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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Schizophrenia
• Intervention / Treatment: Drug: Placebo; Drug: Levetiracetam

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 Type: Interventional
• Enrollment (Estimated): 30
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Kristina T Legget, Ph.D.; Phone Number: 303-724-5809; Email: kristina.legget@ucdenver.edu

Study Locations

• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Recruiting
      • University of Colorado Anschutz Medical Campus
      • Contact: Kristina T Legget, Ph.D.; Phone Number: 303-724-5809; Email: kristina.legget@ucdenver.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 63 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Levetiracetam, Then 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).	Drug: Placebo; Drug: Levetiracetam; Other Names: Keppra
Experimental: Placebo, Then 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).	Drug: Placebo; Drug: Levetiracetam; Other Names: Keppra

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Neurocognitive function	Cognitive function as measured by the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS)	2 weeks

Collaborators and Investigators

• Sponsor: University of Colorado, Denver
• Investigators: Principal Investigator: Jason Tregellas, Ph.D., University of Colorado, Denver

Study record dates

Study Major Dates

• Study Start: June 1, 2013
• Primary Completion (Estimated): June 1, 2024
• Study Completion (Estimated): June 1, 2024

Study Registration Dates

• First Submitted: December 29, 2015
• First Submitted That Met QC Criteria: January 4, 2016
• First Posted (Estimated): January 6, 2016

Study Record Updates

• Last Update Posted (Estimated): February 5, 2024
• Last Update Submitted That Met QC Criteria: February 2, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia; Anticonvulsants; Nootropic Agents; Levetiracetam
• Other Study ID Numbers: 13-1495; UL1TR001082 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO