Recruiting
Phase 3

Modafinil & D-Serine

Sponsor:

University of Minnesota

Code:

NCT07263022

Conditions

Psychosis

Schizophrenia Disorder

Schizoaffective Disorder

Major Depressive Disorder With Psychotic Features

Bipolar Disorder With Psychotic Features

Eligibility Criteria

Sex: All

Age: 18 - 35

Healthy Volunteers: Not accepted

Interventions

Modafinil

D-serine solution

Placebo

Study Details

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

Conditions

Psychosis

Schizophrenia Disorder

Schizoaffective Disorder

Major Depressive Disorder With Psychotic Features

Bipolar Disorder With Psychotic Features

Study ID

NCT07263022

Start date

Jul 17, 2026

Status verified date

Jul, 2026

Completion date

Apr 30, 2030

Anticipated

Primary completion date

Apr 30, 2030

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18 - 35

Healthy Volunteers: Not accepted

Inclusion Criteria:

  • Between the ages of 18 and 35
  • Onset of a psychosis spectrum illness (schizophrenia, schizoaffective disorder, schizophreniform disorder, psychosis NOS, bipolar disorder with psychosis, or major depressive disorder with psychosis) within 5 years of enrollment
  • Estimated IQ of 70 or above
  • Proficient at English as determined through interactions with the study team
  • No change in psychiatric medication within a week of enrollment or MRI study visits
  • No clinically significant change in any medications for at least 1 month prior to study participation or MRI study visits, as determined by PI/Co-Is

  • Participants may have minor adjustments in medication doses in the past 30 days, per PI discretion, but may not have had major increases or decreases in doses, or additions or removal of medication within the past 30 days.
  • Participants are to have no changes to medications in the past 7 days before drug administration (i.e., must have been on a stable dose for at least 7 days prior to receiving the study drug).

Exclusion Criteria:

Medical Criteria:

  • Presence of the following medical concerns as determined by the study PI:

  • Major neurological disorder
  • History of a clinically significant head injury with or without prolonged unconsciousness
  • Any major medical condition that, in the opinion of the PI, would impede participation in the study or would put the participant at additional risk by participating
  • History of any of the following as reported by the participant:

  • Renal impairment, injury, or disease
  • Hepatic impairment, injury, or disease
  • Myocardial infarction or heart disease, or endorsement of history of or of cardiac symptoms at intake:

  • Dyspnea
  • Palpitations
  • Orthopnea
  • Pedal oedema
  • Significant dizziness
  • Syncope
  • Claudication
  • Low white blood cell count, or is diagnosed with leukopenia, neutropenia, or agranulocytosis
  • Presence of unmanaged hypertension (>140/90) or elevated resting heart rate (>100 bpm)
  • Abnormal clinical laboratory values:

  • uACR > 30 mg/g
  • creatinine level >0.95 mg/dL
  • AST or ALT > 50 U/L
  • Bilirubin > 1.2 mg/dL
  • Total Protein < 6 g/dL
  • Taking a medication or supplement that has a major drug interaction with any study drugs (e.g., ketamine, MAOIs, clomipramine, diazepam, propranolol, warfarin)
  • Allergies to study drugs
  • Is pregnant, planning to become pregnant, or is breastfeeding
  • Cannot pass the visual acuity test
  • Cannot pass the CMRR Subject Safety Screen due to MRI contraindications

Mental health criteria:

  • Meets criteria for a severe substance or alcohol use disorder within 3 months of enrollment
  • Lifetime history of a stimulant use disorder
  • Current manic episode as determined by the MINI
  • History of psychiatric hospitalization within 3 months of enrollment
  • Meets criteria for clinical risk of suicidal behavior, as defined by:

