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Pharmacological Modulation of Hippocampal Activity in Psychosis 2

Primary Purpose

Schizophrenia; Psychosis

Status
Active
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Levetiracetam (LEV) 500 mg
Placebo
Sponsored by
Vanderbilt University Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Schizophrenia; Psychosis

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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.

----

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)

Sites / Locations

  • Vanderbilt University Medical Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Levetiracetam (LEV), then Placebo

Placebo, then Levetiracetam (LEV)

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

Hippocampal activity (Arterial Spin Labeling [ASL] study)
Change in ASL signal after intervention, using Magnetic Resonance Imaging (MRI) scanning of the brain
Hippocampal recruitment (Blood-Oxygen-Level-Dependent [BOLD] study)
Change in BOLD signal after intervention, using Magnetic Resonance Imaging (MRI) scanning of the brain

Secondary Outcome Measures

Full Information

First Posted
September 16, 2020
Last Updated
February 12, 2023
Sponsor
Vanderbilt University Medical Center
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1. Study Identification

Unique Protocol Identification Number
NCT04559529
Brief Title
Pharmacological Modulation of Hippocampal Activity in Psychosis 2
Official Title
Pharmacological Modulation of Hippocampal Activity in Psychosis 2
Study Type
Interventional

2. Study Status

Record Verification Date
February 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
September 23, 2020 (Actual)
Primary Completion Date
September 20, 2025 (Anticipated)
Study Completion Date
September 20, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Vanderbilt University Medical Center

4. Oversight

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
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Schizophrenia; Psychosis

7. Study Design

Primary Purpose
Basic Science
Study Phase
Phase 2
Interventional Study Model
Crossover Assignment
Model Description
2-way crossover, double-blind, randomized controlled study
Masking
ParticipantCare ProviderInvestigator
Masking Description
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).
Allocation
Randomized
Enrollment
62 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Levetiracetam (LEV), then Placebo
Arm Type
Experimental
Arm Description
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.
Arm Title
Placebo, then Levetiracetam (LEV)
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Levetiracetam (LEV) 500 mg
Other Intervention Name(s)
Keppra
Intervention Description
The levetiracetam pill will look just like the placebo pill.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
The placebo pill will look just like the levetiracetam pill, but does not contain any levetiracetam.
Primary Outcome Measure Information:
Title
Hippocampal activity (Arterial Spin Labeling [ASL] study)
Description
Change in ASL signal after intervention, using Magnetic Resonance Imaging (MRI) scanning of the brain
Time Frame
2 hours after administration
Title
Hippocampal recruitment (Blood-Oxygen-Level-Dependent [BOLD] study)
Description
Change in BOLD signal after intervention, using Magnetic Resonance Imaging (MRI) scanning of the brain
Time Frame
2 hours after administration

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Inclusion criteria for psychosis subjects 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. 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. ---- Exclusion Criteria: Exclusion criteria for psychosis subjects 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) Exclusion criteria for healthy controls 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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Stephan Heckers, MD
Organizational Affiliation
Vanderbilt University Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Vanderbilt University Medical Center
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37212
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

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Pharmacological Modulation of Hippocampal Activity in Psychosis 2

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