SchizophreniaPhase 1/2NCT03034356
Reducing Hippocampal Hyperactivity and Improving Cognition in Schizophrenia
A Phase 1/2 study testing Levetiracetam in people with Schizophrenia, run by VA Office of Research and Development at 1 site in United States.
Trial summary
This study plans to learn more about the effects of levetiracetam (LEV) on brain activity and cognition in schizophrenia and schizoaffective disorder. Levetiracetam is an anti-seizure drug, also called an anticonvulsant. Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Schizophrenia
- What is being tested?
- Levetiracetam
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 67 participants
- Where
- 1 siteUnited States
- Study dates
- 15 Aug 2018to 30 Jun 2024
- Phase
- Phase 1/2
- 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
- Diagnosis of schizophrenia or schizoaffective disorder
- Good general health
- Normal vital signs (blood pressure, pulse, respiration)
Who cannot join
- Substance abuse
- Significant neurological disorders
- Significant head trauma/injury
- Pregnancy
- MRI-specific exclusion criteria, e.g.,:
- claustrophobia
- weight>400 lbs
- metal in the body
Trial locations and contacts
1 site in 1 country.
United States1 site
Rocky Mountain Regional VA Medical Center, Aurora, CO
Aurora, Colorado, 80045-7211
About this study
This study plans to learn more about the effects of levetiracetam (LEV) on brain activity and cognition in schizophrenia and schizoaffective disorder. Levetiracetam is an anti-seizure drug, also called an anticonvulsant.
Read the detailed description
Cognitive symptoms are not currently well-managed in Veterans with schizophrenia, leading to substantially diminished quality of life. Improved treatment strategies clearly are needed. Recent studies suggest taht an overactive hippocampus is associated with cognitive deficits in the illness. Based on findings that the anti-epileptic drug levetiracetam (LEV) reduces hippocampal activity and improves cognition in other clinical populations while being safe and well-tolerated, this study will examine the effects of the drug on hippocampal activity and cognition in Veterans with schizophrenia. In this crossover design, participants will take LEV for 4 weeks and placebo pills for 4 weeks, but will not know the order in which they are taking them.
- Conditions
- Schizophrenia
- Being tested
- Levetiracetam, Placebo
- Keywords
- Schizophrenia
- Medical subject headings
- Schizophrenia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LevetiracetamDrug
Also called Keppra
Anticonvulsant drug
PlaceboDrug
Placebo
| Study group | Role | What they receive |
|---|---|---|
| Levetiracetam, Then Placebo | Experimental | 4 weeks of levetiracetam administration (125 mg pill, bid), followed by a 4-week washout, then 4 weeks of placebo pill administration (bid). Receives: Drug: Levetiracetam; Drug: Placebo |
| Placebo, Then Levetiracetam | Experimental | 4 weeks of placebo administration (bid), followed by a 4-week washout, then 4 weeks of levetiracetam administration (125 mg pill, bid). Receives: Drug: Levetiracetam; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Neurocognitive Function
Cognitive function as measured by the Repeatable Battery for the Assessment of Neurological Status (RBANS; total score). Scores are scaled with a mean of 100 and standard deviation of 15 (higher scores indicating better outcome).
Measured: Baseline and change from baseline to 4 weeks for each intervention
Secondary outcomes (1)
Resting-state Neuronal Response
Neuronal response (measured via functional magnetic resonance imaging, fMRI) in the hippocampus during rest (fractional amplitude of low frequency fluctuations, fALFF).
Measured: Baseline and change from baseline to 4 weeks for each intervention
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jan 2017 (estimated)
- Study start15 Aug 2018
- Primary completion30 Jun 2024
- Study completion30 Jun 2024
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 SchizophreniaStudies of the same condition, open and under way.