  • Clinician judgment
  • A suicide attempt within 3 months of enrollment
  • Active suicidal ideation at screening or baseline, as indicated by the C-SSRS Screener
  • Previous intent to act on suicidal ideation with a specific plan and/or preparatory acts within 3 months of enrollment, as indicated by the C-SSRS Screener
  • Symptom severity scores in the severe (6) or extremely severe (7) range on the BPRS for the following items: suicidality, disorientation, bizarre behavior, excitement, elevated mood
  • Any other psychiatric symptoms or conditions that, in the opinion of the PI, would impede participation in the study or put the participant at additional risk by participating

Other criteria:

  • Unable or unwilling to provide informed consent
  • Unable to demonstrate adequate decisional capacity, in the judgment of the consenting study staff member, to make a choice about participating in the research study
  • Current guardianship
  • Is under civil commitment or under a stay of civil commitment
  • Illiteracy
  • Has engaged in significant cognitive training, in the opinion of the PI, in the last year

Study Design

Enrollment

24 participants

Anticipated

Allocation

Randomized

Intervention Model

Crossover

Primary purpose

Basic Science

Interventions and Outcome Measures

Arms

experimental: Arm 1: Modafinil > d-serine > placebo

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)

experimental: Arm 2: Modafinil > placebo > d-serine

Participants will take single doses of three study medications in the following order: modafinil (200 mg); placebo; and d-serine (100 mg/kg). 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)

experimental: Arm 3: D-serine > modafinil > placebo

Participants will take single doses of three study medications in the following order: d-serine (100 mg/kg); modafinil (200 mg); 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)

experimental: Arm 4: D-serine > placebo > modafinil

Participants will take single doses of three study medications in the following order: d-serine (100 mg/kg); placebo; and modafinil (200 mg). 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)

experimental: Arm 5: Placebo > modafinil > d-serine

Participants will take single doses of three study medications in the following order: placebo; modafinil (200 mg); and d-serine (100 mg/kg). 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)

experimental: Arm 6: Placebo > d-serine > modafinil

Participants will take single doses of three study medications in the following order: placebo; d-serine (100 mg/kg); and modafinil (200 mg). 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)

Interventions

Modafinil

Single dose of modafinil capsule, 200 mg. Participants will also receive an oral placebo solution to maintain the blind.

D-serine solution

Single dose of oral solution of d-serine, 100 mg/kg. Participants will also receive a placebo capsule to maintain the blind.

