Effects of Low-dose Levetiracetam on Clinical Symptoms, Cognition and Hippocampal Hyperactivity in Schizophrenia

University of Colorado Denver (CU Denver)

Status: Completed

Conditions: Schizophrenia

Treatments: Drug: Levetiracetam; Drug: Placebo

Study type: Interventional

Funder types: Other

Identifiers

NCT02647437

13-1495

Details and patient eligibility

About

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.

Full 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.

Enrollment: 18 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

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 exclusion criteria (e.g., claustrophobia, weight > 450lbs, metal in the body)

Trial design

Primary purpose: Other

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Triple Blind

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18 participants in 2 patient groups

Levetiracetam, Then Placebo

Experimental group

Description:

2 weeks of levetiracetam administration (125 mg pill, bid), followed by a 1-2 week washout, then 2 weeks of placebo pill administration (bid).

Treatment:

Drug: Placebo

Drug: Levetiracetam

Placebo, Then Levetiracetam

Experimental group

Description:

2 weeks of placebo pill administration (bid), followed by a 1-2 week washout, then 2 weeks of levetiracetam administration (125 mg pill, bid).

Treatment:

Drug: Placebo

Drug: Levetiracetam