development of novel, effective therapies is noninvasive brain stimulation. The investigators have used one form of brain stimulation, transcranial magnetic stimulation (TMS), for some time to modulate and enhance cognitive function in the brain, especially working memory (WM) function, which has a central role in most executive processing that occurs in the brain. Theta burst stimulation (TBS) is a paradigm of TMS which has been shown to effectively modulate WM. Moreover, TBS can modulate gamma neural oscillations in the brain and neural activity, both of which have been implicated in the physiology of WM and pathophysiology of the disease process in schizophrenia, making these measures highly valuable for assessing physiological effects of TBS on cognition, quality of life and cortical inhibition. The purpose of this study is to evaluate the effect of TBS on WM in patients with schizophrenia, to develop evidence for potential brain stimulation techniques to treat cognitive deficits in schizophrenia. Study activities and population group: Study subjects will be inpatient schizophrenic individuals with minimal positive symptoms and predominant cognitive deficits at Duke University Hospital. In an initial session they will be screened and taught a WM task. Following this, one TBS session will follow in which TBS will target dorsolateral prefrontal cortex. They will perform the WM task before, with and after the TBS, with an expected pre-post enhancement of WM performance. Implications - There is a great need for treatments for cognitive deficits in schizophrenia. The results of this study will serve to generate pilot data for a much larger grant to develop a TBS therapy for remediating such cognitive deficits.

Conditions

Schizophrenia; Schizoaffective Disorder

Outcome Measures

Primary Outcomes (1)

• Brief Assessment of Cognition (BACS) Composite T Score

  Performance on tasks included in the Brief Assessment of Cognition in Schizophrenia (BACS) battery, task performed and results recorded on IPAD. The mean change from baseline in total cognitive score on the BACS was calculated as a weighted average of T-scores (normalized for age) from BACS subtests including Verbal Memory, Digit Sequencing, Token Motor, Symbol Coding, Semantic Fluency, Letter Fluency, and Tower of London. The minimum and maximum values possible for this composite T-score of the change from baseline were -131 and 131, respectively. Higher values (positive changes from baseline) indicate better performance.

  30 minutes

Secondary Outcomes (1)

• Change in Gamma and Theta Oscillations as Measured by EEG

  one session, approximately 30 minutes

Study Arms (1)

Theta Burst Stimulation Arm

OTHER

This is a pilot open label study.

Device: Theta Burst Stimulation

Interventions

Theta Burst Stimulation DEVICE

Transcranial magnetic stimulation with theta burst stimulation

Theta Burst Stimulation Arm

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients aged 18-65 years of age with schizophrenia or schizoaffective disorder
• No other mental health diagnoses
• Right handed males and females
• May have mild positive symptoms (score of \</= 21)
• May have negative symptoms
• Ability to provide informed consent
• No restriction on concomitant medications given

You may not qualify if:

• Intellectual disability
• Any organic brain illness Presence of dementia symptoms or traumatic brain injury Primary diagnosis of substance use Seizure disorder Actively symptomatic with PANSS positive symptom sub-scale \>21. Concurrently receiving electroconvulsive therapy (ECT)

Sponsors & Collaborators

• Duke University: lead

Study Sites (1)

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Related Publications (11)

• Green MF, Nuechterlein KH, Gold JM, Barch DM, Cohen J, Essock S, Fenton WS, Frese F, Goldberg TE, Heaton RK, Keefe RS, Kern RS, Kraemer H, Stover E, Weinberger DR, Zalcman S, Marder SR. Approaching a consensus cognitive battery for clinical trials in schizophrenia: the NIMH-MATRICS conference to select cognitive domains and test criteria. Biol Psychiatry. 2004 Sep 1;56(5):301-7. doi: 10.1016/j.biopsych.2004.06.023.

  PMID: 15336511 BACKGROUND

• Keefe RS, Fox KH, Harvey PD, Cucchiaro J, Siu C, Loebel A. Characteristics of the MATRICS Consensus Cognitive Battery in a 29-site antipsychotic schizophrenia clinical trial. Schizophr Res. 2011 Feb;125(2-3):161-8. doi: 10.1016/j.schres.2010.09.015. Epub 2010 Dec 31.

