Brief Summary

The goal of this clinical trial is to learn more about decision making in psychosis spectrum disorders, like schizophrenia. Participants will be people who have had symptoms of a psychosis spectrum disorder start within the last five years. The investigators will study how two study agents change decision making in people with psychosis, by asking participants to complete some brain games on the computer before and after taking the study agents. The investigators hope to improve our understanding of psychosis to help people in the future. The main research questions are:

Does a single dose of modafinil change how people with psychosis play the brain games?
Does a single dose of d-serine change how people with psychosis play the brain games?
Does a single dose of modafinil change brain activity?
Does a single dose of d-serine change brain activity? Participants will:
Complete an interview and self-report questionnaires.
Complete safety screening activities, like a blood draw, a urine drug test, and an alcohol breathalyzer test.
Complete functional Magnetic Resonance Imaging (fMRI) scans. fMRI uses magnets to take pictures of the brain. There will be six scanning appointments in the study, with two scans each. Appointments will be about a month apart.
Take a single dose of a study agent during each scanning appointment. The study agent will be taken after the first fMRI. There are three study agents in total: modafinil, d-serine, and a placebo. Each participant will take each study agent twice during the study.
Play brain games on a computer that measure decision making, thinking, and problem solving skills

Trial Health

Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment

participants targeted

Target at below P25 for phase_3

Timeline

48mo left

Started May 2026

Typical duration for phase_3

Status

not yet recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

4 years study duration

First Submitted

Initial submission to the registry

August 25, 2025

Completed

3 months until next milestone

First Posted

Study publicly available on registry

December 4, 2025

Completed

5 months until next milestone

Study Start

First participant enrolled

May 11, 2026

Expected

4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

April 30, 2030

Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

April 30, 2030

Last Updated

April 15, 2026

Status Verified

April 1, 2026

Enrollment Period

4 years

First QC Date

August 25, 2025

Last Update Submit

April 14, 2026

Conditions

Cognition Psychosis Schizoaffective Disorder Major Depressive Disorder With Psychotic Features Bipolar Disorder With Psychotic Features Psychosis NOS Schizophreniform Disorder Psychotic Disorder Schizophrenia Disorder

Keywords

CognitionDecision MakingfMRIPsychosis spectrum disorders

Outcome Measures

Primary Outcomes (46)

