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Mechanistic Clinical Trial of Individualized tDCS for Hallucinations in Schizophrenia

Primary Purpose

Schizophrenia and Related Disorders

Status

Withdrawn

Phase

Not Applicable

Locations

Study Type

Interventional

Intervention

neuroConn DC-Stimulator MR

Soterix MxN HD-tES

About this trial

This is an interventional treatment trial for Schizophrenia and Related Disorders

Eligibility Criteria

18 Years - 55 Years (Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Active Comparator

Sham Comparator

Arm Label

standard tDCS

HD-tDCS - anterior target

HD-tDCS - posterior target

sham tDCS

Arm Description

20 min of standard 2-electrode transcranial direct current stimulation (2 mA) at a previously reported scalp location.

20 min of individualized high-density 5-electrode transcranial direct current stimulation to anterior language areas of the brain.

20 min of individualized high-density 5-electrode transcranial direct current stimulation to posterior language areas of the brain.

sham transcranial direct current stimulation using a brief pulse at the beginning and end of the 20 min intervention.

Outcomes

Primary Outcome Measures

The Auditory Hallucination Rating Scale (AHRS)

Questionnaire-based assessment instrument for auditory verbal hallucinations, completed by study personnel.

Secondary Outcome Measures

Full Information

NCT ID

NCT04248010

First Posted

January 27, 2020

Last Updated

March 24, 2022

Sponsor

Columbia University

1. Study Identification

Unique Protocol Identification Number

NCT04248010

Brief Title

Mechanistic Clinical Trial of Individualized tDCS for Hallucinations in Schizophrenia

Official Title

Mechanistic Clinical Trial of Individualized tDCS for Hallucinations in Schizophrenia

Study Type

Interventional

2. Study Status

Record Verification Date

March 2022

Overall Recruitment Status

Withdrawn

Why Stopped

Modifications in methodology had to be made that make the current registration invalid.

Study Start Date

December 2022 (Anticipated)

Primary Completion Date

June 1, 2025 (Anticipated)

Study Completion Date

June 1, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Columbia University

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Yes

Data Monitoring Committee

5. Study Description

Brief Summary

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

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Schizophrenia and Related Disorders

7. Study Design

Primary Purpose

Treatment

Study Phase

Not Applicable

Interventional Study Model

Parallel Assignment

Model Description

Participants will receive one of the following: standard tDCS, HD-tDCS - anterior target, HD-tDCS - posterior target, or sham.

Masking

ParticipantInvestigatorOutcomes Assessor

Masking Description

Active vs. sham will be masked; type of tDCS (standard or HD) will not be.

Allocation

Randomized

Enrollment

0 (Actual)

8. Arms, Groups, and Interventions

Arm Title

standard tDCS

Arm Type

Active Comparator

Arm Description

20 min of standard 2-electrode transcranial direct current stimulation (2 mA) at a previously reported scalp location.

Arm Title

HD-tDCS - anterior target

Arm Type

Active Comparator

Arm Description

20 min of individualized high-density 5-electrode transcranial direct current stimulation to anterior language areas of the brain.

Arm Title

HD-tDCS - posterior target

Arm Type

Active Comparator

Arm Description

20 min of individualized high-density 5-electrode transcranial direct current stimulation to posterior language areas of the brain.

Arm Title

sham tDCS

Arm Type

Sham Comparator

Arm Description

sham transcranial direct current stimulation using a brief pulse at the beginning and end of the 20 min intervention.

Intervention Type

Device

Intervention Name(s)

neuroConn DC-Stimulator MR

Intervention Description

standard tDCS, active & sham

Intervention Type

Device

Intervention Name(s)

Soterix MxN HD-tES

Intervention Description

HD-tDCS, active & sham

Primary Outcome Measure Information:

Title

The Auditory Hallucination Rating Scale (AHRS)

Description

Questionnaire-based assessment instrument for auditory verbal hallucinations, completed by study personnel.

Time Frame

1 week

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

55 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

12. IPD Sharing Statement

Plan to Share IPD

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Mechanistic Clinical Trial of Individualized tDCS for Hallucinations in Schizophrenia

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