Efficacy of Fluoxetine in Reducing Ictal Hypoventilation in Patients With Partial Epilepsy

This study has been completed.
Sponsor:
Collaborator:
Citizens United for Research in Epilepsy (CURE)
Information provided by (Responsible Party):
Lisa M. Bateman, MD, University of California, Davis
ClinicalTrials.gov Identifier:
NCT00986310
First received: September 25, 2009
Last updated: November 2, 2012
Last verified: November 2012
  Purpose

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.


Condition Intervention
Uncontrolled Partial Epilepsy
Ictal Hypoventilation
Drug: Fluoxetine
Drug: Placebo

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Supportive Care
Official Title: Efficacy of Fluoxetine in Reducing Ictal Hypoventilation in Patients With Partial Epilepsy

Resource links provided by NLM:


Further study details as provided by University of California, Davis:

Primary Outcome 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 ] [ Designated as safety issue: Yes ]

Secondary Outcome 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 ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 60
Study Start Date: August 2009
Study Completion Date: June 2012
Primary Completion Date: February 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
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.
Other Name: Prozac
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.
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.

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00986310

Locations
United States, California
University of California, Davis
Sacramento, California, United States, 95817
Sponsors and Collaborators
University of California, Davis
Citizens United for Research in Epilepsy (CURE)
Investigators
Principal Investigator: Lisa M Bateman, MD, FRCPC University of California, Davis
  More Information

No publications provided

Responsible Party: Lisa M. Bateman, MD, Principal Investigator, University of California, Davis
ClinicalTrials.gov Identifier: NCT00986310     History of Changes
Other Study ID Numbers: 200917358
Study First Received: September 25, 2009
Last Updated: November 2, 2012
Health Authority: United States: Institutional Review Board

Keywords provided by University of California, Davis:
fluoxetine
epilepsy
Prozac

Additional relevant MeSH terms:
Epilepsy
Epilepsies, Partial
Hypoventilation
Respiratory Insufficiency
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Respiration Disorders
Respiratory Tract Diseases
Signs and Symptoms, Respiratory
Signs and Symptoms
Fluoxetine
Serotonin Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Serotonin Agents
Physiological Effects of Drugs
Antidepressive Agents, Second-Generation
Antidepressive Agents
Psychotropic Drugs
Central Nervous System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on September 18, 2014