Trial Outcomes & Findings for Effects of Low-dose Levetiracetam on Clinical Symptoms, Cognition and Hippocampal Hyperactivity in Schizophrenia (NCT NCT02647437)
NCT ID: NCT02647437
Last Updated: 2026-08-21
Results Overview
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.
COMPLETED
NA
18 participants
2 weeks
2026-08-21
Participant Flow
26 participants were screened for eligibility.
18 out of 26 participants were randomized. Of those not randomized, 7 did not meet inclusion criteria and 1 declined to participate.
Participant milestones
| Measure |
Levetiracetam, Then Placebo
2 weeks of levetiracetam administration (125 mg pill, bid), followed by a 1-2 week washout, then 2 weeks of placebo pill administration (bid).
|
Placebo, Then Levetiracetam
2 weeks of placebo pill administration (bid), followed by a 1-2 week washout, then 2 weeks of levetiracetam administration (125 mg pill, bid).
|
|---|---|---|
|
Intervention Arm 1
STARTED
|
9
|
9
|
|
Intervention Arm 1
COMPLETED
|
8
|
8
|
|
Intervention Arm 1
NOT COMPLETED
|
1
|
1
|
|
Intervention Arm 2
STARTED
|
8
|
8
|
|
Intervention Arm 2
COMPLETED
|
6
|
7
|
|
Intervention Arm 2
NOT COMPLETED
|
2
|
1
|
Reasons for withdrawal
| Measure |
Levetiracetam, Then Placebo
2 weeks of levetiracetam administration (125 mg pill, bid), followed by a 1-2 week washout, then 2 weeks of placebo pill administration (bid).
|
Placebo, Then Levetiracetam
2 weeks of placebo pill administration (bid), followed by a 1-2 week washout, then 2 weeks of levetiracetam administration (125 mg pill, bid).
|
|---|---|---|
|
Intervention Arm 1
Withdrawal by Subject
|
1
|
0
|
|
Intervention Arm 1
Non-compliance (failed urine toxicology screen)
|
0
|
1
|
|
Intervention Arm 2
Physician Decision
|
1
|
1
|
|
Intervention Arm 2
Non-compliance (failed urine toxicology screen)
|
1
|
0
|
Baseline Characteristics
Effects of Low-dose Levetiracetam on Clinical Symptoms, Cognition and Hippocampal Hyperactivity in Schizophrenia
Baseline characteristics by cohort
| Measure |
Levetiracetam, Then Placebo
n=9 Participants
2 weeks of levetiracetam administration (125 mg pill, bid), followed by a 1-2 week washout, then 2 weeks of placebo pill administration (bid).
|
Placebo, Then Levetiracetam
n=9 Participants
2 weeks of placebo pill administration (bid), followed by a 1-2 week washout, then 2 weeks of levetiracetam administration (125 mg pill, bid).
|
Total
n=18 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
45.44 years
STANDARD_DEVIATION 12.57 • n=5 Participants
|
56.22 years
STANDARD_DEVIATION 5.63 • n=109 Participants
|
51.00 years
STANDARD_DEVIATION 11.03 • n=133 Participants
|
|
Sex: Female, Male
Female
|
3 Participants
n=5 Participants
|
3 Participants
n=109 Participants
|
6 Participants
n=133 Participants
|
|
Sex: Female, Male
Male
|
6 Participants
n=5 Participants
|
6 Participants
n=109 Participants
|
12 Participants
n=133 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=109 Participants
|
0 Participants
n=133 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=109 Participants
|
0 Participants
n=133 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=109 Participants
|
0 Participants
n=133 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
5 Participants
n=109 Participants
|
5 Participants
n=133 Participants
|
|
Race (NIH/OMB)
White
|
9 Participants
n=5 Participants
|
4 Participants
n=109 Participants
|
13 Participants
n=133 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=109 Participants
|
0 Participants
n=133 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=109 Participants
|
0 Participants
n=133 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
1 Participants
n=5 Participants
|
0 Participants
n=109 Participants
|
1 Participants
n=133 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
8 Participants
n=5 Participants
|
9 Participants
n=109 Participants
|
17 Participants
n=133 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=109 Participants
|
0 Participants
n=133 Participants
|
PRIMARY outcome
Timeframe: 2 weeksPopulation: 15 participants completed the Levetiracetam arm of the study and 14 completed the Placebo arm. fMRI data were not analyzed for 3 participants for the Levetiracetam arm and for 2 participants for the Placebo arm, due to technical difficulties or movement during scanning.
