Schizophrenia; PsychosisPhase 2NCT04559529

Pharmacological Modulation of Hippocampal Activity in Psychosis 2

A Phase 2 study testing Levetiracetam (LEV) 500 mg in people with Schizophrenia; Psychosis, run by Vanderbilt University Medical Center at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial summary

Who is it for?: Ages 18 to 65 yearsHealthy volunteers can take part
Conditions the study is for: Schizophrenia; Psychosis
What is being tested?: Levetiracetam (LEV) 500 mg
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 62 participants
Where: 1 siteUnited States
Study dates: 23 Sep 2020to 31 Dec 2023
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 65 years
All sexes
Healthy volunteers accepted
Adult, Older adult

Who may be able to join

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.

Show all 12Show fewer

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

Who cannot join

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.

Show all 14Show fewer

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)

Trial locations and contacts

1 site in 1 country.

United States1 site

Vanderbilt University Medical Center
Nashville, Tennessee, 37212

Other trials in United States

About this study

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
Being tested: Levetiracetam (LEV) 500 mg, Placebo
Medical subject headings: Schizophrenia, Psychotic Disorders

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Levetiracetam (LEV) 500 mgDrug
Also called Keppra
The levetiracetam pill will look just like the placebo pill.
PlaceboDrug
The placebo pill will look just like the levetiracetam pill, but does not contain any levetiracetam.

Study groups in NCT04559529
Study group	Role	What they receive
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. Receives: 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. Receives: Drug: Levetiracetam (LEV) 500 mg; Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 2 hours after placebo administration

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

23 Sep 202031 Dec 2023

First posted23 Sep 2020
Study start23 Sep 2020
Primary completion31 Dec 2023
Study completion31 Dec 2023

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Schizophrenia; PsychosisStudies of the same condition, open and under way.
More trials run by Vanderbilt University Medical CenterThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Basic science
Allocation: Randomised
Intervention model: Crossover
Model description: 2-way crossover, double-blind, randomized controlled study
Masking: Triple blind
Who is masked: Participant, Care provider, Investigator
Enrolment: 62 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04559529
Sponsor's protocol ID: VEPP_200915
Status last verified: Feb 2024
First submitted: 16 Sep 2020
Last updated: 5 Feb 2024
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

RecruitingPhase 3
A Study to Evaluate the Long-term Safety and Tolerability of Xanomeline and Trospium Chloride for the Treatment of Psychiatric Disorders in Children and Adolescents
Schizophrenia, Autism-Related Irritability
Not yet recruitingObservational study
Sleep Monitoring for Early Detection of Relapse in People With Schizophrenia or Bipolar Disorder Receiving Usual Treatment
Bipolar Disorder (BD), SCHIZOPHRENIA 1 (Disorder)
Not yet recruitingPhase 1
Pharmacokinetics and Relative Bioavailability of Intranasal vs Intramuscular Olanzapine in Healthy Adult Participants
Healthy Adult Participants
Active, not recruiting
Designing and Evaluating a Classroom-Based Mental Health Programme for Adolescents.
Mental Health Promotion
Recruiting
MI-CBTech: A Mobile Intervention for Community Integration in Homeless-Experienced Veterans With SMI
Schizophrenia Spectrum Disorders, Psychotic Affective Disorders

All Schizophrenia; Psychosis trials

Study at a glance

From the registry record, last updated by the sponsor on 5 Feb 2024. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Pharmacological Modulation of Hippocampal Activity in Psychosis 2
ClinicalTrials.gov ID: NCT04559529
Acronym / sponsor ID: VEPP_200915
Conditions: Schizophrenia; Psychosis
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 62 participants (actual)
Lead sponsor: Vanderbilt University Medical CenterUniversity, hospital or other
Study start: 23 Sep 2020 (actual)
Primary completion: 31 Dec 2023 (actual)
Study completion: 31 Dec 2023 (actual)
First posted: 23 Sep 2020 (actual)
Results: Posted 5 Feb 2024

