CompletedNCT04559529Updated Feb 5, 2024Results posted

Pharmacological Modulation of Hippocampal Activity in Psychosis 2

A Phase 2 interventional study of Levetiracetam (LEV) 500 mg and Placebo in Schizophrenia; Psychosis, sponsored by Vanderbilt University Medical Center. Completed at 1 site in United States. Open to participants aged 18 Years to 65 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2024-02-05.

Sponsored by Vanderbilt University Medical Center · Phase 2, Interventional, and Basic science

Phase: Phase 2
Study type: Interventional
Enrollment: 62
Allocation: Randomized
Ages: 18 Years to 65 Years
Sex: All

Study 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 studied

Schizophrenia; Psychosis

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In context

Schizophrenia

3,470 studies on the registry are indexed under Schizophrenia; 471 are open to participants now.

This study's enrollment of 62 is below the median of 70 across 2,871 interventional studies indexed under Schizophrenia.

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Lead sponsor

Vanderbilt University Medical Center is the lead sponsor of 824 studies on the registry; 164 are open to participants now.

Of its 122 completed or terminated interventional studies of FDA-regulated products, 91 (75%) have results posted.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years to 65 Years
Sexes eligible: All
Accepts healthy volunteers: Yes

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

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

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)

Study design

Phase: Phase 2
Primary purpose: Basic science
Allocation: Randomized
Intervention model: Crossover assignment
Masking: Triple (Participant, Care provider, Investigator)
Enrollment: 62 participants (actual)

Study arms

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 · Drug: Placebo
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 · Drug: Placebo

Interventions

DrugLevetiracetam (LEV) 500 mg
The levetiracetam pill will look just like the placebo pill.
Also known as: Keppra
DrugPlacebo
The placebo pill will look just like the levetiracetam pill, but does not contain any levetiracetam.

What researchers measure

Primary outcomes

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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 2 hours after placebo administration

Results

Posted Feb 5, 2024

Participant flow

First Intervention (1 Day)

Participant flow — First Intervention (1 Day)
Milestone	Healthy Control Participants: Levetiracetam (LEV), Then Placebo	Healthy Control Participants: Placebo, Then Levetiracetam (LEV)	Patients With Schizophrenia: Levetiracetam (LEV), Then Placebo	Patients With Schizophrenia: Placebo, Then Levetiracetam (LEV)
Started	15	15	15	17
Completed	15	15	14	16
Not completed	0	0	1	1
Withdrew: Adverse event	0	0	0	1
Withdrew: Withdrawn due to inability to complete imaging	0	0	1	0

Washout (At Least 7 Days)

Participant flow — Washout (At Least 7 Days)
Milestone	Healthy Control Participants: Levetiracetam (LEV), Then Placebo	Healthy Control Participants: Placebo, Then Levetiracetam (LEV)	Patients With Schizophrenia: Levetiracetam (LEV), Then Placebo	Patients With Schizophrenia: Placebo, Then Levetiracetam (LEV)
Started	15	15	14	16
Completed	15	15	14	16
Not completed	0	0	0	0

Second Intervention (1 Day)

Participant flow — Second Intervention (1 Day)
Milestone	Healthy Control Participants: Levetiracetam (LEV), Then Placebo	Healthy Control Participants: Placebo, Then Levetiracetam (LEV)	Patients With Schizophrenia: Levetiracetam (LEV), Then Placebo	Patients With Schizophrenia: Placebo, Then Levetiracetam (LEV)
Started	15	15	14	16
Completed	15	15	13	16
Not completed	0	0	1	0
Withdrew: Lost to follow-up	0	0	1	0

Outcome measures

PrimaryHippocampal 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.

Time frame:: 2 hours after LEV administration
Reported as:: Mean · ml/100g/min

Hippocampal Activity (Arterial Spin Labeling [ASL] Study) After Levetiracetam (LEV)
ml/100g/min	Healthy Control Participants: Levetiracetam (LEV), Then Placebo	Healthy Control Participants: Placebo, Then Levetiracetam (LEV)	Patients With Schizophrenia: Levetiracetam (LEV), Then Placebo	Patients With Schizophrenia: Placebo, Then Levetiracetam (LEV)
Hippocampal Activity (Arterial Spin Labeling [ASL] Study) After Levetiracetam (LEV)	28.3 (25.2 to 31.3)	27.1 (24.9 to 29.4)	28.0 (24.7 to 31.3)	28.5 (25.5 to 31.5)

PrimaryHippocampal 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.

Time frame:: 2 hours after placebo administration
Reported as:: Mean · ml/100g/min

Hippocampal Activity (Arterial Spin Labeling [ASL] Study) After Placebo
ml/100g/min	Healthy Control Participants: Levetiracetam (LEV), Then Placebo	Healthy Control Participants: Placebo, Then Levetiracetam (LEV)	Patients With Schizophrenia: Levetiracetam (LEV), Then Placebo	Patients With Schizophrenia: Placebo, Then Levetiracetam (LEV)
Hippocampal Activity (Arterial Spin Labeling [ASL] Study) After Placebo	28.1 (25.6 to 30.5)	28.3 (25.2 to 31.4)	28.1 (25.5 to 30.7)	28.7 (25.5 to 32.0)

PrimaryHippocampal 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.

