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Trial record 2 of 2 for:    Levetiracetam in Early Psychosis

R33: Levetiracetam in Early Psychosis

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ClinicalTrials.gov Identifier: NCT04317807
Recruitment Status : Recruiting
First Posted : March 23, 2020
Last Update Posted : October 31, 2022
Sponsor:
Information provided by (Responsible Party):
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). .

Condition or disease Intervention/treatment Phase
Early Psychosis Drug: Levetiracetam Pill Other: Placebo Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 84 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Care Provider)
Primary Purpose: Treatment
Official Title: A 12-week Randomized, Double-blind, Placebo-controlled Trial Investigating the Effects of Levetiracetam in Early Psychosis
Actual Study Start Date : August 1, 2020
Estimated Primary Completion Date : January 2023
Estimated Study Completion Date : January 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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 Name: 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.




Primary Outcome Measures :
  1. The symptoms measured by the BPRS total score [ Time Frame: 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 :
  1. Compared to placebo, levetiracetam will improve psychotic symptoms measured by the BPRS psychosis subscale. [ 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 24-item scale that measures positive symptoms, negative symptoms, general psychopathology and affective symptoms. Individual items are scored on a seven point likert scale.

  2. Compared to placebo, levetiracetam will be associated with less hippocampal volume loss over 12 weeks. [ Time Frame: 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).

  3. Compare to placebo, levetiracetam will improve negative symptoms measured by the modified SANS total score. [ Time Frame: 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.

  4. Compared to placebo, levetiracetam will improve cognitive functioning measured by the MATRICS composite score. [ Time Frame: 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.



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Ages Eligible for Study:   16 Years to 40 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04317807


Contacts
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Contact: Gillian Capichioni 917-628-0552 gillian.capichioni@nyulangone.org
Contact: Fumika Ando 917-628-0552 fumika.ando@nyulangone.org

Locations
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United States, New York
NYU Langone Health Recruiting
New York, New York, United States, 10016
Contact: Gillian Capichioni, BS    917-628-0552    gillian.capichioni@nyulangone.org   
Contact: Fumika Ando    917-628-0552    fumika.ando@nyulangone.org   
Principal Investigator: Donald Goff, MD         
Sponsors and Collaborators
NYU Langone Health
Investigators
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Principal Investigator: Donald Goff NYU Langone Health
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Responsible Party: NYU Langone Health
ClinicalTrials.gov Identifier: NCT04317807    
Other Study ID Numbers: 19-01820
First Posted: March 23, 2020    Key Record Dates
Last Update Posted: October 31, 2022
Last Verified: May 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Individual participant data that underlie the results reported in this article, after deidentification (text, tables, figures, and appendices).
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
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.
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.

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Psychotic Disorders
Mental Disorders
Schizophrenia Spectrum and Other Psychotic Disorders
Levetiracetam
Anticonvulsants
Nootropic Agents