  PMID: 21075600 BACKGROUND

• Young JW, Geyer MA. Developing treatments for cognitive deficits in schizophrenia: the challenge of translation. J Psychopharmacol. 2015 Feb;29(2):178-96. doi: 10.1177/0269881114555252. Epub 2014 Dec 16.

  PMID: 25516372 BACKGROUND

• Barr MS, Farzan F, Arenovich T, Chen R, Fitzgerald PB, Daskalakis ZJ. The effect of repetitive transcranial magnetic stimulation on gamma oscillatory activity in schizophrenia. PLoS One. 2011;6(7):e22627. doi: 10.1371/journal.pone.0022627. Epub 2011 Jul 27.

  PMID: 21818354 BACKGROUND

• Farzan F, Barr MS, Sun Y, Fitzgerald PB, Daskalakis ZJ. Transcranial magnetic stimulation on the modulation of gamma oscillations in schizophrenia. Ann N Y Acad Sci. 2012 Aug;1265:25-35. doi: 10.1111/j.1749-6632.2012.06543.x. Epub 2012 Jul 23.

  PMID: 22823464 BACKGROUND

• Hasan A, Brinkmann C, Strube W, Palm U, Malchow B, Rothwell JC, Falkai P, Wobrock T. Investigations of motor-cortex cortical plasticity following facilitatory and inhibitory transcranial theta-burst stimulation in schizophrenia: a proof-of-concept study. J Psychiatr Res. 2015 Feb;61:196-204. doi: 10.1016/j.jpsychires.2014.12.006. Epub 2014 Dec 19.

  PMID: 25555304 BACKGROUND

• Tikka SK, Nizamie SH, Venkatesh Babu GM, Aggarwal N, Das AK, Goyal N. Safety and Efficacy of Adjunctive Theta Burst Repetitive Transcranial Magnetic Stimulation to Right Inferior Parietal Lobule in Schizophrenia Patients With First-Rank Symptoms: A Pilot, Exploratory Study. J ECT. 2017 Mar;33(1):43-51. doi: 10.1097/YCT.0000000000000343.

  PMID: 27428476 BACKGROUND

• Demirtas-Tatlidede A, Freitas C, Cromer JR, Safar L, Ongur D, Stone WS, Seidman LJ, Schmahmann JD, Pascual-Leone A. Safety and proof of principle study of cerebellar vermal theta burst stimulation in refractory schizophrenia. Schizophr Res. 2010 Dec;124(1-3):91-100. doi: 10.1016/j.schres.2010.08.015.

  PMID: 20817483 BACKGROUND

• Gonzalez-Burgos G, Cho RY, Lewis DA. Alterations in cortical network oscillations and parvalbumin neurons in schizophrenia. Biol Psychiatry. 2015 Jun 15;77(12):1031-40. doi: 10.1016/j.biopsych.2015.03.010. Epub 2015 Mar 17.

  PMID: 25863358 BACKGROUND

• Barr MS, Farzan F, Rusjan PM, Chen R, Fitzgerald PB, Daskalakis ZJ. Potentiation of gamma oscillatory activity through repetitive transcranial magnetic stimulation of the dorsolateral prefrontal cortex. Neuropsychopharmacology. 2009 Oct;34(11):2359-67. doi: 10.1038/npp.2009.79. Epub 2009 Jul 15.

  PMID: 19606086 BACKGROUND

• Keefe RS, Poe M, Walker TM, Harvey PD. The relationship of the Brief Assessment of Cognition in Schizophrenia (BACS) to functional capacity and real-world functional outcome. J Clin Exp Neuropsychol. 2006 Feb;28(2):260-9. doi: 10.1080/13803390500360539.

  PMID: 16484097 BACKGROUND

MeSH Terms

Conditions

Schizophrenia; Psychotic Disorders

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Results Point of Contact

• Title: Steven T Szabo
• Organization: DukeUMC

steven.szabo@duke.edu

3524540101

Study Officials

• Gopalkumar Rakesh, MD

  Duke University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 18, 2017
• First Posted: September 20, 2017
• Study Start: October 24, 2017
• Primary Completion: June 30, 2018
• Study Completion: June 30, 2018
• Last Updated: November 25, 2019
• Results First Posted: November 25, 2019

Record last verified: 2019-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)