- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT06155695
Auditory Control Enhancement (ACE) in Schizophrenia (ACES)
Targeting the Auditory Control Network With Auditory Control Enhancement (ACE) in Schizophrenia
The purpose of this clinical trial is to investigate neural markers of target engagement to further develop auditory control enhancement (ACE) as a novel, inexpensive, and noninvasive intervention to address treatment-refractory auditory hallucinations. Here, we will address questions about the feasibility and acceptability of ACE, as well as the degree to which ACE results in measurable engagement of biophysical and neurophysiological targets.
Participants will complete:
- Auditory Control Enhancement (ACE): Participants will be assigned by chance (such as a coin flip) into one of two groups to receive a different dosage or level of transcranial direct current stimulation (tDCS) during three sessions of cognitive training. tDCS is used to stimulate the brain for a short period of time. For tDCS one or two thin wet sponges are placed on the head and/or upper arm. The sponges will be connected to electrodes which will deliver a very weak electrical current. The Neuroelectrics Starstim 32 will be used to deliver tDCS.
- Interviews: Before and after ACE, in two separate sessions, participants will be asked questions about a) background; b) functioning in daily life and across different phases of your life and past, present and future medical records.
- Cognitive Tests: During the interview sessions, participants will also perform cognitive tests. Participants will be asked to complete computerized and pen-and-paper tests of attention, concentration, reading, and problem-solving ability.
- EEG scan: Participants will be asked to complete EEG (electroencephalography) studies before and after ACE training. EEG will be measured using the same Neuroelectrics Starstim 32 system used for tDCS. EEG measures the natural activity of the brain using small sensors placed on the scalp. These sensors use conductive gel to provide a connection suitable for recording brain activity. During EEG, participants will watch a silent video while sounds are played over headphones, or sometimes count the sounds. In addition to these auditory tasks, participants will also be asked to perform visual attention tasks, such pressing a button for a letter or image.
- Magnetic Resonance Imaging (MRI) Scan: Participants will also be asked to complete MRI studies before and after ACE training. An MRI is a type of brain scan that takes pictures of the brain that will later be used to create a 3D model of the brain. The MRI does not use radiation, but rather radio waves, a large magnet and a computer to create the images.
Researchers will compare individuals receiving ACE to those receiving sham tDCS during cognitive training to determine effects of ACE.
Study Overview
Status
Conditions
Detailed Description
Study Type
Enrollment (Estimated)
Phase
- Not Applicable
Contacts and Locations
Study Locations
-
-
Pennsylvania
-
Pittsburgh, Pennsylvania, United States, 15213
- Recruiting
- Western Psychiatric Hospital of UPMC
-
Contact:
- Brian Coffman, PhD
- Phone Number: 412-246-5103
- Email: coffmanb@upmc.edu
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Adult
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Between the ages of 18-40
- Schizophrenia, Schizoaffective Disorder, Schizophreniform Disorder, Psychosis not otherwise specified (NOS), Affective Psychosis with mood incongruent hallucinations.
- ability to provide informed consent
- Intelligence quotient (IQ) >= 70, as measured by the Weschler Abbreviated Scale of Intelligence (WASI)
- <5 years since the onset of first psychotic episode
- persistent auditory hallucinations without remission despite attempting >2 antipsychotic medications and having > 1 month of medication compliance
Exclusion Criteria:
- hearing deficit as assessed by audiometry (hearing threshold > 30 decibels (dB) nHL)
- standard MRI contraindications (e.g. cardiac pacemaker, aneurysm clip, cochlear implants, history of metal fragments in body, neurostimulators, weight of 300 lbs. or more, or claustrophobia)
- [self report] head injury with loss of conscious > 10 min, medical illness affecting brain function or structure, significant neurologic disorder (e.g. seizure disorder),
- Diagnostic and Statistical Manual of Mental Disorders (DSM-5) substance use disorder - other than cannabis - and except individuals who have met at least early remission criteria (3 months without dependence symptoms) or a psychotic illness with a temporal relation to a substance use disorder
- currently pregnant or early postpartum (<6 weeks after delivery or miscarriage)
- currently taking medications that affect alertness, other than antipsychotic medication (e.g. sedatives, tranquilizers, muscle relaxants, and sleeping aids)
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Single
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Auditory Control Enhancement (ACE)
tDCS + ACCT
|
ACCT incorporates a subset of components from Cognitive Enhancement Therapy found to have early benefits on the cognitive deficits of interest to the proposed studies and can be conducted more time-efficiently to achieve our specific goals.
