Pharmacological Modulation of Hippocampal Activity in Psychosis 2

NCT04559529 | Completed Phase 2 Results FDA Drug

• 1 other identifier: VEPP_200915
• Study Type: interventional
• Target: 62
• 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 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.

Conditions

Schizophrenia; Psychosis

Outcome Measures

Primary Outcomes (4)

• 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

Study Arms (2)

Levetiracetam (LEV), then Placebo

EXPERIMENTAL

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; Drug: Placebo

Placebo, then Levetiracetam (LEV)

EXPERIMENTAL

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; Drug: Placebo

Interventions

Levetiracetam (LEV) 500 mg DRUG

The levetiracetam pill will look just like the placebo pill.

Also known as: Keppra

Levetiracetam (LEV), then Placebo; Placebo, then Levetiracetam (LEV)

Placebo DRUG

The placebo pill will look just like the levetiracetam pill, but does not contain any levetiracetam.

Levetiracetam (LEV), then Placebo; Placebo, then Levetiracetam (LEV)

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 Diagnostic and Statistical Manual-5 (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 (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,
• For females of child-bearing potential, must have a negative urine pregnancy test before MRI and drug administration.
• Not breastfeeding/nursing at time of screening or at any time during the study.
• \. All of the above except for subjects will be psychiatrically healthy and not taking psychotropic or potentially psychoactive prescription medication.
• \----

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 during the study.
• Breastfeeding/nursing at time of screening or at any time during the study.
• Conditions that preclude MR scanning (as defined in the Screening Form)
• Conditions that preclude study drug administration (as defined in the Screening Form)
• All of the above and in addition:
• Current use of psychotropic or potentially psychoactive prescription medication.
• Major psychiatric disorder as determined by Diagnostic and Statistical Manual -5 (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; Levamisole

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; Thiazoles; Sulfur Compounds; Imidazoles; Azoles

Results Point of Contact

• Title: Stephan Heckers, MD; Principal Investigator
• Organization: Vanderbilt University Medical Center

stephan.heckers@vumc.org

6153222665

Study Officials

• Stephan Heckers, MD

  Vanderbilt University Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: During Visit 2, participants will be randomly assigned to an intervention arm in which they will receive two 250mg LEV capsules or two placebo capsules. Both the participant and the research team will be blinded to which arm each participant is in. During Visit 3, the participant will undergo cross-over and receive either two 250mg LEV capsules or two placebo capsules (whichever intervention they did not receive in Visit 2).
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Dept Chairperson Professor

Model Details: 2-way crossover, double-blind, randomized controlled study

Study Record Dates

• First Submitted: September 16, 2020
• First Posted: September 23, 2020
• Study Start: September 23, 2020
• Primary Completion: December 31, 2023
• Study Completion: December 31, 2023
• Last Updated: February 5, 2024
• Results First Posted: February 5, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)