Schizophrenia; Psychosis
Conditions
Keywords
Hippocampus
Brief summary
The purpose of this study is to test whether administration of levetiracetam (LEV), a commonly used anti-epileptic that alters neurotransmitter release, can reduce hippocampal hyperactivity. Specifically, we will utilize two functional magnetic resonance imaging (MRI) techniques: 1) blood oxygen level dependence (BOLD) contrast will assess activity with a visual scene processing task that engages the anterior hippocampus and 2) arterial spin labeling (ASL) will assess baseline activity. This study will also assess whether patients have improvement in their symptoms after receiving LEV. Previous studies in people with psychotic disorders have shown that the hippocampus is hyperactive and more activity correlates with worsening of clinical symptoms. Therefore, the aim of this study is to use an intervention to further understand the underlying mechanisms of the hippocampus in psychosis.
Interventions
Levetiracetam (LEV) regulates neuronal synaptic exocytosis and calcium-induced neurotransmitter release and has a therapeutic effect on the excitation-inhibition balance of the hippocampus.
Sponsors
Vanderbilt University Medical Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
for psychosis subjects: 1. Men and women age 18 - 65. 2. Communicative in English. 3. Provide voluntary, written informed consent. 4. Physically healthy by medical history. 5. BMI \> 17.5 and \< 45. 6. Diagnosis of a psychotic disorder confirmed by Structured Clinical Interview for DSM-V (SCID) or diagnostic interview with a trained clinician. 7. Stable medication regimen over at least the past two weeks, including the use of either an oral or intramuscular administration of an antipsychotic medication. 8. For females, no longer of child-bearing potential, or agreeing to practice effective contraception during the study; and, 9. For females of child-bearing potential, must have negative urine pregnancy test at time of screening visit and before each testing day. 10. Not breastfeeding/nursing at time of screening or at any time during the study. Inclusion criteria for healthy controls All of the above except for subjects will be psychiatrically healthy and not taking psychotropic or potentially psychoactive prescription medication.
Exclusion criteria
for psychosis subjects 1. Age less than 18 or greater than 65. 2. Not communicative in English. 3. Unable to provide written informed consent. 4. Current medical or neurological illness. 5. History of severe head trauma. 6. BMI \< 17.5 or \> 45. 7. Meets criteria for diagnosis of substance or alcohol use disorder within the past month. 8. Positive urine pregnancy test at time of screening, before each testing day, or any potential concern for pregnancy at any time during the study. 9. Breastfeeding/nursing at time of screening or at any time during the study. 10. Conditions that preclude MR scanning 11. Conditions that preclude study drug administration
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Hippocampal Activity (Arterial Spin Labeling [ASL] Study) | 2 hours and 2 weeks after administration | Change in ASL signal after drug administration |
| Hippocampal Recruitment (BOLD Study) | 2 hours and 2 weeks after administration | Change in BOLD signal after drug administration |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cognitive Symptoms | 2 weeks after administration | Change in eye-tracking relational memory task |
| Positive and Negative Symptoms | 2 weeks after administration | Change PANSS score |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Levetiracetam (LEV) 500 mg Participants will take their first dose of 500 mg LEV. After a two hour time window, the participants will complete MRI study. After MRI, patients will begin a 2-week intervention with 250 mg BID oral LEV.
Levetiracetam 500 mg: Levetiracetam (LEV) regulates neuronal synaptic exocytosis and calcium-induced neurotransmitter release and has a therapeutic effect on the excitation-inhibition balance of the hippocampus. | 0 |
| Total | 0 |
Baseline characteristics
| Characteristic | — |
|---|---|
| Region of Enrollment United States | — participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 1 |
| other Total, other adverse events | 0 / 1 |
| serious Total, serious adverse events | 0 / 1 |
Outcome results
Primary
Hippocampal Activity (Arterial Spin Labeling [ASL] Study)
Change in ASL signal after drug administration
Time frame: 2 hours and 2 weeks after administration
Population: Data were collected for a single subject, but study design was changed and study was discontinued.
Primary
Hippocampal Recruitment (BOLD Study)
Change in BOLD signal after drug administration
Time frame: 2 hours and 2 weeks after administration
Population: Data were collected for a single subject, but study design was changed and study was discontinued.
Secondary
Cognitive Symptoms
Change in eye-tracking relational memory task
Time frame: 2 weeks after administration
Population: No data were collected.
Secondary
Positive and Negative Symptoms
Change PANSS score
Time frame: 2 weeks after administration
Population: Healthy participant; outcome measure does not apply