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

• Sponsor: University of California, Davis (Other)
• Overall Status: Completed
• CT.gov ID: NCT00986310
• Collaborator: (none)
• Enrollment: 2
• Location: 1
• Arms: 2
• Duration (Months): 34
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

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 or Disease	Intervention/Treatment	Phase
Uncontrolled Partial Epilepsy; Ictal Hypoventilation	Drug: Fluoxetine; Drug: Placebo	N/A

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 2 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Supportive Care
• Official Title: Efficacy of Fluoxetine in Reducing Ictal Hypoventilation in Patients With Partial Epilepsy
• Study Start Date: Aug 1, 2009
• Actual Primary Completion Date: Feb 1, 2012
• Actual Study Completion Date: Jun 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
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 Names: 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.

Outcome Measures

Primary Outcome Measures

1. 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. [6 weeks]

Secondary Outcome Measures

1. 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. [6 weeks]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Locations

	Site	City	State	Country	Postal Code
1	University of California, Davis	Sacramento	California	United States	95817

Sponsors and Collaborators

• University of California, Davis

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: University of California, Davis
• ClinicalTrials.gov Identifier: NCT00986310
• Other Study ID Numbers: 244486
• First Posted: Sep 29, 2009
• Last Update Posted: Nov 27, 2019
• Last Verified: Nov 1, 2019

• Keywords provided by University of California, Davis: fluoxetine; epilepsy; Prozac
• Additional relevant MeSH terms: Hypoventilation; Epilepsy; Epilepsies, Partial; Fluoxetine

Study Results

Participant Flow

Recruitment Details	The study was completed and the PI has left the institution without entering the results information. Efforts were made to contact the PI/study team members, but were unsuccessful. No study data are available.

Arm/Group Title	Fluoxetine	Placebo
Arm/Group Description	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. 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.	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. 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.
Period Title: Overall Study
STARTED	0	0
COMPLETED	0	0
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Fluoxetine	Placebo	Total
Arm/Group Description	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. 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.	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. 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.	Total of all reporting groups
Overall Participants	0	0	0
Age (years) []
Sex: Female, Male () []
Female
Male

Outcome Measures

1. Primary Outcome

Title	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

Outcome Measure Data

Analysis Population Description

The study was completed and the PI has left the institution without entering the results information. Efforts were made to contact the PI/study team members, but were unsuccessful. No study data are available.

Arm/Group Title	Fluoxetine	Placebo
Arm/Group Description	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. 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.	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. 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.
Measure Participants	0	0

2. Secondary Outcome

Title	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

Outcome Measure Data

Analysis Population Description

The study was completed and the PI has left the institution without entering the results information. Efforts were made to contact the PI/study team members, but were unsuccessful. No study data are available.

Arm/Group Title	Fluoxetine	Placebo
Arm/Group Description	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. 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.	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. 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.
Measure Participants	0	0

Adverse Events

Time Frame	The study was completed and the PI has left the institution without entering the results information. Efforts were made to contact the PI/study team members, but were unsuccessful. No study data are available.
Adverse Event Reporting Description	The study was completed and the PI has left the institution without entering the results information. Efforts were made to contact the PI/study team members, but were unsuccessful. No study data are available.
Arm/Group Title	Fluoxetine		Placebo
Arm/Group Description	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. 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.		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. 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.
All Cause Mortality
	Fluoxetine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		0/0 (NaN)
Serious Adverse Events
	Fluoxetine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		0/0 (NaN)
Other (Not Including Serious) Adverse Events
	Fluoxetine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		0/0 (NaN)

Limitations/Caveats

PI has left institution. Despite many attempts to contact, no response was received and results were not able to obtained nor entered.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.