Cognitive strategies for early psychosis.

Cognitive Strategies in Early Psychosis 1

This will try a single dose of modafinil in people without psychosis to see if it changes how they play decision-making brain games and their brain activity.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 103 (estimated)
• Ages: 18 Years to 35 Years
• Sex: All
• Sponsor: University of Minnesota (Academic / other)
• Locations: 1 site (Minneapolis, Minnesota)
• Trial ID: NCT07231497 on ClinicalTrials.gov

What this trial studies

Participants complete two in-person visits roughly one week apart: an intake visit with interviews and questionnaires, and a longer EEG + medication visit at the University of Minnesota. At the EEG visit participants undergo safety screening (blood draw, urine drug test, breathalyzer), wear an EEG cap, complete computerized decision-making tasks, and receive a single dose of modafinil with repeat task/EEG recordings. Visits take about 30 minutes to 2.5 hours for intake (shorter if they participated in a sister study) and about 4–4.5 hours for the EEG/medication visit. The design compares task performance and EEG signals before and after the single modafinil dose to see acute drug-related changes.

Who should consider this trial

Good fit: Adults who do not have psychosis, speak English, have estimated IQ ≥70, can attend two in-person visits, and have been clinically stable on any medications per study rules are the intended participants.

Not a fit: People with major neurological disorders, certain medical contraindications to modafinil, unstable psychiatric status, or who cannot travel to Minneapolis likely would not benefit or be eligible.

Why it matters

Potential benefit: If successful, the results could improve understanding of decision-making brain processes relevant to psychosis and inform future treatment or cognitive interventions.

How similar studies have performed: Prior studies of modafinil for cognition and EEG have shown mixed but sometimes positive effects, so this approach builds on existing but not definitive evidence.

Eligibility criteria

Inclusion Criteria:

* English proficiency, as determined by staff observation and participant self-report
* Estimated IQ at or above 70, as estimated by the cognitive assessments
* Is clinical stable, defined as outpatient status for at least one month prior to study participation
* Has clinically stable doses of medication for at least one month prior to study participation as determined by the PI

  * Participants may have minor adjustments in medication doses in the past 30 days, per PI discretion, but may not have major increases or decreases in dosses, or additions or removal of medications in the past 30 days
  * Participants are to have no changes to medications in the past 7 days before study medication 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 head injury with or without prolonged consciousness
  * 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.
* The following cardiac symptoms requiring medical follow-up that, in the opinion of the investigator, would impede participation in the study or would put the participant at additional risk by participating

  * Dsypnea
  * 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
* Participant is pregnant, planning to become pregnant, or is breastfeeding
* Participant cannot pass the visual acuity test (e.g., a score lower than 20/25 on the Snellen)
* Takes medications or supplements that have major interactions with modafinil (e.g., ketamine, MAOIs, clomipramine, diazepam, propranolol, warfarin, amphetamine or dextroamphetamine, dexmethylphenidate or methylphenidate)
* Has an allergy to modafinil
* Is currently taking modafinil as a prescription
* Has previously experienced Stevens-Johnson syndrome in response to taking a medication

Mental health criteria:

* Meets criteria for severe substance or alcohol use disorder within 3 months of enrollment
* Lifetime history of stimulant use disorder
* Meets criteria for clinical risk of suicidal behavior, as defined by:

  * Clinician judgment
  * Active suicidal ideation at screening or other appointments
  * Previous intent to act on suicidal ideation with a specific plan and/or preparatory acts within 6 months of enrollment
  * A suicide attempt within 6 months of enrollment
* Meets criteria for a depressive episode within the past month as determined by the diagnostic interview or for a severe or extremely severe depressive episode in the abbreviated battery within the past month
* Meets DSM-5 criteria for, or reports professional diagnosis of, a psychotic, bipolar, or autism spectrum disorder
* Has a family history (1st degree relative) of psychotic, bipolar, or autism spectrum disorder
* Is prescribed psychotropic medications or takes supplements with psychotropic effects (e.g., Nootropics)
* 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
* Participant is illiterate
* Have engaged in significant cognitive training, in the opinion of the PI, in the last year

Where this trial is running

Minneapolis, Minnesota

• University of Minnesota — Minneapolis, Minnesota, United States (Recruiting)

Study contacts

• Principal investigator: Sophia Vinogradov, MD — University of Minnesota
• Study coordinator: Kaylee Enevold

Conditions Cognition; Healthy Participants; Decision making; Electroencephalography; Psychosis