Interactions of Fronto-Parietal High Frequency rTMS on Anterior Cingulate Cortex Activation in Schizophrenia

NCT04309370 | Completed Results DMC FDA Device

• 1 other identifier: 1909015657
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 2

Brief Summary

This will be a single site pilot study. 20 subjects with EPP (Early Phase Psychosis), defined as medical record documentation of the onset of clinically significant psychotic symptoms within the past 10 years, will be enrolled. Prior to randomization subjects will undergo fMRI (Functional Magnetic Resonance Imaging) during CC (Cognitive Control) task (Stroop Color-Word paradigm) and resting-state paradigms. This baseline scan will also include a high-resolution structural sequence for neuronavigation purposes. Then, on two separate days, each occurring one-week apart, subjects will receive one session of excitatory (20 Hz) (Hertz) rTMS (Repetitive Transcranial Magnetic Stimulation) targeting the LDLPFC (Left Dorsolateral Prefrontal Cortex) and one session targeting the LSPC (Left Superior Parietal Cortex). The order of stimulation sites will be randomized and counter-balanced. Immediately following each session, subjects will undergo repeat fMRI during CC and RS (Resting State) paradigms. Investigators will also examine the effect of rTMS on CC performance.

Conditions

Schizophrenia

Keywords

schizophrenia; psychosis; early phase psychosis; rTMS

Outcome Measures

Primary Outcomes (2)

• Change in BOLD Signal in Anterior Cingulate Cortex

  Effects of rTMS on anterior cingulate cortex functional activation as measured by blood oxygen level dependent (BOLD) signal change scores during cognitive control Mismatch trials vs. Match trials (i.e., Mismatch - Match). The BOLD signal is measured during a functional magnetic resonance imaging (fMRI) scan and reflects the level of brain activity in the region. Change is calculated as difference between the Mismatch-Match signal at baseline and 30-60 minutes following the intervention. Higher scores indicate a larger increase in brain activity following the intervention.

  1 day

• Change in Cognitive Control Network Functional Connectivity

  The outcome reflects changes in blood oxygen level dependent (BOLD) functional connectivity with anterior cingulate cortex (ACC) and the left dorsolateral prefrontal cortex (LDLPFC) and left superior parietal cortex (LSPC). Functional connectivity is calculated as the Fisher's transformation of the correlation coefficient of the BOLD time series in the ACC with the time series in each target region. Therefore, functional connectivity reflects how similar brain activity is between the target regions (LDLPFC and LSPC) and the ACC, with higher scores indicating greater connectivity. Outcome scores are changes in this connectivity between baseline and 30-60 minutes following the rTMS intervention targeting LDLPFC or LSPC. Positive scores indicate stronger connectivity following rTMS in the cognitive control network.

  1 day

Study Arms (2)

20 Hz rTMS targeting the LDLPFC first, then 20 Hz rTMS targeting the LSPC

EXPERIMENTAL

Device: 20 Hz rTMS

20 Hz rTMS Targeting the LSPC first, then 20 Hz rTMS Targeting the LDLPFC

EXPERIMENTAL

Device: 20 Hz rTMS

Interventions

20 Hz rTMS DEVICE

Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive neuromodulation technique that received FDA clearance for use in treatment resistant major depressive disorder in 2008. rTMS utilizes the application of a repetitively pulsed magnetic field over the scalp to induce an electric field within a discrete area of the cerebral cortex. This electric field results in altered ion flow across the neuronal cellular membrane and ultimately changes in neuronal polarization. rTMS modulates cortical activation depending on the stimulation parameters used. Physiological studies have provided evidence that suggests that high-frequency (HF) rTMS produces an increase in local cortical excitability. Studies have also demonstrated that rTMS may increase or decrease functional connectivity between separate but related cortical structures, utilizing high and low frequency stimulation, respectively.

20 Hz rTMS Targeting the LSPC first, then 20 Hz rTMS Targeting the LDLPFC; 20 Hz rTMS targeting the LDLPFC first, then 20 Hz rTMS targeting the LSPC

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Between 18 and 40 years of age
• Within 10 years of illness onset as defined by entry into treatment for psychotic symptoms
• Able to give informed consent
• Willing and able to adhere to the study schedule
• Mini-International Neuropsychiatric interview (MINI)37-40 diagnosis of schizophrenia
• Clinical stability defined by:
• Subjects must not have experienced an exacerbation of their illness within 4 weeks prior to randomization, leading to an intensification of psychiatric care in the opinion of the investigator. Examples of intensification of care include, but are not limited to: inpatient hospitalization, day/partial hospitalization, outpatient crisis management, or psychiatric treatment in an emergency room AND
• Antipsychotic treatment stability for at least 4 weeks prior to randomization (no change in antipsychotic dosing or addition of new antipsychotic medication)

You may not qualify if:

• Lifetime history of a seizure, excluding febrile seizures and those induced by substance withdrawal
• First degree relative with idiopathic epilepsy or other seizure disorder
• History of significant neurological illness
• History of head trauma as defined by a loss of consciousness or a post-concussive syndrome
• Pregnant or breast feeding
• Known IQ \< 70 based on subject report
• Current acute, serious, or unstable medical conditions
• Metallic objects planted in or near the head, including implanted pacemaker, medication pump, vagal stimulator, deep brain stimulator, TENS unit, ventriculoperitoneal shunt, or cochlear implants
• Contraindications to MRI or otherwise unable to tolerate MRI procedures
• History of electroconvulsive therapy
• Subjects taking clozapine
• Subjects who have participated in a clinical trial with any pharmacological treatment intervention for which they received study-related medication in the 4 weeks prior to randomization
• Subjects considered a high risk for suicidal acts - active suicidal ideation as determined by clinical interview OR any suicide attempt in 90 days prior to screening
• Current DSM-5 diagnosis of alcohol or drug use disorder (excluding nicotine or caffeine)
• Subjects who require concomitant treatment with prohibited medication, as specified in Attachment 2

Sponsors & Collaborators

• Indiana University: lead

Study Sites (2)

IU Center for Neuroimaging

Indianapolis, Indiana, 46202, United States

Location

Prevention and Recovery Center for Early Psychosis

Indianapolis, Indiana, 46202, United States

Location

MeSH Terms

Conditions

Schizophrenia; Psychotic Disorders

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Results Point of Contact

• Title: Clinical Research Manager
• Organization: Indiana University

iupdp@iupui.edu

3178808495

Study Officials

• Tom Hummer, PhD

  Indiana University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Research Professor of Psychiatry

Study Record Dates

• First Submitted: December 20, 2019
• First Posted: March 16, 2020
• Study Start: March 12, 2020
• Primary Completion: April 15, 2022
• Study Completion: April 15, 2022
• Last Updated: August 3, 2023
• Results First Posted: August 3, 2023

Record last verified: 2023-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)