ACCT involves approximately 3 hours of computerized neurocognitive training using cognitive control and processing speed training software developed by Ben-Yishay and colleagues.
Deficits in cognitive control are addressed with computer training exercises containing simple stimuli with little inherent emotional or motivational salience.
ACCT requires individuals to be vigilant, inhibit irrelevant stimuli, and shift attention between auditory and visual modalities.
Computer training exercises facilitate reaction time in a temporal mode using auditory cues (The Attention Reaction Conditioner), spatial focusing with visual cues (the Zero Accuracy Conditioner), and temporal vigilance with auditory and visual cues (Time Estimates).
tDCS will be administered using the Starstim system.
We will use the freely available Simulation of Non-Invasive Brain Stimulation (SimNIBS) software to optimally target the rVLPFC and left TPJ in each subject.
Finite element models will be generated using T1 and T2 scans.
We will generate multiple models to maximize on-target stimulation and minimize off-target stimulation, as determined by ratio of the summed current density within and beyond target regions of interest (ROIs).
tDCS current in the active stimulation condition will be maintained at 2.0 milliamps (mA) for the first 45 minutes of each one-hour training session.
Sham stimulation the same current, only the current will be ramped down to 0 mA after 30 seconds.
Our previous research has shown this method to produce indistinguishable skin sensation.
During tDCS, patients will be monitored for possible negative side effects.
|
Sham Comparator: Sham tDCS + ACCT
|
ACCT incorporates a subset of components from Cognitive Enhancement Therapy found to have early benefits on the cognitive deficits of interest to the proposed studies and can be conducted more time-efficiently to achieve our specific goals.
ACCT involves approximately 3 hours of computerized neurocognitive training using cognitive control and processing speed training software developed by Ben-Yishay and colleagues.
Deficits in cognitive control are addressed with computer training exercises containing simple stimuli with little inherent emotional or motivational salience.
ACCT requires individuals to be vigilant, inhibit irrelevant stimuli, and shift attention between auditory and visual modalities.
Computer training exercises facilitate reaction time in a temporal mode using auditory cues (The Attention Reaction Conditioner), spatial focusing with visual cues (the Zero Accuracy Conditioner), and temporal vigilance with auditory and visual cues (Time Estimates).
tDCS will be administered using the Starstim system.
We will use the freely available Simulation of Non-Invasive Brain Stimulation (SimNIBS) software to optimally target the rVLPFC and left TPJ in each subject.
Finite element models will be generated using T1 and T2 scans.
We will generate multiple models to maximize on-target stimulation and minimize off-target stimulation, as determined by ratio of the summed current density within and beyond target regions of interest (ROIs).
tDCS current in the active stimulation condition will be maintained at 2.0 milliamps (mA) for the first 45 minutes of each one-hour training session.
Sham stimulation the same current, only the current will be ramped down to 0 mA after 30 seconds.
Our previous research has shown this method to produce indistinguishable skin sensation.
During tDCS, patients will be monitored for possible negative side effects.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Magnetic field modulation with tDCS current
Time Frame: Week 1
|
We will use General Linear Model (GLM) in SPM12 to assess the parametric modulation of 2nd-echo phase data with the applied tDCS current as a regressor.
Magnetic field modulation of target areas will be quantified as the ratio of mean beta values within target areas in rVLPFC and left TPJ over the mean beta value over cortical voxels beyond these regions of interest.
|
Week 1
|
Change from baseline in oscillatory measure of cognitive control during stimulus evaluation in AX-CPT
Time Frame: Week 3 minus Week 1
|
Mean event-related spectral power will be calculated between 300-500 ms after "A" and "B" stimuli in the gamma band (30-60 Hz), across frontocentral EEG electrodes (Fz, FC1, FCz, FC2).
