Pharmacologic Modulation of Hippocampal Activity in Psychosis

NCT04277936 | Terminated Phase 2 Results FDA Drug

• 1 other identifier: VEPP_200218
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Schizophrenia; Psychosis

Keywords

Hippocampus

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (2)

• Cognitive Symptoms

  2 weeks after administration

• Positive and Negative Symptoms

  2 weeks after administration

Study Arms (1)

Levetiracetam (LEV) 500 mg

EXPERIMENTAL

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

Interventions

Levetiracetam 500 mg DRUG

Levetiracetam (LEV) regulates neuronal synaptic exocytosis and calcium-induced neurotransmitter release and has a therapeutic effect on the excitation-inhibition balance of the hippocampus.

Also known as: Keppra

Levetiracetam (LEV) 500 mg

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• Age less than 18 or greater than 65.
• Not communicative in English.
• Unable to provide written informed consent.
• Current medical or neurological illness.
• History of severe head trauma.
• BMI \< 17.5 or \> 45.
• Meets criteria for diagnosis of substance or alcohol use disorder within the past month.
• Positive urine pregnancy test at time of screening, before each testing day, or any potential concern for pregnancy at any time during the study.
• Breastfeeding/nursing at time of screening or at any time during the study.
• Conditions that preclude MR scanning
• Conditions that preclude study drug administration
• All of the above and in addition:
• Current use of psychotropic or potentially psychoactive prescription medication.
• Major psychiatric disorder as determined by DSM-V (major depression, bipolar disorder, obsessive compulsive disorder, post-traumatic stress disorder, etc)

Sponsors & Collaborators

• Vanderbilt University Medical Center: lead

Study Sites (1)

Vanderbilt University Medical Center

Nashville, Tennessee, 37212, United States

Location

MeSH Terms

Conditions

Schizophrenia; Psychotic Disorders

Interventions

Levetiracetam

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Acetamides; Amides; Organic Chemicals; Acetates; Acids, Acyclic; Carboxylic Acids; Pyrrolidinones; Pyrrolidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Stephan Heckers
• Organization: Vanderbilt University Medical Center

stephan.heckers@vumc.org

6159222665

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Department Chair

Study Record Dates

• First Submitted: February 18, 2020
• First Posted: February 20, 2020
• Study Start: May 11, 2020
• Primary Completion: August 31, 2020
• Study Completion: August 31, 2020
• Last Updated: August 5, 2021
• Results First Posted: August 5, 2021

Record last verified: 2021-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)