Pharmacological Modulation of Hippocampal Activity in Psychosis 2

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 in people with psychotic disorders. Specifically, the investigators will utilize two functional magnetic resonance imaging (MRI) techniques: 1) blood-oxygen-level-dependent (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. 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: Completed
• Conditions: Schizophrenia; Psychosis
• Intervention / Treatment: Drug: Levetiracetam (LEV) 500 mg; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 62
• 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

Description

Inclusion Criteria:

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 Diagnostic and Statistical Manual-5 (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 (e.g., established use of oral, injected or implanted hormonal methods of contraception; placement of an intrauterine device or intrauterine system; barrier methods: condom with spermicidal foam/gel/film/cream/suppository or occlusive cap [diaphragm or cervical/vault caps] with spermicidal foam/gel/film/cream/suppository; male partner sterilization; or true abstinence when this is in line with the preferred and usual lifestyle of the subject); and,
9. For females of child-bearing potential, must have a negative urine pregnancy test before MRI and drug administration.
10. Not breastfeeding/nursing at time of screening or at any time during the study.

Inclusion criteria for healthy controls

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

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Exclusion Criteria:

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 during the study.
9. Breastfeeding/nursing at time of screening or at any time during the study.
10. Conditions that preclude MR scanning (as defined in the Screening Form)
11. Conditions that preclude study drug administration (as defined in the Screening Form)

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 Diagnostic and Statistical Manual -5 (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: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Levetiracetam (LEV), then Placebo; Participants will first receive two 250mg LEV capsules on the same day. After one week, they will receive two placebo capsules on the same day.	Drug: Levetiracetam (LEV) 500 mg; The levetiracetam pill will look just like the placebo pill.; Other Names: Keppra; Drug: Placebo; The placebo pill will look just like the levetiracetam pill, but does not contain any levetiracetam.
Experimental: Placebo, then Levetiracetam (LEV); Participants will first receive two placebo capsules on the same day. After one week, they will receive two 250mg LEV capsules on the same day.	Drug: Levetiracetam (LEV) 500 mg; The levetiracetam pill will look just like the placebo pill.; Other Names: Keppra; Drug: Placebo; The placebo pill will look just like the levetiracetam pill, but does not contain any levetiracetam.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hippocampal Activity (Arterial Spin Labeling [ASL] Study) After Levetiracetam (LEV)	ASL signal after LEV, using Magnetic Resonance Imaging (MRI) scanning of the brain. ASL measures cerebral blood flow, which is linked to neuronal metabolism and functions as a proxy for neuronal activity.	2 hours after LEV administration
Hippocampal Activity (Arterial Spin Labeling [ASL] Study) After Placebo	ASL signal after placebo, using Magnetic Resonance Imaging (MRI) scanning of the brain. ASL measures cerebral blood flow, which is linked to neuronal metabolism and functions as a proxy for neuronal activity.	2 hours after placebo administration
Hippocampal Recruitment (Blood-Oxygen-Level-Dependent [BOLD] Study) After Levetiracetam (LEV)	BOLD signal after LEV, using Magnetic Resonance Imaging (MRI) scanning of the brain. This method reflects changes in oxygenation of blood in the brain during a scene-processing task that engages, or recruits, the hippocampus.	2 hours after LEV administration
Hippocampal Recruitment (Blood-Oxygen-Level-Dependent [BOLD] Study) After Placebo	BOLD signal after placebo, using Magnetic Resonance Imaging (MRI) scanning of the brain. This method reflects changes in oxygenation of blood in the brain during a scene-processing task that engages, or recruits, the hippocampus.	2 hours after placebo administration

Collaborators and Investigators

• Sponsor: Vanderbilt University Medical Center
• Investigators: Principal Investigator: Stephan Heckers, MD, Vanderbilt University Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): September 23, 2020
• Primary Completion (Actual): December 31, 2023
• Study Completion (Actual): December 31, 2023

Study Registration Dates

• First Submitted: September 16, 2020
• First Submitted That Met QC Criteria: September 16, 2020
• First Posted (Actual): September 23, 2020

Study Record Updates

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

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia; Psychotic Disorders; Mental Disorders; Anticonvulsants; Nootropic Agents; Levetiracetam
• Other Study ID Numbers: VEPP_200915

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.: Yes