Official Title: “Efficacy of Fluoxetine in Reducing Ictal Hypoventilation in Patients With Partial Epilepsy”

The purpose of this study is to determine the effects of fluoxetine on breathing mechanisms during seizures. Patients with partial epilepsy commonly have changes in their breathing mechanisms during seizures. These changes may increase the risk of serious side effects from seizures, including sudden unexplained death in epilepsy (SUDEP), which affects 2-10 per 1000 patients with epilepsy each year. Fluoxetine (Prozac) may help to stimulate breathing through its actions in the brain and has been shown to improve breathing changes seen with seizures in certain animals. Fluoxetine is in a class of medications called selective serotonin reuptake inhibitors (SSRIs). It works by increasing the amount of serotonin, a natural substance in the brain, at synapses, the junctions at which nerve cells in the brain communicate. Fluoxetine is currently approved by the United States Food and Drug Administration (FDA) for the treatment of patients with Major Depressive Disorder, Obsessive Compulsive Disorder, Bulimia Nervosa, Panic Disorder and Premenstrual Dysphoric Disorder.

Study Type: Interventional

Study Design: Supportive Care, Randomized, Double Blind (Subject, Investigator), Placebo Control, Parallel Assignment

Study Primary Completion Date: August 2010

Patients who consent to participate in the study will come to the clinic one week prior to the scheduled date of hospitalization in the Epilepsy Monitoring Unit (EMU). At this visit a complete physical examination including vital signs and complete neurological examination, mental status, cranial nerves, motor examination, deep tendon reflexes, sensory examination, coordinator and gait will be performed. Baseline laboratory studies including complete blood count, serum electrolytes, renal and liver function studies and serum pregnancy test for female patients will also be performed. Study medication will be dispensed at this visit.

Patients will be randomized to receive either 20 mg/day of fluoxetine (one pill) or placebo (one pill), to be started one week prior to the scheduled hospital admission date. The dose will be increased to two pills per day on day 1 of hospitalization bringing the total dose of fluoxetine to 40 mg/day in patients randomized to receive this medication. On the day of discharge from the hospital, the study medication will be reduced to 1 pill per day and the patient will be instructed to stop the medication one week following discharge. A follow-up clinic visit for the patient will be scheduled 1 month following hospital discharge, as is the usual protocol for patients undergoing VET at our institution.

Intervention(s) in this Clinical Trial

• Drug: Fluoxetine
  • Subjects randomized to fluoxetine will receive 20mg/day (one pill) for one week. The dose will be increased to 40mg/day (two pills) for the duration of hospitalization for VET. The dose will be decreased to 20 mg/day (one pill) from the day of hospital discharge for one week, at which time the medication will be discontinued.
• Drug: Placebo
  • Subjects randomized to fluoxetine will receive 20mg/day (one pill) for one week. The dose will be increased to 40mg/day (two pills) for the duration of hospitalization for VET. The dose will be decreased to 20 mg/day (one pill) from the day of hospital discharge for one week, at which time the medication will be discontinued.

Arms, Groups and Cohorts in this Clinical Trial

• Active Comparator: fluoxetine
  • Patients will be randomized to receive either 20 mg/day of fluoxetine (one pill) or placebo (one pill), to be started one week prior to the scheduled hospital admission date. The dose will be increased to two pills per day on day 1 of hospitalization bringing the total dose of fluoxetine to 40 mg/day in patients randomized to receive this medication. On the day of discharge from the hospital, the study medication will be reduced to 1 pill per day and the patient will be instructed to stop the medication one week following discharge.
• Placebo Comparator: Placebo
  • Patients will be randomized to receive either 20 mg/day of fluoxetine (one pill) or placebo (one pill), to be started one week prior to the scheduled hospital admission date. The dose will be increased to two pills per day on day 1 of hospitalization. On the day of discharge from the hospital, the study medication will be reduced to 1 pill per day and the patient will be instructed to stop the medication one week following discharge.

Primary Measures

• The primary end point for this study is a 50% fluoxetine-related reduction in the number of seizures with associated oxygen desaturations below 90% compared with placebo.
  • Time Frame: 6 weeks
    Safety Issue?: Yes

Secondary Measures

• The secondary end point is, in the group of seizures with desaturations below 90%, a 30% fluoxetine-related improvement in the oxygen desaturation nadir relative to placebo.
  • Time Frame: 6 weeks
    Safety Issue?: Yes

Inclusion Criteria:

• 1. Adult patients with temporal lobe epilepsy, aged 18-65.
• 2. Medical intractability of seizures such that VET to determine candidacy for epilepsy surgery is determined to be clinically appropriate for the patient by the primary treating epileptologist.
• 3. Intelligence Quotient >70.
• 4. Native English speaker or adequate fluency in English to provide informed consent.
• 5. Female patients of child-bearing potential must be using an acceptable method of contraception, including abstinence.

Exclusion Criteria:

• 1. Progressive neurological disease.
• 2. Severe depression, bipolar disease or psychosis.
• 3. History of suicidal ideation or intent.
• 4. Clinically significant concurrent medical illness, including hepatic or renal insufficiency and diabetes.
• 5. Pregnant or lactating women.
• 6. Current heavy alcohol or illicit drug use.
• 7. Patients already taking fluoxetine or other selective serotonin reuptake inhibitors (SSRIs).
• 8. Concurrent use of monoaminoxidase inhibitors, antipsychotic agents, antidepressant agents other than SSRIs or frequent use of triptan agents.
• 9. History of a previous allergic reaction or adverse effects with SSRIs.
• 10. History of serotonin syndrome.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 65 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: University of California, Davis

Overall Clinical Trial Officials and Contacts

Lisa M Bateman, MD, FRCPC Principal Investigator University of California, Davis  

Overall Contact: Roxana Hupcey, CCRP 916-734-6244 roxana.hupcey@ucdmc.ucdavis.edu

Information obtained from ClinicalTrials.gov on February 08, 2010

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00986310

Study ID Number: 200917358

ClinicalTrials.gov Identifier: NCT00986310

Health Authority: United States: Institutional Review Board