Test My Brain - Digit Symbol Coding
A computerized cognitive assessment measuring processing speed. Z scores range from -5 to 5, with a higher score indicating increased cognitive functioning.
Baseline
Test My Brain - Digit Symbol Coding
A computerized cognitive assessment measuring processing speed. Z scores range from -5 to 5, with a higher score indicating increased cognitive functioning.
Day 7 (fMRI 1)
Test My Brain - Digit Symbol Coding
A computerized cognitive assessment measuring processing speed. Z scores range from -5 to 5, with a higher score indicating increased cognitive functioning.
Day 36 (fMRI 2)
Test My Brain - Digit Symbol Coding
A computerized cognitive assessment measuring processing speed. Z scores range from -5 to 5, with a higher score indicating increased cognitive functioning.
Day 63 (fMRI 3)
Test My Brain - Digit Symbol Coding
A computerized cognitive assessment measuring processing speed. Z scores range from -5 to 5, with a higher score indicating increased cognitive functioning.
Day 91 (fMRI 4)
Test My Brain - Digit Symbol Coding
A computerized cognitive assessment measuring processing speed. Z scores range from -5 to 5, with a higher score indicating increased cognitive functioning.
Day 119 (fMRI 5)
Test My Brain - Digit Symbol Coding
A computerized cognitive assessment measuring processing speed. Z scores range from -5 to 5, with a higher score indicating increased cognitive functioning.
Day 147 (fMRI 6)
Test My Brain - Verbal Paired Associates Memory
A computerized cognitive assessment measuring verbal memory. Z scores range from -5 to 5, with a higher score indicating increased cognitive functioning.
Baseline
Test My Brain - Verbal Paired Associates Memory
A computerized cognitive assessment measuring verbal memory. Z scores range from -5 to 5, with a higher score indicating increased cognitive functioning.
Day 7 (fMRI 1)
Test My Brain - Verbal Paired Associates Memory
A computerized cognitive assessment measuring verbal memory. Z scores range from -5 to 5, with a higher score indicating increased cognitive functioning.
Day 36 (fMRI 2)
Test My Brain - Verbal Paired Associates Memory
A computerized cognitive assessment measuring verbal memory. Z scores range from -5 to 5, with a higher score indicating increased cognitive functioning.
Day 63 (fMRI 3)
Test My Brain - Verbal Paired Associates Memory
A computerized cognitive assessment measuring verbal memory. Z scores range from -5 to 5, with a higher score indicating increased cognitive functioning.
Day 91 (fMRI 4)
Test My Brain - Verbal Paired Associates Memory
A computerized cognitive assessment measuring verbal memory. Z scores range from -5 to 5, with a higher score indicating increased cognitive functioning.
Day 119 (fMRI 5)
Test My Brain - Verbal Paired Associates Memory
A computerized cognitive assessment measuring verbal memory. Z scores range from -5 to 5, with a higher score indicating increased cognitive functioning.
Day 147 (fMRI 6)
Test My Brain - Matrix Reasoning
A computerized cognitive assessment measuring problem solving. Z scores range from -5 to 5, with a higher score indicating increased cognitive functioning.
Baseline
Test My Brain - Matrix Reasoning
A computerized cognitive assessment measuring problem solving. Z scores range from -5 to 5, with a higher score indicating increased cognitive functioning.
Day 7 (fMRI 1)
Test My Brain - Matrix Reasoning
A computerized cognitive assessment measuring problem solving. Z scores range from -5 to 5, with a higher score indicating increased cognitive functioning.
Day 36 (fMRI 2)
Test My Brain - Matrix Reasoning
A computerized cognitive assessment measuring problem solving. Z scores range from -5 to 5, with a higher score indicating increased cognitive functioning.
Day 63 (fMRI 3)
Test My Brain - Matrix Reasoning
A computerized cognitive assessment measuring problem solving. Z scores range from -5 to 5, with a higher score indicating increased cognitive functioning.
Day 91 (fMRI 4)
Test My Brain - Matrix Reasoning
A computerized cognitive assessment measuring problem solving. Z scores range from -5 to 5, with a higher score indicating increased cognitive functioning.
Day 119 (fMRI 5)
Test My Brain - Matrix Reasoning
A computerized cognitive assessment measuring problem solving. Z scores range from -5 to 5, with a higher score indicating increased cognitive functioning.
Day 147 (fMRI 6)
Test My Brain - Multiracial Emotion Identification
A computerized cognitive assessment measuring social cognition and emotion recognition skills. Z scores range from -5 to 5, with a higher score indicating increased cognitive functioning.
Baseline
Test My Brain - Multiracial Emotion Identification
A computerized cognitive assessment measuring social cognition and emotion recognition skills. Z scores range from -5 to 5, with a higher score indicating increased cognitive functioning.
Day 7 (fMRI 1)
Test My Brain - Multiracial Emotion Identification
A computerized cognitive assessment measuring social cognition and emotion recognition skills. Z scores range from -5 to 5, with a higher score indicating increased cognitive functioning.
Day 36 (fMRI 2)
Test My Brain - Multiracial Emotion Identification
A computerized cognitive assessment measuring social cognition and emotion recognition skills. Z scores range from -5 to 5, with a higher score indicating increased cognitive functioning.
Day 63 (fMRI 3)
Test My Brain - Multiracial Emotion Identification
A computerized cognitive assessment measuring social cognition and emotion recognition skills. Z scores range from -5 to 5, with a higher score indicating increased cognitive functioning.
Day 91 (fMRI 4)
Test My Brain - Multiracial Emotion Identification
A computerized cognitive assessment measuring social cognition and emotion recognition skills. Z scores range from -5 to 5, with a higher score indicating increased cognitive functioning.
Day 119 (fMRI 5)
Test My Brain - Multiracial Emotion Identification
A computerized cognitive assessment measuring social cognition and emotion recognition skills. Z scores range from -5 to 5, with a higher score indicating increased cognitive functioning.
Day 147 (fMRI 6)
Resting-state functional connectivity
Resting state connectivity in the brain is measured with fMRI. The primary outcome will be changes in resting-state functional connectivity before and after study agent administration
Day 7 (fMRI 1)
Resting-state functional connectivity
Resting state connectivity in the brain is measured with fMRI. The primary outcome will be changes in resting-state functional connectivity before and after study agent administration
Day 36 (fMRI 2)
Resting-state functional connectivity
Resting state connectivity in the brain is measured with fMRI. The primary outcome will be changes in resting-state functional connectivity before and after study agent administration
Day 63 (fMRI 3)
Resting-state functional connectivity
Resting state connectivity in the brain is measured with fMRI. The primary outcome will be changes in resting-state functional connectivity before and after study agent administration
Day 91 (fMRI 4)
Resting-state functional connectivity
Resting state connectivity in the brain is measured with fMRI. The primary outcome will be changes in resting-state functional connectivity before and after study agent administration
Day 119 (fMRI 5)
Resting-state functional connectivity
Resting state connectivity in the brain is measured with fMRI. The primary outcome will be changes in resting-state functional connectivity before and after study agent administration
Day 147 (fMRI 6)
Dot Pattern Expectancy variation (TOPX) task performance