Placebo

Single dose of oral placebo, in both capsule and oral solution

Primary outcome measure

  • Test My Brain - Digit Symbol Coding [ Time Frame: Baseline ]
  • Test My Brain - Digit Symbol Coding [ Time Frame: Day 7 (fMRI 1) ]
  • Test My Brain - Digit Symbol Coding [ Time Frame: Day 36 (fMRI 2) ]
  • Test My Brain - Digit Symbol Coding [ Time Frame: Day 63 (fMRI 3) ]
  • Test My Brain - Digit Symbol Coding [ Time Frame: Day 91 (fMRI 4) ]
  • Test My Brain - Digit Symbol Coding [ Time Frame: Day 119 (fMRI 5) ]
  • Test My Brain - Digit Symbol Coding [ Time Frame: Day 147 (fMRI 6) ]
  • Test My Brain - Verbal Paired Associates Memory [ Time Frame: Baseline ]
  • Test My Brain - Verbal Paired Associates Memory [ Time Frame: Day 7 (fMRI 1) ]
  • Test My Brain - Verbal Paired Associates Memory [ Time Frame: Day 36 (fMRI 2) ]
  • Test My Brain - Verbal Paired Associates Memory [ Time Frame: Day 63 (fMRI 3) ]
  • Test My Brain - Verbal Paired Associates Memory [ Time Frame: Day 91 (fMRI 4) ]
  • Test My Brain - Verbal Paired Associates Memory [ Time Frame: Day 119 (fMRI 5) ]
  • Test My Brain - Verbal Paired Associates Memory [ Time Frame: Day 147 (fMRI 6) ]
  • Test My Brain - Matrix Reasoning [ Time Frame: Baseline ]
  • Test My Brain - Matrix Reasoning [ Time Frame: Day 7 (fMRI 1) ]
  • Test My Brain - Matrix Reasoning [ Time Frame: Day 36 (fMRI 2) ]
  • Test My Brain - Matrix Reasoning [ Time Frame: Day 63 (fMRI 3) ]
  • Test My Brain - Matrix Reasoning [ Time Frame: Day 91 (fMRI 4) ]
  • Test My Brain - Matrix Reasoning [ Time Frame: Day 119 (fMRI 5) ]
  • Test My Brain - Matrix Reasoning [ Time Frame: Day 147 (fMRI 6) ]
  • Test My Brain - Multiracial Emotion Identification [ Time Frame: Baseline ]
  • Test My Brain - Multiracial Emotion Identification [ Time Frame: Day 7 (fMRI 1) ]
  • Test My Brain - Multiracial Emotion Identification [ Time Frame: Day 36 (fMRI 2) ]
  • Test My Brain - Multiracial Emotion Identification [ Time Frame: Day 63 (fMRI 3) ]
  • Test My Brain - Multiracial Emotion Identification [ Time Frame: Day 91 (fMRI 4) ]
  • Test My Brain - Multiracial Emotion Identification [ Time Frame: Day 119 (fMRI 5) ]
  • Test My Brain - Multiracial Emotion Identification [ Time Frame: Day 147 (fMRI 6) ]
  • Resting-state functional connectivity [ Time Frame: Day 7 (fMRI 1) ]
  • Resting-state functional connectivity [ Time Frame: Day 36 (fMRI 2) ]
  • Resting-state functional connectivity [ Time Frame: Day 63 (fMRI 3) ]
  • Resting-state functional connectivity [ Time Frame: Day 91 (fMRI 4) ]
  • Resting-state functional connectivity [ Time Frame: Day 119 (fMRI 5) ]
  • Resting-state functional connectivity [ Time Frame: Day 147 (fMRI 6) ]
  • Dot Pattern Expectancy variation (TOPX) task performance [ Time Frame: Day 7 (fMRI 1) ]
  • Dot Pattern Expectancy variation (TOPX) task performance [ Time Frame: Day 36 (fMRI 2) ]
  • Dot Pattern Expectancy variation (TOPX) task performance [ Time Frame: Day 63 (fMRI 3) ]
  • Dot Pattern Expectancy variation (TOPX) task performance [ Time Frame: Day 91 (fMRI 4) ]
  • Dot Pattern Expectancy variation (TOPX) task performance [ Time Frame: Day 119 (fMRI 5) ]
  • Dot Pattern Expectancy variation (TOPX) task performance [ Time Frame: Day 147 (fMRI 6) ]
  • Translational Bandit Task (TBT) Performance [ Time Frame: Day 7 (fMRI 1) ]
  • Translational Bandit Task (TBT) Performance [ Time Frame: Day 36 (fMRI 2) ]
  • Translational Bandit Task (TBT) Performance [ Time Frame: Day 63 (fMRI 3) ]
  • Translational Bandit Task (TBT) Performance [ Time Frame: Day 91 (fMRI 4) ]
  • Translational Bandit Task (TBT) Performance [ Time Frame: Day 119 (fMRI 5) ]
  • Translational Bandit Task (TBT) Performance [ Time Frame: Day 147 (fMRI 6) ]

Central Contacts and Locations

Central contacts

Freddie Holmberg Kohler, MBS, CCRP

612-772-2201costep2@umn.edu

Ariel Currie

curri105@umn.edu

Locations

University of Minnesota

Recruiting

Minneapolis, Minnesota, United States, 55455

Contacts

Ariel Currie, MBS, CCRP

curri105@umn.edu

More Information

Sponsor

University of Minnesota

Last update posted

Jul 23, 2026

Last verified

Jul, 2026

Keywords

  • Cognition
  • Decision Making
  • fMRI
  • Psychosis spectrum disorders

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by University of Minnesota on 2026-07-23.