Cognitive Strategies in Early Psychosis 2

NCT ID: NCT07263022

Last Updated: 2025-12-19

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

NOT_YET_RECRUITING

Clinical Phase

PHASE3

Total Enrollment

24 participants

Study Classification

INTERVENTIONAL

Study Start Date

2026-02-01

Study Completion Date

2030-04-30

Brief Summary

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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

Detailed Description

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Participants will be asked to complete ten appointments in this study: An intake appointment, 6 functional Magnetic Resonance Imaging (fMRI) appointments, and 3 clinical interview appointments. In addition, there will be 3 brief clinical check ins, and 6 phone call check ins after fMRI appointments.

Intake Appointment:

The first appointment is the Intake appointment. This visit will take between 1.75-2.75 hours, depending on how many study tasks are needed. Participants in this study may have participated in a sister study, called "State Representation in Early Psychosis 2 (STEP 2)." If so, they will not need to complete many of the intake questionnaires, and it is expected to take about 100 minutes for them to complete this appointment. If they did not participate in STEP 2, participants will need to complete the full intake battery.

During the interview, the investigators will ask questions about a participant's medical and psychiatric history, and current and past mental health symptoms. They will collect demographics, as well as information on the person's social life and quality of life. Participants will also provide a blood sample for clinical safety screening. The investigators will collect one 3mL tube, which is less than 2/3 of a teaspoon. If pregnancy is a physical possibility, they will also collect a urine sample for pregnancy testing.

fMRI Appointments: The second appointment is an fMRI + study agent appointment. Participants will come in person to the University of Minnesota Center for Magnetic Resonance Research. This visit will take about 7-7.5 hours.

First, the investigators will complete safety screening measures. This will include:

* A screening questionnaire to make sure the participant can enter the fMRI machine safely
* A blood pressure reading.
* A vision test.
* A breathalyzer to test for the presence of alcohol.
* A urine drug test to screen for the presence of substances.
* If pregnancy is a physical possibility, a urine pregnancy test will be required.

After screening measures are successfully completed, participants will complete the brain games on a computer. Afterwards, the participant will enter the fMRI machine. The very first fMRI scan will last 2 hours, as the investigators will get additional pictures for the structure of the brain before the scan that measures brain activity.

After this, the participant will take a single dose of the study agent. Neither the participant nor the study team will know which study agent the participant is taking. They will be randomly assigned to one of six schedules (for example, one participant will have A \> B \> C, and another will have A \> C \> B, and so on). The participant will be provided with a meal while the study agent metabolizes. Afterwards, the investigators will monitor the participant's vital signs and ask whether they are experiencing any adverse effects.

After the observation period is completed, the participant will complete a second fMRI scan. This scan will last 90 minutes. Afterwards, they will play the same brain games on the computer. The investigators will take another vital sign measurement and ask about adverse effects.

The following day, the investigators will contact the participant via phone to ask whether they experienced any adverse effects after leaving the study appointment. This call should last about 5 minutes.

The remaining 5 fMRI visits will be the same, except that the first scan of the day will be only 90 minutes long. fMRI appointments will be scheduled approximately one month apart.

Clinical Interview Appointments:

Between fMRIs 1 and 2, 3 and 4, and 5 and 6, the investigators will interview participants to ask questions about their current mental health symptoms, their quality of life, and their social life. Participants will also complete self-report questionnaires which cover the same topics. These appointments will take about 90 minutes. The appointment can be completed in person at the University of Minnesota or remotely via Zoom.

Between fMRIs 2 and 3, and 4 and 5, participants will be asked a brief series of questions about their recent mental health symptoms. This will be a remote visit conducted via Zoom or by phone. These calls should take about 20 minutes.

Conditions

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

Keywords

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Cognition Decision Making fMRI Psychosis spectrum disorders

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

Each participant will take a single dose of each drug 2 times. There will be 6 different orders of administration (e.g., A\>B\>C, A\>C\>B).
Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

TRIPLE

Participants Investigators Outcome Assessors

Study Groups

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Arm 1: Modafinil > d-serine > placebo

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

Group Type EXPERIMENTAL

Modafinil

Intervention Type DRUG

Single dose of modafinil capsule, 100 mg. Participants will also receive an oral placebo solution to maintain the blind.

D-serine solution

Intervention Type DRUG

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

Placebo

Intervention Type DRUG

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

Arm 2: Modafinil > placebo > d-serine

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

Group Type EXPERIMENTAL

Modafinil

Intervention Type DRUG

Single dose of modafinil capsule, 100 mg. Participants will also receive an oral placebo solution to maintain the blind.

D-serine solution

Intervention Type DRUG

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

Placebo

Intervention Type DRUG

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

Arm 3: D-serine > modafinil > placebo

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

Group Type EXPERIMENTAL

Modafinil

Intervention Type DRUG

Single dose of modafinil capsule, 100 mg. Participants will also receive an oral placebo solution to maintain the blind.

D-serine solution

Intervention Type DRUG

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

Placebo

Intervention Type DRUG

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

Arm 4: D-serine > placebo > modafinil

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

Group Type EXPERIMENTAL

Modafinil

Intervention Type DRUG

Single dose of modafinil capsule, 100 mg. Participants will also receive an oral placebo solution to maintain the blind.

D-serine solution

Intervention Type DRUG

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

Placebo

Intervention Type DRUG

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

Arm 5: Placebo > modafinil > d-serine

Participants will take single doses of three study medications in the following order: placebo; modafinil (100 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)

Group Type EXPERIMENTAL

Modafinil

Intervention Type DRUG

Single dose of modafinil capsule, 100 mg. Participants will also receive an oral placebo solution to maintain the blind.

D-serine solution

Intervention Type DRUG

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

Placebo

Intervention Type DRUG

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

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 (100mg). 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)

Group Type EXPERIMENTAL

Modafinil

Intervention Type DRUG

Single dose of modafinil capsule, 100 mg. Participants will also receive an oral placebo solution to maintain the blind.

D-serine solution

Intervention Type DRUG

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

Placebo

Intervention Type DRUG

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

Interventions

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Modafinil

Single dose of modafinil capsule, 100 mg. Participants will also receive an oral placebo solution to maintain the blind.

Intervention Type DRUG

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.

Intervention Type DRUG

Placebo

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

Intervention Type DRUG

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

35 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Institute of Mental Health (NIMH)

NIH

Sponsor Role collaborator

University of Minnesota

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Sophia Vinogradov, MD

Role: PRINCIPAL_INVESTIGATOR

University of Minnesota Department of Psychiatry and Behavioral Sciences

Caroline Demro, Ph.D.

Role: PRINCIPAL_INVESTIGATOR

University of Minnesota Department of Psychiatry and Behavioral Sciences

Central Contacts

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Freddie Holmberg Kohler

Role: CONTACT

Phone: 612-772-2201

Email: [email protected]

Other Identifiers

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P50MH119569

Identifier Type: NIH

Identifier Source: secondary_id

View Link

STUDY00025575

Identifier Type: -

Identifier Source: org_study_id