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.
Outcome measures
| Measure |
Placebo
n=12 Participants
Participants who received placebo administration (125 mg pill, bid) for 2 weeks during the study.
|
Levetiracetam
n=12 Participants
Participants who received levetiracetam administration (125 mg pill, bid) for 2 weeks during the study.
|
|---|---|---|
|
Resting-state Neuronal Response
|
0.51 ratio
Standard Deviation 0.10
|
0.76 ratio
Standard Deviation 0.13
|
SECONDARY outcome
Timeframe: 2 weeksPopulation: 15 participants completed the Levetiracetam arm of the study and 14 completed the Placebo arm. RBANS data were missing for 2 participants for the Levetiracetam arm and for 3 participants for the placebo arm, due to technical difficulties.
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.
Outcome measures
| Measure |
Placebo
n=11 Participants
Participants who received placebo administration (125 mg pill, bid) for 2 weeks during the study.
|
Levetiracetam
n=13 Participants
Participants who received levetiracetam administration (125 mg pill, bid) for 2 weeks during the study.
|
|---|---|---|
|
Neurocognitive Function
|
79.7 units on a scale
Standard Deviation 12.8
|
79.3 units on a scale
Standard Deviation 26.7
|
Adverse Events
Levetiracetam
Placebo
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Levetiracetam
n=16 participants at risk
2 weeks of levetiracetam administration (125 mg pill, bid)
|
Placebo
n=16 participants at risk
2 weeks of placebo pill administration (bid)
|
|---|---|---|
|
Psychiatric disorders
Paranoia
|
6.2%
1/16 • 2 weeks for each intervention arm
All participants who received at least one dose of intervention
|
0.00%
0/16 • 2 weeks for each intervention arm
All participants who received at least one dose of intervention
|
|
General disorders
Sedation or Drowsiness
|
12.5%
2/16 • 2 weeks for each intervention arm
All participants who received at least one dose of intervention
|
6.2%
1/16 • 2 weeks for each intervention arm
All participants who received at least one dose of intervention
|
|
Gastrointestinal disorders
Abdominal Pain
|
0.00%
0/16 • 2 weeks for each intervention arm
All participants who received at least one dose of intervention
|
6.2%
1/16 • 2 weeks for each intervention arm
All participants who received at least one dose of intervention
|
|
Musculoskeletal and connective tissue disorders
Joint Pain
|
0.00%
0/16 • 2 weeks for each intervention arm
All participants who received at least one dose of intervention
|
6.2%
1/16 • 2 weeks for each intervention arm
All participants who received at least one dose of intervention
|
|
Nervous system disorders
Concentration difficulties
|
6.2%
1/16 • 2 weeks for each intervention arm
All participants who received at least one dose of intervention
|
0.00%
0/16 • 2 weeks for each intervention arm
All participants who received at least one dose of intervention
|
|
General disorders
Chest Pain
|
0.00%
0/16 • 2 weeks for each intervention arm
All participants who received at least one dose of intervention
|
6.2%
1/16 • 2 weeks for each intervention arm
All participants who received at least one dose of intervention
|
|
Hepatobiliary disorders
Hypersalivation/Drooling
|
0.00%
0/16 • 2 weeks for each intervention arm
All participants who received at least one dose of intervention
|
6.2%
1/16 • 2 weeks for each intervention arm
All participants who received at least one dose of intervention
|
|
General disorders
Tremor
|
6.2%
1/16 • 2 weeks for each intervention arm
All participants who received at least one dose of intervention
|
0.00%
0/16 • 2 weeks for each intervention arm
All participants who received at least one dose of intervention
|
|
Metabolism and nutrition disorders
Anorexia/Lack of Appetite
|
6.2%
1/16 • 2 weeks for each intervention arm
All participants who received at least one dose of intervention
|
0.00%
0/16 • 2 weeks for each intervention arm
All participants who received at least one dose of intervention
|
|
Gastrointestinal disorders
Nausea/vomiting
|
0.00%
0/16 • 2 weeks for each intervention arm
All participants who received at least one dose of intervention
|
6.2%
1/16 • 2 weeks for each intervention arm
All participants who received at least one dose of intervention
|
|
General disorders
Dry Mouth
|
6.2%
1/16 • 2 weeks for each intervention arm
All participants who received at least one dose of intervention
|
0.00%
0/16 • 2 weeks for each intervention arm
All participants who received at least one dose of intervention
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place