- More trials run by VA Office of Research and DevelopmentThe 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 1/2
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 67 participants (actual)
Sponsor and investigators
- Lead sponsor
- VA Office of Research and Development
- Sponsor type
- US federal agency
- Responsible party
- Sponsor
- Investigators
- Jason R. Tregellas, PhD, Principal investigator, Rocky Mountain Regional VA Medical Center, Aurora, CO
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03034356
- Sponsor's protocol ID
- MHBB-006-16S
- Other IDs
- I01CX001414
- Status last verified
- Jul 2026
- First submitted
- 25 Jan 2017
- Last updated
- 11 Aug 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: A de-identified, anonymized dataset will be created and shared.
Study at a glance
From the registry record, last updated by the sponsor on 11 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Reducing Hippocampal Hyperactivity and Improving Cognition in Schizophrenia
- ClinicalTrials.gov ID
- NCT03034356
- Acronym / sponsor ID
- MHBB-006-16S
- Conditions
- Schizophrenia
- Keywords
- Schizophrenia
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 67 participants (actual)
- Lead sponsor
- VA Office of Research and DevelopmentUS federal agency
- Study start
- 15 Aug 2018 (actual)
- Primary completion
- 30 Jun 2024 (actual)
- Study completion
- 30 Jun 2024 (actual)
- First posted
- 27 Jan 2017 (estimated)
- Results
- Posted 14 Jul 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study plans to learn more about the effects of levetiracetam (LEV) on brain activity and cognition in schizophrenia and schizoaffective disorder. Levetiracetam is an anti-seizure drug, also called an anticonvulsant.
Detailed description
Cognitive symptoms are not currently well-managed in Veterans with schizophrenia, leading to substantially diminished quality of life. Improved treatment strategies clearly are needed. Recent studies suggest taht an overactive hippocampus is associated with cognitive deficits in the illness. Based on findings that the anti-epileptic drug levetiracetam (LEV) reduces hippocampal activity and improves cognition in other clinical populations while being safe and well-tolerated, this study will examine the effects of the drug on hippocampal activity and cognition in Veterans with schizophrenia. In this crossover design, participants will take LEV for 4 weeks and placebo pills for 4 weeks, but will not know the order in which they are taking them.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Levetiracetam, Then Placebo | Experimental | Drug: Levetiracetam, Drug: Placebo4 weeks of levetiracetam administration (125 mg pill, bid), followed by a 4-week washout, then 4 weeks of placebo pill administration (bid). |
| Placebo, Then Levetiracetam | Experimental | Drug: Levetiracetam, Drug: Placebo4 weeks of placebo administration (bid), followed by a 4-week washout, then 4 weeks of levetiracetam administration (125 mg pill, bid). |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Diagnosis of schizophrenia or schizoaffective disorder
- Good general health
- Normal vital signs (blood pressure, pulse, respiration)
Key exclusion criteria (8 listed)
- Substance abuse
- Significant neurological disorders
- Significant head trauma/injury
- Pregnancy
- MRI-specific exclusion criteria, e.g.,:
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 |
|---|---|---|
| LevetiracetamAlso: KeppraAnticonvulsant drug | Drug | Levetiracetam, Then Placebo, Placebo, Then Levetiracetam |
| PlaceboPlacebo | Drug | Levetiracetam, Then Placebo, Placebo, Then Levetiracetam |
Primary outcome
Neurocognitive Function
Time frame: Baseline and change from baseline to 4 weeks for each intervention
Cognitive function as measured by the Repeatable Battery for the Assessment of Neurological Status (RBANS; total score). Scores are scaled with a mean of 100 and standard deviation of 15 (higher scores indicating better outcome).
1 secondary outcome
Resting-state Neuronal Response
Time frame: Baseline and change from baseline to 4 weeks for each intervention
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Aug 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Yes. A de-identified, anonymized dataset will be created and shared.
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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.
Jason R. Tregellas, PhD principal investigator
Rocky Mountain Regional VA Medical Center, Aurora, CO
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Levetiracetam in people with Schizophrenia, run by VA Office of Research and Development 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 3 inclusion and 8 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 11 Aug 2026. 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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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 14 Jul 2025). 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?
Neurocognitive Function (time frame: Baseline and change from baseline to 4 weeks for each intervention). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 11 Aug 2026.