Schizophrenia
Conditions
Keywords
Schizophrenia
Brief 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.
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.
Interventions
DRUGLevetiracetam
Anticonvulsant drug
DRUGPlacebo
Placebo
Sponsors
VA Office of Research and Development
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* Diagnosis of schizophrenia or schizoaffective disorder * Good general health * Normal vital signs (blood pressure, pulse, respiration)
Exclusion criteria
* Substance abuse * Significant neurological disorders * Significant head trauma/injury * Pregnancy * MRI-specific
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Neurocognitive Function | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Resting-state Neuronal Response | Baseline and change from baseline to 4 weeks for each intervention | Neuronal response (measured via functional magnetic resonance imaging, fMRI) in the hippocampus during rest (fractional amplitude of low frequency fluctuations, fALFF). |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORJason R. Tregellas, PhD
Rocky Mountain Regional VA Medical Center, Aurora, CO
Participant flow
Recruitment details
67 patients were screened for eligibility between August 2018 and September 2023.
Pre-assignment details
41 out of 67 participants were randomized. Of those not randomized, 23 did not meet inclusion criteria and 3 declined to participate.
Participants by arm
| Arm | Count |
|---|---|
| Levetiracetam, Then Placebo 4 weeks of levetiracetam administration (125 mg pill, bid), followed by a 4-week washout, then 4 weeks of placebo pill administration (bid).
Levetiracetam: Anticonvulsant drug
Placebo: Placebo | 11 |
| Placebo, Then Levetiracetam 4 weeks of placebo administration (bid), followed by a 4-week washout, then 4 weeks of levetiracetam administration (125 mg pill, bid).
Levetiracetam: Anticonvulsant drug
Placebo: Placebo | 14 |
| Total | 25 |
Baseline characteristics
| Characteristic | Levetiracetam, Then Placebo | Total | Placebo, Then Levetiracetam |
|---|---|---|---|
| Age, Continuous | 45.82 years STANDARD_DEVIATION 16.65 | 47.04 years STANDARD_DEVIATION 14.95 | 48.00 years STANDARD_DEVIATION 14.03 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 6 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 8 Participants | 18 Participants | 10 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 6 Participants | 4 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 9 Participants | 16 Participants | 7 Participants |
| Region of Enrollment United States | 11 participants | 25 participants | 14 participants |
| Sex/Gender, Customized Female | 2 Participants | 6 Participants | 4 Participants |
| Sex/Gender, Customized Male | 8 Participants | 18 Participants | 10 Participants |
| Sex/Gender, Customized Other | 1 Participants | 1 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 30 | 0 / 27 |
| other Total, other adverse events | 16 / 30 | 16 / 27 |
| serious Total, serious adverse events | 0 / 30 | 0 / 27 |
Outcome results
Primary
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).
Time frame: 4 weeks
Population: All participants who received at least one dose of each intervention and completed all study visits were included.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Levetiracetam | Neurocognitive Function | RBANS at Baseline | 73.68 Total score | Standard Deviation 14.69 |
| Levetiracetam | Neurocognitive Function | Change from Baseline at 4 weeks | 3.36 Total score | Standard Deviation 7.29 |
| Placebo | Neurocognitive Function | RBANS at Baseline | 74.04 Total score | Standard Deviation 12.02 |
| Placebo | Neurocognitive Function | Change from Baseline at 4 weeks | 3.96 Total score | Standard Deviation 6.33 |
Secondary
Resting-state Neuronal Response
Neuronal response (measured via functional magnetic resonance imaging, fMRI) in the hippocampus during rest.
Time frame: 4 weeks