Schizophrenia
Conditions
Brief summary
Levetiracetam (LEV: (S)-α-ethyl-2-oxo-pyrrolidine acetamide) is an anticonvulsant/antiepileptic drug. The specific aim of this study is to assess the efficacy of low-dose LEV in reducing hippocampal activity in schizophrenia. The investigators also hypothesize that LEV will improve neurocognition in participants with schizophrenia.
Detailed description
LEV is typically administered in twice-daily doses of 500-1500 mg for the treatment of epilepsy; these doses are generally well tolerated (Patsalos, 2000). Most relevant to the proposed study, LEV (125 mg twice-daily, two week administration) has been shown to reduce hippocampal hyperactivity and improves cognition in patients with mild cognitive impairment (MCI). The proposed study will administer 125 mg of immediate release LEV twice-daily for two weeks. This dose was chosen to potentially maximize efficacy while minimizing side effects. The proposed dose is substantially lower than the most common dose used clinically for epilepsy treatment of 3000 mg/day.
Interventions
DRUGLevetiracetam
DRUGPlacebo
Sponsors
University of Colorado, Denver
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
No
Inclusion criteria
* Diagnosis of schizophrenia or schizoaffective disorder * Good general health * Normal vital signs (blood pressure, pulse, cardiac, pulmonary, abdominal, neurological exam) * Normal renal function (as assessed by a metabolic panel at screening if results current within three months are not already available)
Exclusion criteria
1. Substance abuse 2. Significant neurological disorders 3. Significant head trauma/injury 4. Left-handedness 5. Pregnancy 6. MRI-specific
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Resting-state Neuronal Response | 2 weeks | Mean neuronal response (measured via functional magnetic resonance imaging, fMRI) in the hippocampus during rest. This was measured as fractional amplitude of low frequency fluctuations (fALFF), which is a metric derived from resting-state fMRI that represents the power of regional spontaneous, intrinsic brain activity. This was calculated as the ratio of the low-frequency band power (0.01-0.1 Hz) to the total power across the entire frequency range of the Blood Oxygen Level-Dependent (BOLD) signal. Values generally range from 0 to 1, with higher values indicating a larger fraction of low-frequency fluctuations. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Neurocognitive Function | 2 weeks | Cognitive function as measured by the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) cognitive test battery. The RBANS consists of 12 subtests; raw scores from the 12 subtests are converted into age-based standardized index scores (mean=100, standard deviation \[SD\]=15) across five cognitive domains (Immediate Memory, Visuospatial/Constructional, Language, Attention, and Delayed Memory). The five index scores are summed, then translated to a final total scale score (mean=100, SD=15) using the conversion table in the RBANS manual. RBANS total scores range from 40-160, with lower scores indicating worse cognitive function. Scores one SD below the mean of 100 are indicative of mild cognitive impairment or the lower end of normal cognitive function, scores two SDs below the mean suggest moderate cognitive impairment, and scores three SD below the mean suggest severe cognitive impairment. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORJason Tregellas, Ph.D.
University of Colorado, Denver
Participant flow
Recruitment details
26 participants were screened for eligibility.
Pre-assignment details
18 out of 26 participants were randomized. Of those not randomized, 7 did not meet inclusion criteria and 1 declined to participate.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 51.00 years STANDARD_DEVIATION 11.03 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 9 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 13 Participants |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 16 | 0 / 16 |
| other Total, other adverse events | 5 / 16 | 3 / 16 |
| serious Total, serious adverse events | 0 / 16 | 0 / 16 |
Outcome results
None listed