Trial Outcomes & Findings for Reducing Hippocampal Hyperactivity and Improving Cognition in Schizophrenia (NCT NCT03034356)
NCT ID: NCT03034356
Last Updated: 2025-07-14
Results Overview
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).
Recruitment status
COMPLETED
Study phase
PHASE1/PHASE2
Target enrollment
67 participants
Primary outcome timeframe
4 weeks
Results posted on
2025-07-14
Participant Flow
67 patients were screened for eligibility between October 2018 and September 2023.
41 out of 67 participants were randomized. Of those not randomized, 23 did not meet inclusion criteria and 3 declined to participate.
Participant milestones
| Measure |
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
|
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
|
|---|---|---|
|
Baseline
STARTED
|
20
|
21
|
|
Baseline
COMPLETED
|
16
|
16
|
|
Baseline
NOT COMPLETED
|
4
|
5
|
|
Post-Intervention 1 (4 Weeks)
STARTED
|
16
|
16
|
|
Post-Intervention 1 (4 Weeks)
COMPLETED
|
13
|
14
|
|
Post-Intervention 1 (4 Weeks)
NOT COMPLETED
|
3
|
2
|
|
Post-Washout (4 Weeks)
STARTED
|
13
|
14
|
|
Post-Washout (4 Weeks)
COMPLETED
|
11
|
14
|
|
Post-Washout (4 Weeks)
NOT COMPLETED
|
2
|
0
|
|
Post-Intervention 2 (4 Weeks)
STARTED
|
11
|
14
|
|
Post-Intervention 2 (4 Weeks)
COMPLETED
|
11
|
14
|
|
Post-Intervention 2 (4 Weeks)
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
| Measure |
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
|
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
|
|---|---|---|
|
Baseline
Lost to Follow-up
|
2
|
4
|
|
Baseline
Withdrawal by Subject
|
2
|
0
|
|
Baseline
Physician Decision
|
0
|
1
|
|
Post-Intervention 1 (4 Weeks)
Lost to Follow-up
|
1
|
0
|
|
Post-Intervention 1 (4 Weeks)
Withdrawal by Subject
|
1
|
2
|
|
Post-Intervention 1 (4 Weeks)
Physician Decision
|
1
|
0
|
|
Post-Washout (4 Weeks)
Withdrawal by Subject
|
2
|
0
|
Baseline Characteristics
Reducing Hippocampal Hyperactivity and Improving Cognition in Schizophrenia
Baseline characteristics by cohort
| Measure |
Levetiracetam, Then Placebo
n=11 Participants
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
|
Placebo, Then Levetiracetam
n=14 Participants
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
|
Total
n=25 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
45.82 years
STANDARD_DEVIATION 16.65 • n=5 Participants
|
48.00 years
STANDARD_DEVIATION 14.03 • n=7 Participants
|
47.04 years
STANDARD_DEVIATION 14.95 • n=5 Participants
|
|
Sex/Gender, Customized
Female
|
2 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
|
Sex/Gender, Customized
Male
|
8 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
18 Participants
n=5 Participants
|
|
Sex/Gender, Customized
Other
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
3 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
8 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
18 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
2 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
9 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
16 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
11 participants
n=5 Participants
|
14 participants
n=7 Participants
|
25 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 4 weeksPopulation: All participants who received at least one dose of each intervention and completed all study visits were included.
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).
Outcome measures
| Measure |
Levetiracetam
n=25 Participants
Participants who received levetiracetam administration (125 mg pill, bid) for either the first or last 4 weeks of the study.
|
Placebo
n=25 Participants
Participants who received placebo administration (125 mg pill, bid) for either the first or last 4 weeks of the study.
|
|---|---|---|
|
Neurocognitive Function
RBANS at Baseline
|
73.68 Total score
Standard Deviation 14.69
|
74.04 Total score
Standard Deviation 12.02
|
|
Neurocognitive Function
Change from Baseline at 4 weeks
|
3.36 Total score
Standard Deviation 7.29
|
3.96 Total score
Standard Deviation 6.33
|
SECONDARY outcome
Timeframe: 4 weeksNeuronal response (measured via functional magnetic resonance imaging, fMRI) in the hippocampus during rest.
Outcome measures
Outcome data not reported
Adverse Events
Levetiracetam
Serious events: 0 serious events
Other events: 16 other events
Deaths: 0 deaths
Placebo
Serious events: 0 serious events
Other events: 16 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Levetiracetam
n=30 participants at risk
Participants who received levetiracetam administration (125 mg pill, bid) for either the first or last 4 weeks of the study.
|
Placebo
n=27 participants at risk
Participants who received placebo administration (125 mg pill, bid) for either the first or last 4 weeks of the study.
|
|---|---|---|
|
Gastrointestinal disorders
Abdominal pain
|
3.3%
1/30 • 4 weeks for each intervention
All participants who received at least one dose of intervention.
|
11.1%
3/27 • 4 weeks for each intervention
All participants who received at least one dose of intervention.
|
|
Psychiatric disorders
Hallucinations
|
3.3%
1/30 • 4 weeks for each intervention
All participants who received at least one dose of intervention.
|
11.1%
3/27 • 4 weeks for each intervention
All participants who received at least one dose of intervention.
|
|
Nervous system disorders
Headache
|
10.0%
3/30 • 4 weeks for each intervention
All participants who received at least one dose of intervention.
|
7.4%
2/27 • 4 weeks for each intervention
All participants who received at least one dose of intervention.
|
|
Psychiatric disorders
Irritability
|
10.0%
3/30 • 4 weeks for each intervention
All participants who received at least one dose of intervention.
|
0.00%
0/27 • 4 weeks for each intervention
All participants who received at least one dose of intervention.
|
|
Psychiatric disorders
Paranoia
|
3.3%
1/30 • 4 weeks for each intervention
All participants who received at least one dose of intervention.
|
11.1%
3/27 • 4 weeks for each intervention
All participants who received at least one dose of intervention.
|
|
General disorders
Sedation or Drowsiness
|
20.0%
6/30 • 4 weeks for each intervention
All participants who received at least one dose of intervention.
|
11.1%
3/27 • 4 weeks for each intervention
All participants who received at least one dose of intervention.
|
|
Eye disorders
Visual Disturbance
|
3.3%
1/30 • 4 weeks for each intervention
All participants who received at least one dose of intervention.
|
7.4%
2/27 • 4 weeks for each intervention
All participants who received at least one dose of intervention.
|
Additional Information
Jason Tregellas, PhD
VA Eastern Colorado Health Care System
Phone: 303-724-6232
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place