Cognitive control during stimulus evaluation will be quantified as the mean over "A" and "B" responses.
|
Week 3 minus Week 1
|
Change in Auditory Steady-State Response (ASSR) Modulation with Attention
Time Frame: Week 3 minus Week 1
|
Mean evoked event-related spectral power will be calculated between 100-500 ms after stimulus onset and 35-45 Hz in frontocentral electrodes (Fz, FC1, FCz, FC2).
Attention modulation will be quantified as the difference between signal power measures in attend and ignore conditions (attend minus ignore).
|
Week 3 minus Week 1
|
Change in Auditory Steady-State Response (ASSR) amplitude.
Time Frame: Week 3 minus Week 1
|
Mean evoked event-related spectral power will be calculated between 100-500 ms after stimulus onset and 35-45 Hz in frontocentral electrodes (Fz, FC1, FCz, FC2), from data recorded while participants ignore auditory stimuli.
|
Week 3 minus Week 1
|
Change in cerebral blood flow in auditory control regions
Time Frame: Week 3 minus Week 1
|
Cerebral blood flow (CBF) measured by pseudo-continuous arterial spin labeling (pcASL) will be assessed in right vlPFC and left TPJ target regions
|
Week 3 minus Week 1
|
Retention
Time Frame: Through study completion, an average of 3 weeks
|
Percentage of enrolled participants who did not complete the study
|
Through study completion, an average of 3 weeks
|
Blinding
Time Frame: Week 3
|
Subjective forced-choice impression of treatment condition assessed by a single item on study completion questionnaire - "Which treatment condition do you think you received?
ACE or sham(placebo)?"
|
Week 3
|
Acceptability
Time Frame: Week 3
|
Acceptability rating on a visual analogue scale (0-100; greater = more acceptable) obtained via post-study survey.
|
Week 3
|
Blood-Oxygen Level Dependent (BOLD) response modulation with tDCS current
Time Frame: Week 1
|
We will use General Linear Model (GLM) in Statistical Parametric Modeling (SPM12) to assess the parametric modulation of 2nd-echo magnitude data with the applied tDCS current as a regressor.
BOLD modulation within target areas will be quantified as the ratio of mean beta values within target areas in right ventrolateral prefrontal cortex (rVLPFC) and left temporoparietal junction (TPJ) over the mean beta value over cortical voxels beyond these regions of interest.
|
Week 1
|
Change in oscillatory measure of cognitive control during response preparation in A-X version of the continuous performance test (AX-CPT)
Time Frame: Week 3 minus Week 1
|
Mean event-related spectral power will be calculated between 600-1200 ms after "A" and "B" stimuli in the gamma band (30-60 Hz), across frontocentral EEG electrodes.
Cognitive control during response preparation will be quantified as the difference between "A" and "B" responses (B minus A)).
|
Week 3 minus Week 1
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in MCCB Processing Speed Scale Score
Time Frame: Week 3 minus Week 1
|
t-score (mean = 50, SD = 10; greater=better) obtained on the Processing Speed scale of the MATRICS Consensus Cognitive Battery (MCCB)
|
Week 3 minus Week 1
|
Change in MCCB Attention Scale Score
Time Frame: Week 3 minus Week 1
|
t-score (mean = 50, standard deviation= 10; greater=better) obtained on the Attention scale of the National Institute of Mental Health's Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS)- Consensus Cognitive Battery (MCCB)
|
Week 3 minus Week 1
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in Auditory Hallucination Severity
Time Frame: Week 3 minus Week 1
|
Severity will be assessed using the PSYRATS (Physical scale; range = 0-4; greater = more severe)
|
Week 3 minus Week 1
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Brian A Coffman, PhD, University of Pittsburgh
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- STUDY22070009
- R21MH128823 (U.S. NIH Grant/Contract)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
IPD Sharing Time Frame
IPD Sharing Access Criteria
IPD Sharing Supporting Information Type
- STUDY_PROTOCOL
Drug and device information, study documents
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.
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