Early PsychosisPhase 2NCT04317807
R33: Levetiracetam in Early Psychosis
A Phase 2 study testing Levetiracetam Pill in people with Early Psychosis, run by NYU Langone Health at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 16 to 40 years
- Conditions the study is for
- Early Psychosis
- What is being tested?
- Levetiracetam Pill
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 65 participants
- Where
- 1 siteUnited States
- Study dates
- 27 Aug 2020to 10 Apr 2025
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 16 to 40 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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). .
Read the 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.
- Conditions
- Early Psychosis
- Being tested
- Levetiracetam Pill, Placebo
- Medical subject headings
- Psychotic Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Levetiracetam PillDrug
Also called Keppra
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.
PlaceboOther
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.
| Study group | Role | What they receive |
|---|---|---|
| Study Drug group | Active comparator | 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. Receives: Drug: Levetiracetam Pill |
| Placebo Group | Placebo comparator | 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. Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in BPRS total score
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.
Measured: Baseline visit (week 0), Week 12 visit
Secondary outcomes (5)
Change in BPRS Psychosis Subscale
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.
Measured: Baseline visit (week 0), Week 12 visit
Change in SANS Total Score
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.
Measured: Baseline visit (week 0), Week 12 visit
Change in MATRICS Total Score
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.
Measured: Baseline visit (week 0), Week 12 visit
Change in Hippocampal Volumetric Integrity
Assessed via MRI scan.
Measured: Baseline visit (week 0), Week 12 visit
Change in Hippocampal Cerebral Blood Flow (CBF)
CBF measured using arterial spin labeling (ASL).
Measured: Baseline visit (week 0), Week 12 visit
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Mar 2020
- Study start27 Aug 2020
- Primary completion1 Apr 2025
- Study completion10 Apr 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Early PsychosisStudies of the same condition, open and under way.
- More trials run by NYU Langone HealthThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Care provider
- Enrolment
- 65 participants (actual)
Sponsor and investigators
- Lead sponsor
- NYU Langone Health
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Donald Goff, Principal investigator, NYU Langone Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04317807
- Sponsor's protocol ID
- 19-01820
- Status last verified
- May 2026
- First submitted
- 19 Mar 2020
- Last updated
- 29 May 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Individual participant data that underlie the results reported in this article, after deidentification (text, tables, figures, and appendices).