R33: Levetiracetam in Early Psychosis

May 26, 2026 updated by: NYU Langone Health

A 12-week Randomized, Double-blind, Placebo-controlled Trial Investigating the Effects of Levetiracetam in Early Psychosis

This is a 12-week study of levetiracetam added to a second generation antipsychotic in early psychosis patients who have been ill for less than 5 years and continue to experience psychotic symptoms despite at least 8 weeks of antipsychotic treatment. Levetiracetam (Keppra) is a medication approved for the treatment of epilepsy; it reduces excessive activity in the brain. This study will test the hypotheses that adding levetiracetam will improve psychotic symptoms that are unresponsive to antipsychotic treatment and will protect the brain from atrophy (volume loss). .

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Participants will complete screening and baseline visits before being randomized in a 2:1 ratio to levetiracetam or placebo added to the antipsychotic medication. They will complete weekly study visits for the first 4 weeks (Baseline, Weeks 2-4) and then additional visits at Week 6, 8, and 12. Participants will be studied both by assessing change in symptom severity and cognitive performance over the 12 weeks as well as using an imaging measure of hippocampal volume integrity at baseline and week 12. After completing Week 12 or decision to withdraw prematurely from the study, participants will complete a 9 day medication tapering regimen.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
65

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • United States
    • New York
      • New York, New York, United States, 10016
        • NYU Langone Health

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

16 years to 40 years (Child, Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria

  • Males and females 16 to 40 years of age, inclusive, at time of informed consent
  • Must have experienced a first episode of nonaffective psychosis within 5 years and exhibit current psychosis, as defined by a score of ≥ 4 on one of the following psychosis items on the BPRS: conceptual disorganization, suspiciousness, hallucinations, unusual thought content, or grandiosity, for at least 4 days per week for at least 4 weeks
  • Must have a diagnosis of either schizophrenia, schizoaffective disorder or schizophreniform disorder as established by a Structured Clinical Interview for DSM-V (SCID)
  • Must have taken antipsychotic medication for a minimum of 8 weeks and at a stable dose for at least 4 weeks prior to randomization

  • If assigned female at birth and of childbearing potential, patients must:

    • Have a negative urine pregnancy test (all participants assigned female at birth regardless of childbearing potential will be required to submit a pregnancy test) and
    • Not be nursing or planning a pregnancy for the duration of the study through 30 days after the last dosing visit and
    • Be abstinent or willing to use a reliable method of birth control from the screening visit and continue with the same method until termination from the study

Exclusion Criteria

  • Current substance abuse or dependence for substances other than nicotine and THC (i.e. alcohol, amphetamines, barbiturates)

    • A positive urine toxic screen (excluding THC, tricyclic antidepressants, or benzodiazepines (if prescribed))
    • Moderate or severe cannabis use disorder
  • Diagnosis of major mood disorder or other Axis I disorder other than Schizophrenia, Schizoaffective Disorder or Schizophreniform Disorder
  • Current suicidal ideation. Suicidal ideation with intent or plan (indicated by affirmative answers to items 4 or 5 of the suicidal ideation section of the baseline C-SSRS) in the 6 months prior to screening or subjects who represent a significant risk of suicide in the opinion of the Principal Investigator
  • Pregnant, nursing or positive urine pregnancy test
  • Significant medical or neurological illness by history or physical exam including seizure disorder, history of loss of consciousness related to head trauma or developmental disorder including mental retardation
  • Renal insufficiency (if serum creatinine is greater than laboratory limits for normal, estimated creatinine clearance must be greater than 80)
  • Contraindications to MRI: metal implants, pacemaker, or other metal in the body, or claustrophobia. Individuals with tattoos will be excluded from imaging if tattoos cover more than 5% of the body surface, if a tattoo is greater than 20 cm, or if the tattoo is located on the face, neck or genitals. (Individuals with a contraindication to MRI may participate in the trial but will be excluded from the elective MRI component)

  • Significant history of serious violence

    • For both inpatient and outpatient subjects, a history of serious violence as assessed by the Buss-Perry Aggression Questionnaire
    • For outpatient subjects only, a score of 5 (moderately severe) or higher on the BPRS hostility item at screening or baseline

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Active Comparator: Study Drug group
Participants in this group will receive 500 mg of levetiracetam twice daily for 12 weeks. After 12 weeks, levetiracetam will be gradually decreased and stopped over the next 9 days. Questionnaires will be administered at each visit to examine how participants are responding to the treatment. In addition, a brain scan and cognitive testing will be performed when feasible at the beginning and the end of the study.
Drug: Levetiracetam Pill
Levetiracetam is an anticonvulsant that is frequently used to treat epilepsy in children and adults due to its superior tolerability, ease of use and excellent safety profile. It is rapidly absorbed and rapidly crosses the blood-brain barrier. Levetiracetam does not affect metabolism of antipsychotic drugs and may normalize hippocampal hyperactivity by decreasing excessive glutamatergic and dopaminergic transmission, thereby making it an ideal agent to test the hypothesis that reducing excessive hippocampal activity may enhance treatment of early psychosis and prevent antipsychotic toxicity. Levetiracetam will be administered in 500 mg capsules twice a day.
Other Names:
  • Keppra
Placebo Comparator: Placebo Group
Participants in this group will receive a placebo that looks like the levetiracetam pill twice daily for 12 weeks. After 12 weeks, the levetiracetam dose will be tapered for the next 9 days. Questionnaires will be administered at each visit to examine how participants are responding to the treatment. In addition, a brain scan and cognitive testing will be performed when feasible at the beginning and the end of the study.
Other: Placebo
The placebo pill (sugar pill) will look just like the levetiracetam pill but does not contain levetiracetam. Placebo will be taken along with optimal antipsychotic medication selected by either the outpatient provider or the hospital staff responsible for the participant's care. Participants will be instructed to take the placebo pill twice daily for 12 weeks.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Change in BPRS total score
Time Frame: Baseline visit (week 0), Week 12 visit
The efficacy of levetiracetam 500 mg bid vs. placebo on symptoms will be measured by the BPRS total score. Brief Psychiatric Rating Scale (BPRS) is an 18-item scale that measures positive symptoms, negative symptoms, general psychopathology and affective symptoms. Individual items are scored on a seven point likert scale. The total score is the sum of responses and ranges from 18 to 126; a higher score on the BPRS items indicates increased severity of symptoms.
Baseline visit (week 0), Week 12 visit

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Change in BPRS Psychosis Subscale
Time Frame: Baseline visit (week 0), Week 12 visit
Brief Psychiatric Rating Scale (BPRS) is an 18-item scale that measures positive symptoms, negative symptoms, general psychopathology and affective symptoms. Individual items are scored on a seven point likert scale. The Psychosis subscale comprises 4 items of the BPRS. The total subscale score is the sum of responses and ranges from 4 to 42; a higher score indicates increased severity of symptoms.
Baseline visit (week 0), Week 12 visit
Change in SANS Total Score
Time Frame: Baseline visit (week 0), Week 12 visit
The Scale for Assessment of Negative Symptoms (SANS) will be the instrument for measurement of negative symptoms. SANS is a 19-tiem assessment; each item is rated on a scale from 0-5. The total score is the sum of the 19 individual item ratings and ranges from 0-95; higher scores indicate greater presence of negative symptoms.
Baseline visit (week 0), Week 12 visit
Change in MATRICS Total Score
Time Frame: Baseline visit (week 0), Week 12 visit
Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery is the standard tool for assessing cognitive change in trials of cognitive-enhancing agents in schizophrenia. The assessment comprises ten individual tests to produce; the scores are converted into a standardized overall composite score, with a mean of 50 and a standard deviation of 10; higher scores indicate better cognitive performance.
Baseline visit (week 0), Week 12 visit
Change in Hippocampal Volumetric Integrity
Time Frame: Baseline visit (week 0), Week 12 visit
Assessed via MRI scan.
Baseline visit (week 0), Week 12 visit
Change in Hippocampal Cerebral Blood Flow (CBF)
Time Frame: Baseline visit (week 0), Week 12 visit
CBF measured using arterial spin labeling (ASL).
Baseline visit (week 0), Week 12 visit

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
NYU Langone Health

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Donald Goff, NYU Langone Health

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
August 27, 2020

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
April 1, 2025

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
April 10, 2025

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
March 19, 2020

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 20, 2020

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
March 23, 2020

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
May 29, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 26, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 19-01820

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Individual participant data that underlie the results reported in this article, after deidentification (text, tables, figures, and appendices).

IPD Sharing Time Frame

Beginning 9 months and ending 36 months following article publication or as required by a condition of awards and agreements supporting the research.

IPD Sharing Access Criteria

The investigator who proposed to use the data. Upon reasonable request. Requests should be directed to Donald.goff@nyulangone.org. To gain access, data requestors will need to sign a data access agreement.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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