Levetiracetam in Early Psychosis

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

In order to establish target engagement and identify an effective dose the investigators will conduct a placebo-controlled single-dose parallel group trial of levetiracetam 185 mg and 500 mg in 24 medication-naïve early psychosis (EP) patients, measuring hippocampal activity by pulsed arterial spin labelling (ASL) pre-dose and 2 hours post-dose. The lower dose is calculated to achieve blood levels within the range that were associated with reduced hippocampal activity and improved cognition in patients with mild cognitive impairment; the higher dose is a typical antiepileptic dose. Successful demonstration of target engagement will be defined by an effect size of 0.5 or greater compared to placebo in reduction by levetiracetam of hippocampal blood flow measured by ASL. The optimal dose will be defined by maximal reduction of hippocampal perfusion in the absence of clinically-significant adverse effects. The investigators will also study 8 healthy control subjects to verify that baseline hippocampal blood flow is elevated in the sample of EP subjects.

Study Overview

• Status: Completed
• Conditions: Schizophrenia; Psychosis; Schizo Affective Disorder; Schizophreniform
• Intervention / Treatment: Drug: Levetiracetam; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 48
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10016
      • New York University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 33 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Males and females 16 to 35 years of age, inclusive, at time of informed consent
2. Must have experienced a first episode of non-affective psychosis within 5 years and exhibit current psychosis, as defined by a score of ≥ 2 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
3. Must have a diagnosis of either schizophrenia, schizoaffective disorder or schizophreniform disorder as established by a Structured Clinical Interview for DSMIV TR (SCID)
4. Must not have taken an oral antipsychotic medication within the past 4 weeks prior to study enrollment or received a long acting injectable antipsychotic within 3 times the dosing interval

5. If female and of childbearing potential, patients must:

   1. Have a negative urine pregnancy test (all females regardless of childbearing potential will be required to submit a pregnancy test)
   2. Not be nursing or planning a pregnancy for the duration of the study through 30 days after the last dosing visit
   3. 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:

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

   1. A positive urine toxic screen (excluding THC, tricyclic antidepressants, or benzodiazepines (if prescribed))
   2. Moderate or severe cannabis use disorder
   3. Use of marijuana within the 72 hours prior to MRI scanning by self report
2. Diagnosis of major mood disorder or other Axis I disorder other than Schizophrenia, Schizoaffective Disorder or Schizophreniform Disorder
3. 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 and/or PhD or MD level clinician completing screening visit
4. Pregnant, nursing or positive urine pregnancy test
5. 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
6. Metal implants, pacemaker, or other metal in the body or medicinal patch
7. History of claustrophobia
8. Currently taking any antipsychotic medication (within 4 weeks)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Levetiracetam 185 mg; A single dose of 185mg of levetiracetam administered orally to participants. Participants undergo a 15-minute MRI scan using arterial spin labeling (ASL) before dosing and two hours post-dosing.	Drug: Levetiracetam; Levetiracetam is an atypical anticonvulsant that is frequently used in children and adults due to its superior tolerability, ease of use and excellent safety profile.; Other Names: Keppra
Experimental: Levetiracetam 500mg; A single dose of 500mg of levetiracetam administered orally to participants. Participants undergo a 15-minute MRI scan using arterial spin labeling (ASL) before dosing and two hours post-dosing.	Drug: Levetiracetam; Levetiracetam is an atypical anticonvulsant that is frequently used in children and adults due to its superior tolerability, ease of use and excellent safety profile.; Other Names: Keppra
Placebo Comparator: Placebo; A single dose of placebo administered orally to participants. Participants undergo a 15-minute MRI scan using arterial spin labeling (ASL) before dosing and two hours post-dosing.	Drug: Placebo; Prepared in capsules to appear identical to levetiracetam.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Cerebral Blood Flow (CBF)	CBF will be measured by Arterial Spin Labeling (ASL)	Baseline, 2 Hours Post-Treatment

Collaborators and Investigators

• Sponsor: NYU Langone Health
• Collaborators: National Institutes of Health (NIH)
• Investigators: Principal Investigator: Donald Goff, MD, NYU Langone Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): August 18, 2017
• Primary Completion (Actual): November 3, 2021
• Study Completion (Actual): November 3, 2021

Study Registration Dates

• First Submitted: April 17, 2017
• First Submitted That Met QC Criteria: April 21, 2017
• First Posted (Actual): April 26, 2017

Study Record Updates

• Last Update Posted (Actual): November 21, 2022
• Last Update Submitted That Met QC Criteria: October 26, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Keywords: Levetiracetam; Early Psychosis
• Additional Relevant MeSH Terms: Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia; Psychotic Disorders; Mental Disorders; Mood Disorders; Anticonvulsants; Nootropic Agents; Levetiracetam
• Other Study ID Numbers: 17-00266

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: The de-identified participant data from the final research dataset used in the published manuscript will be shared upon reasonable request beginning 9 months and ending 36 months following article publication or as required by a condition of awards and agreements supporting the research provided the investigator who proposes to use the data executes a data use agreement with NYU Langone Health. Requests may be directed to: donald.goff@nyulangone.org. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.
• 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 will have access to 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; Statistical Analysis Plan (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
• product manufactured in and exported from the U.S.: Yes