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Basic science
Allocation: Randomised
Intervention model: Crossover
Masking: Triple blind (participant, care provider, investigator)
Number of arms: 2
Model description: 2-way crossover, double-blind, randomized controlled study

Arm	Type	Receives
Levetiracetam (LEV), then Placebo	Experimental	Drug: Levetiracetam (LEV) 500 mg, Drug: PlaceboParticipants will first receive two 250mg LEV capsules on the same day. After one week, they will receive two placebo capsules on the same day.
Placebo, then Levetiracetam (LEV)	Experimental	Drug: Levetiracetam (LEV) 500 mg, Drug: PlaceboParticipants will first receive two placebo capsules on the same day. After one week, they will receive two 250mg LEV capsules on the same day.

Who may qualify

Ages: 18 to 65 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult, Older adult

Key inclusion criteria (12 listed)

Men and women age 18 - 65.
Communicative in English.
Provide voluntary, written informed consent.
Physically healthy by medical history.
BMI > 17.5 and < 45.

Key exclusion criteria (14 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Levetiracetam (LEV) 500 mgAlso: KeppraThe levetiracetam pill will look just like the placebo pill.	Drug	Levetiracetam (LEV), then Placebo, Placebo, then Levetiracetam (LEV)
PlaceboThe placebo pill will look just like the levetiracetam pill, but does not contain any levetiracetam.	Drug	Levetiracetam (LEV), then Placebo, Placebo, then Levetiracetam (LEV)

Primary outcome

Hippocampal Activity (Arterial Spin Labeling [ASL] Study) After Levetiracetam (LEV)
Time frame: 2 hours after LEV administration
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.
Hippocampal Activity (Arterial Spin Labeling [ASL] Study) After Placebo
Time frame: 2 hours after placebo administration
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.
Hippocampal Recruitment (Blood-Oxygen-Level-Dependent [BOLD] Study) After Levetiracetam (LEV)
Time frame: 2 hours after LEV administration
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.
Hippocampal Recruitment (Blood-Oxygen-Level-Dependent [BOLD] Study) After Placebo
Time frame: 2 hours after placebo administration
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.

Results and safety

Results posted to the registry on 5 Feb 2024, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Healthy Control Participants: Levetiracetam (LEV), Then Placebo	15	15
Healthy Control Participants: Placebo, Then Levetiracetam (LEV)	15	15
Patients With Schizophrenia: Levetiracetam (LEV), Then Placebo	15	14
Patients With Schizophrenia: Placebo, Then Levetiracetam (LEV)	17	16

Primary outcome: Hippocampal Activity (Arterial Spin Labeling [ASL] Study) After Levetiracetam (LEV)

Time frame: 2 hours after LEV administration. Mean (95% Confidence Interval). Unit: ml/100g/min

Measure	Healthy Control Participants: Levetiracetam (LEV), Then Placebo n = 15	Healthy Control Participants: Placebo, Then Levetiracetam (LEV) n = 14	Patients With Schizophrenia: Levetiracetam (LEV), Then Placebo n = 14	Patients With Schizophrenia: Placebo, Then Levetiracetam (LEV) n = 14
Value	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)

Population analysed: The overall number of participants analyzed is inconsistent with the numbers provided in the participant flow module due to MRI scanner or participant error during the collection of the ASL sequence. However, these participants still included useful imaging data collected in other imaging sequences during the study.