Time frame:: 2 hours after LEV administration
Reported as:: Mean · BOLD percent signal change

Hippocampal Recruitment (Blood-Oxygen-Level-Dependent [BOLD] Study) After Levetiracetam (LEV)
BOLD percent signal change	Healthy Control Participants: Levetiracetam (LEV), Then Placebo	Healthy Control Participants: Placebo, Then Levetiracetam (LEV)	Patients With Schizophrenia: Levetiracetam (LEV), Then Placebo	Patients With Schizophrenia: Placebo, Then Levetiracetam (LEV)
Hippocampal Recruitment (Blood-Oxygen-Level-Dependent [BOLD] Study) After Levetiracetam (LEV)	-0.0342 (-0.2172 to 0.1489)	0.1216 (-0.0382 to 0.2813)	0.2915 (0.1084 to 0.4745)	0.2381 (-0.0078 to 0.4840)

PrimaryHippocampal 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.

Time frame:: 2 hours after placebo administration
Reported as:: Mean · BOLD percent signal change

Hippocampal Recruitment (Blood-Oxygen-Level-Dependent [BOLD] Study) After Placebo
BOLD percent signal change	Healthy Control Participants: Levetiracetam (LEV), Then Placebo	Healthy Control Participants: Placebo, Then Levetiracetam (LEV)	Patients With Schizophrenia: Levetiracetam (LEV), Then Placebo	Patients With Schizophrenia: Placebo, Then Levetiracetam (LEV)
Hippocampal Recruitment (Blood-Oxygen-Level-Dependent [BOLD] Study) After Placebo	0.1908 (-0.0158 to 0.3975)	0.0507 (-0.1081 to 0.2094)	0.1769 (-0.0607 to 0.4146)	0.0703 (-0.1121 to 0.2526)

Adverse events

Collected over Up to 4 hours after levetiracetam or placebo administration.. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Healthy Control Participants: Levetiracetam (LEV)	0/30 (0%)	0/30 (0%)	0/30 (0%)
Healthy Control Participants: Placebo	0/30 (0%)	0/30 (0%)	0/30 (0%)
Patients With Schizophrenia: Levetiracetam (LEV)	0/31 (0%)	0/31 (0%)	0/31 (0%)
Patients With Schizophrenia: Placebo	0/30 (0%)	0/30 (0%)	1/30 (3.3%)

Most frequent other events

Most frequent other events
Event	Healthy Control Participants: Levetiracetam (LEV)	Healthy Control Participants: Placebo	Patients With Schizophrenia: Levetiracetam (LEV)	Patients With Schizophrenia: Placebo
VomitingGastrointestinal disorders	0/30	0/30	0/31	1/30

Baseline characteristics

Age, Continuous
Age, Continuous(years)	Healthy Control Participants: Levetiracetam (LEV), Then Placebo	Healthy Control Participants: Placebo, Then Levetiracetam (LEV)	Patients With Schizophrenia: Levetiracetam (LEV), Then Placebo	Patients With Schizophrenia: Placebo, Then Levetiracetam (LEV)	Total
Mean	32.2 ± 9.0	36.0 ± 11.2	35.7 ± 12.1	34.8 ± 12.7	34.7 ± 11.2

Sex: Female, Male
Sex: Female, Male(Participants)	Healthy Control Participants: Levetiracetam (LEV), Then Placebo	Healthy Control Participants: Placebo, Then Levetiracetam (LEV)	Patients With Schizophrenia: Levetiracetam (LEV), Then Placebo	Patients With Schizophrenia: Placebo, Then Levetiracetam (LEV)	Total
Female	5	4	5	4	18
Male	10	11	9	12	42

Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)	Healthy Control Participants: Levetiracetam (LEV), Then Placebo	Healthy Control Participants: Placebo, Then Levetiracetam (LEV)	Patients With Schizophrenia: Levetiracetam (LEV), Then Placebo	Patients With Schizophrenia: Placebo, Then Levetiracetam (LEV)	Total
Hispanic or Latino	3	0	0	1	4
Not Hispanic or Latino	12	15	14	15	56
Unknown or Not Reported	0	0	0	0	0

Race (NIH/OMB)
Race (NIH/OMB)(Participants)	Healthy Control Participants: Levetiracetam (LEV), Then Placebo	Healthy Control Participants: Placebo, Then Levetiracetam (LEV)	Patients With Schizophrenia: Levetiracetam (LEV), Then Placebo	Patients With Schizophrenia: Placebo, Then Levetiracetam (LEV)	Total
American Indian or Alaska Native	0	0	0	0	0
Asian	0	1	0	0	1
Native Hawaiian or Other Pacific Islander	0	0	0	0	0
Black or African American	3	4	0	6	13
White	12	8	14	10	44
More than one race	0	2	0	0	2
Unknown or Not Reported	0	0	0	0	0

Region of Enrollment
Region of Enrollment(participants)	Healthy Control Participants: Levetiracetam (LEV), Then Placebo	Healthy Control Participants: Placebo, Then Levetiracetam (LEV)	Patients With Schizophrenia: Levetiracetam (LEV), Then Placebo	Patients With Schizophrenia: Placebo, Then Levetiracetam (LEV)	Total
United States	15	15	14	16	60

Study locations

1 site

Vanderbilt University Medical Center
Nashville, Tennessee 37212, United States

References and documents

Study documents

Protocol and statistical analysis plan · Apr 15, 2021

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Feb 5, 2024, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT04559529
Lead sponsor: Vanderbilt University Medical Center
Responsible party: Stephan Heckers (Dept Chairperson Professor, Vanderbilt University Medical Center) — Principal investigator
First posted: Sep 23, 2020
Start date: Sep 23, 2020
Primary completion: Dec 31, 2023
Completion: Dec 31, 2023
Results posted: Feb 5, 2024
Last update: Feb 5, 2024

Study contacts

Stephan Heckers, MD

principal investigator · Vanderbilt University Medical Center

Oversight

Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No

View the source record on ClinicalTrials.gov ↗

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