Effects of Low-dose Levetiracetam on Clinical Symptoms, Cognition and Hippocampal Hyperactivity in Schizophrenia

Not Applicable

Completed

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

• Registration Number: NCT02647437
• Lead Sponsor: University of Colorado, Denver

Brief Summary

Levetiracetam (LEV: (S)-α-ethyl-2-oxo-pyrrolidine acetamide) is an anticonvulsant/antiepileptic drug. The specific aim of this study is to assess the efficacy of low-dose LEV in reducing hippocampal activity in schizophrenia. The investigators also hypothesize that LEV will improve neurocognition in participants with schizophrenia.

Detailed Description

LEV is typically administered in twice-daily doses of 500-1500 mg for the treatment of epilepsy; these doses are generally well tolerated (Patsalos, 2000). Most relevant to the proposed study, LEV (125 mg twice-daily, two week administration) has been shown to reduce hippocampal hyperactivity and improves cognition in patients with mild cognitive impairment (MCI).

The proposed study will administer 125 mg of immediate release LEV twice-daily for two weeks. This dose was chosen to potentially maximize efficacy while minimizing side effects. The proposed dose is substantially lower than the most common dose used clinically for epilepsy treatment of 3000 mg/day.

Study Timeline

• Study Start: 2013-06
• Study First Submitted: 2015-12-29
• Study First Submitted QC: 2016-01-04
• Study First Posted: 2016-01-06
• Primary Completion: 2024-09
• Study Completion: 2024-09
• Status Verified: 2025-04
• Last Update Submitted: 2025-04-21
• Last Update Posted: 2025-04-22

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 18

Inclusion Criteria

• Diagnosis of schizophrenia or schizoaffective disorder
• Good general health
• Normal vital signs (blood pressure, pulse, cardiac, pulmonary, abdominal, neurological exam)
• Normal renal function (as assessed by a metabolic panel at screening if results current within three months are not already available)

Exclusion Criteria

1. Substance abuse
2. Significant neurological disorders
3. Significant head trauma/injury
4. Left-handedness
5. Pregnancy
6. MRI-specific exclusion criteria (e.g., claustrophobia, weight > 450lbs, metal in the body)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Levetiracetam, Then Placebo	Placebo	2 weeks of levetiracetam administration (125 mg pill, bid), followed by a 1-2 week washout, then 2 weeks of placebo pill administration (bid).
Placebo, Then Levetiracetam	Placebo	2 weeks of placebo pill administration (bid), followed by a 1-2 week washout, then 2 weeks of levetiracetam administration (125 mg pill, bid).
Levetiracetam, Then Placebo	Levetiracetam	2 weeks of levetiracetam administration (125 mg pill, bid), followed by a 1-2 week washout, then 2 weeks of placebo pill administration (bid).
Placebo, Then Levetiracetam	Levetiracetam	2 weeks of placebo pill administration (bid), followed by a 1-2 week washout, then 2 weeks of levetiracetam administration (125 mg pill, bid).

Primary Outcome Measures

Name	Time	Method
Resting-state neuronal response	2 weeks	Neuronal response (measured via functional magnetic resonance imaging, fMRI) in the hippocampus during rest

Secondary Outcome Measures

Name	Time	Method
Neurocognitive function	2 weeks	Cognitive function as measured by the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS)

Trial Locations

Locations (2)

University of Colorado Anschutz Medical Campus; 🇺🇸 Aurora, Colorado, United States

University of Colorado Anschutz Medical Campus; 🇺🇸 Aurora, Colorado, United States