Reducing Hippocampal Hyperactivity and Improving Cognition in Schizophrenia

Phase 1

Completed

• Conditions: Schizophrenia
• Interventions: Drug: Levetiracetam; Drug: Placebo

• Registration Number: NCT03034356
• Lead Sponsor: VA Office of Research and Development

Brief Summary

This study plans to learn more about the effects of levetiracetam (LEV) on brain activity and cognition in schizophrenia and schizoaffective disorder. Levetiracetam is an anti-seizure drug, also called an anticonvulsant.

Detailed Description

Cognitive symptoms are not currently well-managed in Veterans with schizophrenia, leading to substantially diminished quality of life. Improved treatment strategies clearly are needed. Recent studies suggest taht an overactive hippocampus is associated with cognitive deficits in the illness. Based on findings that the anti-epileptic drug levetiracetam (LEV) reduces hippocampal activity and improves cognition in other clinical populations while being safe and well-tolerated, this study will examine the effects of the drug on hippocampal activity and cognition in Veterans with schizophrenia. In this crossover design, participants will take LEV for 4 weeks and placebo pills for 4 weeks, but will not know the order in which they are taking them.

Study Timeline

• Study First Submitted: 2017-01-25
• Study First Submitted QC: 2017-01-25
• Study First Posted: 2017-01-27
• Study Start: 2018-09-01
• Primary Completion: 2024-06-30
• Study Completion: 2024-06-30
• Status Verified: 2024-08
• Last Update Submitted: 2024-08-19
• Last Update Posted: 2024-08-20

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 67

Inclusion Criteria

• Diagnosis of schizophrenia or schizoaffective disorder
• Good general health
• Normal vital signs (blood pressure, pulse, respiration)

Exclusion Criteria

• Substance abuse

• Significant neurological disorders

• Significant head trauma/injury

• Pregnancy

• MRI-specific exclusion criteria, e.g.,:

  • claustrophobia
  • weight>400 lbs
  • metal in the body

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Levetiracetam, Then Placebo	Placebo	4 weeks of levetiracetam administration (125 mg pill, bid), followed by a 4-week washout, then 4 weeks of placebo pill administration (bid).
Placebo, Then Levetiracetam	Placebo	4 weeks of placebo administration (bid), followed by a 4-week washout, then 4 weeks of levetiracetam administration (125 mg pill, bid).
Levetiracetam, Then Placebo	Levetiracetam	4 weeks of levetiracetam administration (125 mg pill, bid), followed by a 4-week washout, then 4 weeks of placebo pill administration (bid).
Placebo, Then Levetiracetam	Levetiracetam	4 weeks of placebo administration (bid), followed by a 4-week washout, then 4 weeks of levetiracetam administration (125 mg pill, bid).

Primary Outcome Measures

Name	Time	Method
Neurocognitive function	4 weeks	Cognitive function as measured by the Repeatable Battery for the Assessment of Neurological Status (RBANS)

Secondary Outcome Measures

Name	Time	Method
Resting-state neuronal response	4 weeks	Neuronal response (measured via functional magnetic resonance imaging, fMRI) in the hippocampus during rest.

Trial Locations

Locations (1)

Rocky Mountain Regional VA Medical Center, Aurora, CO; 🇺🇸 Aurora, Colorado, United States