The TOPX task consists of a series of pattern sequences. One pattern is designated the "A" cue, and another the "X" cue, which requires one response (AX, 60-70% of trials, e.g. respond with the left button), while other sequences require a different response (AY or BX, 12-15% of trials each, or BY, 6-10% of trials, e.g. respond with the right button). Given the strong expectation that X's evokes a valid response, BX trials place demands on the fidelity (stability, memory) of the "B" cue state representation to overcome this tendency. Performance is assessed based on accuracy and response time. The primary outcome will be differences in task performance before and after modafinil administration.
Day 7 (fMRI 1)
Dot Pattern Expectancy variation (TOPX) task performance
The TOPX task consists of a series of pattern sequences. One pattern is designated the "A" cue, and another the "X" cue, which requires one response (AX, 60-70% of trials, e.g. respond with the left button), while other sequences require a different response (AY or BX, 12-15% of trials each, or BY, 6-10% of trials, e.g. respond with the right button). Given the strong expectation that X's evokes a valid response, BX trials place demands on the fidelity (stability, memory) of the "B" cue state representation to overcome this tendency. Performance is assessed based on accuracy and response time. The primary outcome will be differences in task performance before and after modafinil administration.
Day 36 (fMRI 2)
Dot Pattern Expectancy variation (TOPX) task performance
The TOPX task consists of a series of pattern sequences. One pattern is designated the "A" cue, and another the "X" cue, which requires one response (AX, 60-70% of trials, e.g. respond with the left button), while other sequences require a different response (AY or BX, 12-15% of trials each, or BY, 6-10% of trials, e.g. respond with the right button). Given the strong expectation that X's evokes a valid response, BX trials place demands on the fidelity (stability, memory) of the "B" cue state representation to overcome this tendency. Performance is assessed based on accuracy and response time. The primary outcome will be differences in task performance before and after modafinil administration.
Day 63 (fMRI 3)
Dot Pattern Expectancy variation (TOPX) task performance
The TOPX task consists of a series of pattern sequences. One pattern is designated the "A" cue, and another the "X" cue, which requires one response (AX, 60-70% of trials, e.g. respond with the left button), while other sequences require a different response (AY or BX, 12-15% of trials each, or BY, 6-10% of trials, e.g. respond with the right button). Given the strong expectation that X's evokes a valid response, BX trials place demands on the fidelity (stability, memory) of the "B" cue state representation to overcome this tendency. Performance is assessed based on accuracy and response time. The primary outcome will be differences in task performance before and after modafinil administration.
Day 91 (fMRI 4)
Dot Pattern Expectancy variation (TOPX) task performance
The TOPX task consists of a series of pattern sequences. One pattern is designated the "A" cue, and another the "X" cue, which requires one response (AX, 60-70% of trials, e.g. respond with the left button), while other sequences require a different response (AY or BX, 12-15% of trials each, or BY, 6-10% of trials, e.g. respond with the right button). Given the strong expectation that X's evokes a valid response, BX trials place demands on the fidelity (stability, memory) of the "B" cue state representation to overcome this tendency. Performance is assessed based on accuracy and response time. The primary outcome will be differences in task performance before and after modafinil administration.
Day 119 (fMRI 5)
Dot Pattern Expectancy variation (TOPX) task performance
The TOPX task consists of a series of pattern sequences. One pattern is designated the "A" cue, and another the "X" cue, which requires one response (AX, 60-70% of trials, e.g. respond with the left button), while other sequences require a different response (AY or BX, 12-15% of trials each, or BY, 6-10% of trials, e.g. respond with the right button). Given the strong expectation that X's evokes a valid response, BX trials place demands on the fidelity (stability, memory) of the "B" cue state representation to overcome this tendency. Performance is assessed based on accuracy and response time. The primary outcome will be differences in task performance before and after modafinil administration.
Day 147 (fMRI 6)
Translational Bandit Task (TBT) Performance
This is a task variant that uses choice options (neutral images) that are rewarded probabilistically. The rewarded stimulus with the highest reward is changed over time. State learning associated with staying or switching stimuli too quickly (lose-switching) can be evaluated. Performance is assessed based on accuracy, response time, and behavior of reward seeking. The primary outcome will be differences in task performance before and after modafinil administration.
Day 7 (fMRI 1)
Translational Bandit Task (TBT) Performance
This is a task variant that uses choice options (neutral images) that are rewarded probabilistically. The rewarded stimulus with the highest reward is changed over time. State learning associated with staying or switching stimuli too quickly (lose-switching) can be evaluated. Performance is assessed based on accuracy, response time, and behavior of reward seeking. The primary outcome will be differences in task performance before and after modafinil administration.
Day 36 (fMRI 2)
Translational Bandit Task (TBT) Performance
This is a task variant that uses choice options (neutral images) that are rewarded probabilistically. The rewarded stimulus with the highest reward is changed over time. State learning associated with staying or switching stimuli too quickly (lose-switching) can be evaluated. Performance is assessed based on accuracy, response time, and behavior of reward seeking. The primary outcome will be differences in task performance before and after modafinil administration.
Day 63 (fMRI 3)
Translational Bandit Task (TBT) Performance
This is a task variant that uses choice options (neutral images) that are rewarded probabilistically. The rewarded stimulus with the highest reward is changed over time. State learning associated with staying or switching stimuli too quickly (lose-switching) can be evaluated. Performance is assessed based on accuracy, response time, and behavior of reward seeking. The primary outcome will be differences in task performance before and after modafinil administration.
Day 91 (fMRI 4)
Translational Bandit Task (TBT) Performance
This is a task variant that uses choice options (neutral images) that are rewarded probabilistically. The rewarded stimulus with the highest reward is changed over time. State learning associated with staying or switching stimuli too quickly (lose-switching) can be evaluated. Performance is assessed based on accuracy, response time, and behavior of reward seeking. The primary outcome will be differences in task performance before and after modafinil administration.
Day 119 (fMRI 5)
Translational Bandit Task (TBT) Performance
This is a task variant that uses choice options (neutral images) that are rewarded probabilistically. The rewarded stimulus with the highest reward is changed over time. State learning associated with staying or switching stimuli too quickly (lose-switching) can be evaluated. Performance is assessed based on accuracy, response time, and behavior of reward seeking. The primary outcome will be differences in task performance before and after modafinil administration.
Day 147 (fMRI 6)

Secondary Outcomes (9)

Brief Psychiatric Rating Scale (BPRS) - Global Score
Baseline
Brief Psychiatric Rating Scale (BPRS) - Global Score
Day 21 (Clinical A)
Brief Psychiatric Rating Scale (BPRS) - Global Score
Day 49 (Brief Clinical B)
Brief Psychiatric Rating Scale (BPRS) - Global Score
Day 77 (Clinical C)
Brief Psychiatric Rating Scale (BPRS) - Global Score
Day 105 (Brief Clinical D)
+4 more secondary outcomes

Other Outcomes (9)

Abbreviated Quality of Life Scale (aQLS) - Global Score
Day 21 (Clinical A)
Abbreviated Quality of Life Scale (aQLS) - Global Score
Day 77 (Clinical C)
Abbreviated Quality of Life Scale (aQLS) - Global Score
Day 133 (Clinical E)
+6 more other outcomes

Study Arms (6)

Arm 1: Modafinil > d-serine > placebo

EXPERIMENTAL

Participants will take single doses three study medications in the following order: modafinil (200 mg); d-serine (100 mg/kg); and placebo. All medications will be taken 2 times (A\>B\>C\>A\>B\>C). (Note: This order is not necessarily reflective of the actual randomization schedule used in the protocol, as the procedure is double-blinded)