Pharmacologic Modulation of Hippocampal Activity in Psychosis

The purpose of this study is to test whether administration of levetiracetam (LEV), a commonly used anti-epileptic that alters neurotransmitter release, can reduce hippocampal hyperactivity. Specifically, we will utilize two functional magnetic resonance imaging (MRI) techniques: 1) blood oxygen level dependence (BOLD) contrast will assess activity with a visual scene processing task that engages the anterior hippocampus and 2) arterial spin labeling (ASL) will assess baseline activity. This study will also assess whether patients have improvement in their symptoms after receiving LEV. Previous studies in people with psychotic disorders have shown that the hippocampus is hyperactive and more activity correlates with worsening of clinical symptoms. Therefore, the aim of this study is to use an intervention to further understand the underlying mechanisms of the hippocampus in psychosis.

Study Overview

• Status: Terminated
• Conditions: Schizophrenia; Psychosis
• Intervention / Treatment: Drug: Levetiracetam 500 mg

• Study Type: Interventional
• Enrollment (Actual): 1
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Tennessee
    • Nashville, Tennessee, United States, 37212
      • Vanderbilt University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion criteria for psychosis subjects:

1. Men and women age 18 - 65.
2. Communicative in English.
3. Provide voluntary, written informed consent.
4. Physically healthy by medical history.
5. BMI > 17.5 and < 45.
6. Diagnosis of a psychotic disorder confirmed by Structured Clinical Interview for DSM-V (SCID) or diagnostic interview with a trained clinician.
7. Stable medication regimen over at least the past two weeks, including the use of either an oral or intramuscular administration of an antipsychotic medication.
8. For females, no longer of child-bearing potential, or agreeing to practice effective contraception during the study; and,
9. For females of child-bearing potential, must have negative urine pregnancy test at time of screening visit and before each testing day.
10. Not breastfeeding/nursing at time of screening or at any time during the study.

Inclusion criteria for healthy controls All of the above except for subjects will be psychiatrically healthy and not taking psychotropic or potentially psychoactive prescription medication.

Exclusion criteria for psychosis subjects

1. Age less than 18 or greater than 65.
2. Not communicative in English.
3. Unable to provide written informed consent.
4. Current medical or neurological illness.
5. History of severe head trauma.
6. BMI < 17.5 or > 45.
7. Meets criteria for diagnosis of substance or alcohol use disorder within the past month.
8. Positive urine pregnancy test at time of screening, before each testing day, or any potential concern for pregnancy at any time during the study.
9. Breastfeeding/nursing at time of screening or at any time during the study.
10. Conditions that preclude MR scanning
11. Conditions that preclude study drug administration

Exclusion criteria for healthy controls

All of the above and in addition:

1. Current use of psychotropic or potentially psychoactive prescription medication.
2. Major psychiatric disorder as determined by DSM-V (major depression, bipolar disorder, obsessive compulsive disorder, post-traumatic stress disorder, etc)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Levetiracetam (LEV) 500 mg; Participants will take their first dose of 500 mg LEV. After a two hour time window, the participants will complete MRI study. After MRI, patients will begin a 2-week intervention with 250 mg BID oral LEV.	Drug: Levetiracetam 500 mg; Levetiracetam (LEV) regulates neuronal synaptic exocytosis and calcium-induced neurotransmitter release and has a therapeutic effect on the excitation-inhibition balance of the hippocampus.; Other Names: Keppra

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hippocampal Activity (Arterial Spin Labeling [ASL] Study)	Change in ASL signal after drug administration	2 hours and 2 weeks after administration
Hippocampal Recruitment (BOLD Study)	Change in BOLD signal after drug administration	2 hours and 2 weeks after administration

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cognitive Symptoms	Change in eye-tracking relational memory task	2 weeks after administration
Positive and Negative Symptoms	Change PANSS score	2 weeks after administration

Collaborators and Investigators

• Sponsor: Vanderbilt University Medical Center

Study record dates

Study Major Dates

• Study Start (ACTUAL): May 11, 2020
• Primary Completion (ACTUAL): August 31, 2020
• Study Completion (ACTUAL): August 31, 2020

Study Registration Dates

• First Submitted: February 18, 2020
• First Submitted That Met QC Criteria: February 18, 2020
• First Posted (ACTUAL): February 20, 2020

Study Record Updates

• Last Update Posted (ACTUAL): August 5, 2021
• Last Update Submitted That Met QC Criteria: July 14, 2021
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Keywords: Hippocampus
• Additional Relevant MeSH Terms: Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia; Psychotic Disorders; Mental Disorders; Anticonvulsants; Nootropic Agents; Levetiracetam
• Other Study ID Numbers: VEPP_200218

Plan for Individual participant data (IPD)

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

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.: No