R33: Levetiracetam in Early Psychosis

Phase 2

Recruiting

• Conditions: Early Psychosis
• Interventions: Drug: Levetiracetam Pill; Other: Placebo

• Registration Number: NCT04317807
• Lead Sponsor: NYU Langone Health

Brief 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. 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). .

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.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2020-03-19
• Study First Submitted QC: 2020-03-20
• Study First Posted: 2020-03-23
• Study Start: 2020-08-27
• Status Verified: 2024-01
• Last Update Submitted: 2024-01-02
• Last Update Posted: 2024-01-03
• Primary Completion: 2025-01
• Study Completion: 2025-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 84

Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Study Drug group	Levetiracetam Pill	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.
Placebo Group	Placebo	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.

Primary Outcome Measures

Name	Time	Method
The symptoms measured by the BPRS total score	up to week 12	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 24-item scale that measures positive symptoms, negative symptoms, general psychopathology and affective symptoms. Individual items are scored on a seven point likert scale. A higher score on the BPRS items indicate increased severity.

Secondary Outcome Measures

Name	Time	Method
Compared to placebo, levetiracetam will improve psychotic symptoms measured by the BPRS psychosis subscale.	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 24-item scale that measures positive symptoms, negative symptoms, general psychopathology and affective symptoms. Individual items are scored on a seven point likert scale.
Compared to placebo, levetiracetam will be associated with less hippocampal volume loss over 12 weeks.	Baseline visit (week 0), Week 12 visit	Hippocampal volume loss will be measured by assessing change in cerebral blood flow (CBF) as measured by Arterial Spin Labeling (ASL).
Compare to placebo, levetiracetam will improve negative symptoms measured by the modified SANS total score.	Baseline visit (week 0), Week 12 visit	Scale for Assessment of Negative Symptoms (SANS) will be the instrument for measurement of negative symptoms. Factor analysis has revealed good construct validity for all items of the SANS scale except the Attention subscale which clusters with measures of cognitive impairment rather than negative symptoms. Two, three and five domain models have been proposed based on factor analysis; this research will use the total score (minus the Attention Subscale) and the two factor solution (avolition and affective expression) to measure negative symptoms.
Compared to placebo, levetiracetam will improve cognitive functioning measured by the MATRICS composite score.	Baseline visit (week 0), Week 6 visit, 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. It will be administered at baseline, week 6 and at week 12 to measure whether cognitive function has increased.

Trial Locations

Locations (1)

NYU Langone Health; 🇺🇸 New York, New York, United States