NCT06155695: ACES

Auditory Control Enhancement (ACE) in Schizophrenia

Terminated NA Results posted Last updated 7 April 2026

What this trial tests

NA trial testing Transcranial Direct Current Stimulation (tDCS) in Auditory Hallucinations in 12 participants. Terminated before completion.

Timeline

5 September 2023

Primary endpoint
18 December 2024

18 December 2024

Quick facts

Lead sponsor	Brian A Coffman, PhD
Phase	NA
Status	Terminated
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	single
Primary purpose	treatment
Enrollment	12
Start date	5 September 2023
Primary completion	18 December 2024
Estimated completion	18 December 2024
Sites	1 location across United States

Drugs / interventions tested

• Transcranial Direct Current Stimulation (tDCS)
• Auditory Cognitive Control Training (ACCT)

Conditions studied

• Auditory Hallucinations — all drugs for Auditory Hallucinations →

Sponsor

Brian A Coffman, PhD

Who can join

Adults 18 to 40, any sex, with Auditory Hallucinations. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Change From Baseline in Oscillatory Measure of Cognitive Control During Stimulus Evaluation in AX Version of the Continuous Performance Test (AX-CPT) Primary · Week 3 minus Week 1

Most trials in this task show letter A, then X, requiring response. Occasionally, stimuli other than A (generally called "B" stimuli) or other than X (generally, "Y" stimuli) are presented, requiring no response. Mean event-related spectral magnitude calculated between 200-500 ms after "A" and "B" stimuli in the beta band (15-25 Hz), across frontocentral EEG electrodes (Fz, FC1, FCz, FC2, Cz). Signals were averaged over electrodes, time, and frequency. Values reported here represent the mean of "A" and "B" responses.

Group	Value	95% CI
Auditory Control Enhancement (ACE)	-0.0394	± 0.0464
Sham tDCS + ACCT	0.0024	± 0.038

Change From Baseline in Oscillatory Measure of Cognitive Control During Response Preparation in A-X Version of the Continuous Performance Test (AX-CPT) Primary · Week 3 minus Week 1

Most trials in this task show letter A, then X, requiring response. Occasionally, stimuli other than A (generally called "B" stimuli) or other than X (generally, "Y" stimuli) are presented, requiring no response. Mean event-related spectral magnitude calculated between 600-1200 ms after "A" and "B" stimuli in the gamma band (30-60 Hz), across frontocentral EEG electrodes (Fz, FC1, FCz, FC2, Cz). Signals were averaged over electrodes, time, and frequency. Values reported here represent the difference between "A" and "B" responses (B minus A)).

Group	Value	95% CI
Auditory Control Enhancement (ACE)	-0.0504	± 0.0708
Sham tDCS + ACCT	-0.0075	± 0.0484

Change in Auditory Steady-State Response (ASSR) Modulation With Attention Primary · Week 3 minus Week 1

Mean evoked event-related spectral magnitude calculated between 100-500 ms after stimulus onset and 35-45 Hz in frontocentral electrodes (Fz, FC1, FCz, FC2, Cz). Magnitude is calculated as the average over electrodes, time, and frequency. These values represent the difference between signal magnitude measures in attend and ignore conditions (attend minus ignore).

Group	Value	95% CI
Auditory Control Enhancement (ACE)	0.339	± 0.328
Sham tDCS + ACCT	-0.071	± 0.113

Change in Auditory Steady-State Response (ASSR) Amplitude. Primary · Week 3 minus Week 1

Mean evoked event-related spectral magnitude calculated between 100-500 ms after stimulus onset and 35-45 Hz in frontocentral electrodes (Fz, FC1, FCz, FC2, Cz). Magnitude is calculated as the average over electrodes, time, and frequency. These values represent the response during ignore condition.

Group	Value	95% CI
Auditory Control Enhancement (ACE)	-0.046	± 0.054
Sham tDCS + ACCT	0.043	± 0.106

Retention Primary · Through study completion, an average of 3 weeks

Percentage of enrolled participants who completed the study

Group	Value	95% CI
Auditory Control Enhancement (ACE)	7
Sham tDCS + ACCT	5

Blinding Primary · 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)?" Numbers reported indicate count of participants who selected "ACE".

Group	Value	95% CI
Auditory Control Enhancement (ACE)	5
Sham tDCS + ACCT	5

Acceptability Primary · Week 3

Acceptability rating on a visual analogue scale (0-100; greater = more acceptable) obtained via post-study survey.

Group	Value	95% CI
Auditory Control Enhancement (ACE)	89	± 7
Sham tDCS + ACCT	81	± 6

Change in MCCB Attention Scale Score Secondary · 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)

Group	Value	95% CI
Auditory Control Enhancement (ACE)	-2	± 5
Sham tDCS + ACCT	-3	± 8

Change in MCCB Processing Speed Scale Score Secondary · 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)

Group	Value	95% CI
Auditory Control Enhancement (ACE)	7	± 9
Sham tDCS + ACCT	-2	± 8

Change in Cerebral Blood Flow in Auditory Control Regions Primary · 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

Group	Value	95% CI
Auditory Control Enhancement (ACE)	3.25	± 8.00
Sham tDCS + ACCT	8.41	± 0

Sponsor's own description

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.

Publications & conference data

1 peer-reviewed publication reference this trial (live from Europe PMC):

1. Finding the Right Dose: NMDA Receptor-Modulating Treatments for Cognitive and Plasticity Deficits in Schizophrenia and the Role of Pharmacodynamic Target Engagement.
   Sehatpour P, Kantrowitz JT. · · 2025 · cited 12× · PMID 39218136 · DOI 10.1016/j.biopsych.2024.08.019