Primary outcome: Hippocampal Activity (Arterial Spin Labeling [ASL] Study) After Placebo

Time frame: 2 hours after placebo administration. Mean (95% Confidence Interval). Unit: ml/100g/min

Measure	Healthy Control Participants: Levetiracetam (LEV), Then Placebo n = 13	Healthy Control Participants: Placebo, Then Levetiracetam (LEV) n = 15	Patients With Schizophrenia: Levetiracetam (LEV), Then Placebo n = 13	Patients With Schizophrenia: Placebo, Then Levetiracetam (LEV) n = 14
Value	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)

Primary outcome: Hippocampal Recruitment (Blood-Oxygen-Level-Dependent [BOLD] Study) After Levetiracetam (LEV)

Time frame: 2 hours after LEV administration. Mean (95% Confidence Interval). Unit: BOLD percent signal change

Measure	Healthy Control Participants: Levetiracetam (LEV), Then Placebo n = 15	Healthy Control Participants: Placebo, Then Levetiracetam (LEV) n = 14	Patients With Schizophrenia: Levetiracetam (LEV), Then Placebo n = 13	Patients With Schizophrenia: Placebo, Then Levetiracetam (LEV) n = 11
Value	-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)

Population analysed: The overall number of participants analyzed is inconsistent with the numbers provided in the participant flow module due to MRI scanner or participant error during the collection of the recruitment data using the BOLD signal. However, these participants still included useful imaging data collected in other imaging sequences during the study.

Primary outcome: Hippocampal Recruitment (Blood-Oxygen-Level-Dependent [BOLD] Study) After Placebo

Time frame: 2 hours after placebo administration. Mean (95% Confidence Interval). Unit: BOLD percent signal change

Measure	Healthy Control Participants: Levetiracetam (LEV), Then Placebo n = 14	Healthy Control Participants: Placebo, Then Levetiracetam (LEV) n = 14	Patients With Schizophrenia: Levetiracetam (LEV), Then Placebo n = 12	Patients With Schizophrenia: Placebo, Then Levetiracetam (LEV) n = 14
Value	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)

Population analysed: The overall number of participants analyzed is inconsistent with the numbers provided in the participant flow module due to MRI scanner or participant error during the collection of the recruitment data using the BOLD signal. However, these participants still included useful imaging data collected in other imaging sequences during the study.

Adverse events

Time frame: Up to 4 hours after levetiracetam or placebo administration.. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Healthy Control Participants: Levetiracetam (LEV)	0 of 30 (0%)	0 of 30 (0%)	0 of 30
Healthy Control Participants: Placebo	0 of 30 (0%)	0 of 30 (0%)	0 of 30
Patients With Schizophrenia: Levetiracetam (LEV)	0 of 31 (0%)	0 of 31 (0%)	0 of 31
Patients With Schizophrenia: Placebo	0 of 30 (0%)	1 of 30 (3.3%)	0 of 30

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 5 Feb 2024.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Individual participant dataSharing planned: No

Related trials for Schizophrenia; Psychosis

RecruitingPhase 3
A Study to Evaluate the Long-term Safety and Tolerability of Xanomeline and Trospium Chloride for the Treatment of Psychiatric Disorders in Children and Adolescents
Schizophrenia, Autism-Related Irritability
Not yet recruitingObservational study
Sleep Monitoring for Early Detection of Relapse in People With Schizophrenia or Bipolar Disorder Receiving Usual Treatment
Bipolar Disorder (BD), SCHIZOPHRENIA 1 (Disorder)
Not yet recruitingPhase 1
Pharmacokinetics and Relative Bioavailability of Intranasal vs Intramuscular Olanzapine in Healthy Adult Participants
Healthy Adult Participants
Active, not recruiting
Designing and Evaluating a Classroom-Based Mental Health Programme for Adolescents.
Mental Health Promotion
Recruiting
MI-CBTech: A Mobile Intervention for Community Integration in Homeless-Experienced Veterans With SMI
Schizophrenia Spectrum Disorders, Psychotic Affective Disorders

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Stephan Heckers, MD principal investigator

Vanderbilt University Medical Center

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Levetiracetam (LEV) 500 mg in people with Schizophrenia; Psychosis, run by Vanderbilt University Medical Center at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 5 Feb 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 5 Feb 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Hippocampal Activity (Arterial Spin Labeling [ASL] Study) After Levetiracetam (LEV) (time frame: 2 hours after LEV administration). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04559529.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Feb 2024.