Reducing Hippocampal Hyperactivity and Improving Cognition in Schizophrenia

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Schizophrenia
• Intervention / Treatment: Drug: Placebo; Drug: Levetiracetam

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 Type: Interventional
• Enrollment (Actual): 67
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Jason R Tregellas, PhD; Phone Number: (303) 315-1086; Email: Jason.Tregellas@va.gov

Study Locations

• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Rocky Mountain Regional VA Medical Center, Aurora, CO

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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 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; 4 weeks of levetiracetam administration (125 mg pill, bid), followed by a 4-week washout, then 4 weeks of placebo pill administration (bid).	Drug: Placebo; Placebo; Drug: Levetiracetam; Anticonvulsant drug; Other Names: Keppra
Experimental: Placebo, Then Levetiracetam; 4 weeks of placebo administration (bid), followed by a 4-week washout, then 4 weeks of levetiracetam administration (125 mg pill, bid).	Drug: Placebo; Placebo; Drug: Levetiracetam; Anticonvulsant drug; Other Names: Keppra

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Neurocognitive function	Cognitive function as measured by the Repeatable Battery for the Assessment of Neurological Status (RBANS)	4 weeks

Secondary 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.	4 weeks

Collaborators and Investigators

• Sponsor: VA Office of Research and Development
• Investigators: Principal Investigator: Jason R. Tregellas, PhD, Rocky Mountain Regional VA Medical Center, Aurora, CO

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2018
• Primary Completion (Estimated): June 30, 2024
• Study Completion (Estimated): June 30, 2024

Study Registration Dates

• First Submitted: January 25, 2017
• First Submitted That Met QC Criteria: January 25, 2017
• First Posted (Estimated): January 27, 2017

Study Record Updates

• Last Update Posted (Actual): October 23, 2023
• Last Update Submitted That Met QC Criteria: October 19, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: Schizophrenia
• Additional Relevant MeSH Terms: Mental Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia; Anticonvulsants; Nootropic Agents; Levetiracetam
• Other Study ID Numbers: MHBB-006-16S; I01CX001414 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: A de-identified, anonymized dataset will be created and shared.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes