Mechanistic Clinical Trial of Individualized tDCS for Hallucinations in Schizophrenia

This project compares standard tDCS to individualized high-definition tDCS (HD-tDCS) for treatment of auditory verbal hallucinations in schizophrenia.

Study Overview

• Status: Withdrawn
• Conditions: Schizophrenia and Related Disorders
• Intervention / Treatment: Device: neuroConn DC-Stimulator MR; Device: Soterix MxN HD-tES

Detailed Description

The large majority of patients with schizophrenia (Sz) experience auditory verbal hallucinations (AVH) as a core feature of their disorder. Treatment-resistant auditory verbal hallucinations (AVH) affect a third of patients with schizophrenia and can cause increased aggression, distress, suicide, and social dysfunction. This project will investigate the efficacy of different types of transcranial direct current stimulation (tDCS), a neurostimulation technique that passes a weak electric current through the brain, in alleviating AVH in Sz patients, and will explore hypotheses regarding brain circuits involved in AVH.

This project compares standard tDCS to individualized high-definition tDCS (HD-tDCS) for treatment of AVH. In standard tDCS, two large electrodes are positioned on the scalp above regions of the brain implicated in abnormal cortical activity associated with auditory verbal hallucinations in Sz. Due to the size of standard tDCS electrodes and the positions required to stimulate language areas, large unrelated areas of the brain are also stimulated. HD-tDCS is a novel technique that uses multiple smaller electrodes to produce a more focal electrical field (EF) than standard tDCS. The HD-tDCS used in this study modulates brain activity in a targeted area without stimulating as many unrelated areas. This targeted inhibition allows us to test hypotheses regarding different cortical regions and their roles in specific features of AVH (e.g. loudness and salience).

Participants are randomized to receive either active standard tDCS or active HD-tDCS targeting one of two language-processing areas of the brain, or a sham version of one of these stimulation types. For each participant receiving HD-tDCS, structural MRI is used to computationally model the electrical field produced in their individual brain anatomy by tDCS. These models are then used to select individualized electrode configurations and current settings to target the same language areas across subjects. The effect of stimulation on relevant brain functions is verified by measuring pre/post treatment changes in resting state functional connectivity (rsFC) within and between targeted language regions, which has been previously linked to AVH symptoms. Differences in behavioral task performance and neurophysiological abnormalities associated with AVH are also tested pre/post treatment.

• Study Type: Interventional
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• DSM-V diagnosis of schizophrenia or schizoaffective disorder
• Capacity and willingness to provide informed consent
• Mean AHRS item score of greater or equal to 2.
• If female and not infertile, must agree to use one of the following forms of contraception for the duration of study participation: systemic hormonal treatment, an IUD which was implanted at least 2 months prior to screening, or "double-barrier" contraception. Women of child bearing potential must have a negative pregnancy test at screening
• Right handed
• Normal hearing
• Taking an antipsychotic medication at a stable dose for at least 4 weeks. All oral and depot antipsychotics are allowable.

Exclusion Criteria:

• Presence or positive history of unstable significant medical or neurological illness
• Substance use disorder (excluding nicotine) within last 90 days, or positive toxicology screen for any substance of abuse
• Pregnancy
• Participation in study of investigational medication/device within 4 weeks
• History of seizure, epilepsy in self or first-degree relatives, stroke, brain surgery, head injury with loss of consciousness >1 hour or clear cognitive sequelae, intracranial metal implants, known structural brain lesion, devices that may be affected by tDCS (pacemaker, medication pump, cochlear implant, implanted brain stimulator)
• Subjects with suicidal ideation with intent or plan (indicated by affirmative answers to items 4 or 5 of the Suicidal Ideation section of the baseline C-SSRS) in the 6 months prior to screening or subjects who represent a significant risk of suicide in the opinion of the investigator
• Frequent and persistent migraines
• Clinically significant skin disease
• Current use of medications known to lower seizure threshold (Lithium, Theophyline, Tricyclic antidepressants, Buproprion >450 mg/day and Clozapine >600 mg/day, brand name and generic methylphenidate/mixed amphetamine salts)
• History of prior clinically significant, adverse response to neurostimulation or open skin wounds that would preclude safe placement of tDCS electrodes
• Contraindication to MRI scanning, including metal implants or claustrophobia. Metal implants, pacemaker, other metal (e.g., shrapnel or surgical prostheses) or paramagnetic objects contained within the body which may present a risk to the subject or interfere with MR scan
• Medicinal patch, unless removed

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: standard tDCS; 20 min of standard 2-electrode transcranial direct current stimulation (2 mA) at a previously reported scalp location.	Device: neuroConn DC-Stimulator MR; standard tDCS, active & sham
Active Comparator: HD-tDCS - anterior target; 20 min of individualized high-density 5-electrode transcranial direct current stimulation to anterior language areas of the brain.	Device: Soterix MxN HD-tES; HD-tDCS, active & sham
Active Comparator: HD-tDCS - posterior target; 20 min of individualized high-density 5-electrode transcranial direct current stimulation to posterior language areas of the brain.	Device: Soterix MxN HD-tES; HD-tDCS, active & sham
Sham Comparator: sham tDCS; sham transcranial direct current stimulation using a brief pulse at the beginning and end of the 20 min intervention.	Device: neuroConn DC-Stimulator MR; standard tDCS, active & sham; Device: Soterix MxN HD-tES; HD-tDCS, active & sham

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Auditory Hallucination Rating Scale (AHRS)	Questionnaire-based assessment instrument for auditory verbal hallucinations, completed by study personnel.	1 week

Collaborators and Investigators

• Sponsor: Columbia University

Study record dates

Study Major Dates

• Study Start (Anticipated): December 1, 2022
• Primary Completion (Anticipated): June 1, 2025
• Study Completion (Anticipated): June 1, 2025

Study Registration Dates

• First Submitted: January 27, 2020
• First Submitted That Met QC Criteria: January 28, 2020
• First Posted (Actual): January 30, 2020

Study Record Updates

• Last Update Posted (Actual): April 5, 2022
• Last Update Submitted That Met QC Criteria: March 24, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Nervous System Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Schizophrenia Spectrum and Other Psychotic Disorders; Perceptual Disorders; Schizophrenia; Hallucinations
• Other Study ID Numbers: 7882

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes