Clinical trial NCT04317807: R33: Levetiracetam in Early Psychosis
Official title: A 12-week Randomized, Double-blind, Placebo-controlled Trial Investigating the Effects of Levetiracetam in Early Psychosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Early Psychosis
Lead sponsor: NYU Langone Health
Sponsor class: OTHER
First posted: 2020-03-23
Enrollment: 65
Sex: ALL
Minimum age (years): 16
Maximum age (years): 40
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: The symptoms measured by the BPRS total score
timeFrame: up to week 12
Secondary outcomes:
measure: Compared to placebo, levetiracetam will improve psychotic symptoms measured by the BPRS psychosis subscale.
timeFrame: Baseline visit (week 0), Week 12 visit
measure: Compared to placebo, levetiracetam will be associated with less hippocampal volume loss over 12 weeks.
timeFrame: Baseline visit (week 0), Week 12 visit
measure: Compare to placebo, levetiracetam will improve negative symptoms measured by the modified SANS total score.
timeFrame: Baseline visit (week 0), Week 12 visit
measure: Compared to placebo, levetiracetam will improve cognitive functioning measured by the MATRICS composite score.
timeFrame: Baseline visit (week 0), Week 6 visit, Week 12 visit
Other outcomes:
Locations:
city: New York
country: United States
facility: NYU Langone Health
state: New York
Study officials:
affiliation: NYU Langone Health
name: Donald Goff
role: PRINCIPAL_INVESTIGATOR
References: