A clinical trial investigating the effect of the anti-depressant fluoxetine on learning and memory in people with epilepsy.

Conditions

Mesial Temporal Lobe Epilepsy MedDRA version: 18.0 Level: PT Classification code 10043209 Term: Temporal lobe epilepsy System Organ Class: 10029205 - Nervous system disorders

Cheney Drew, Mark Postans, Cateno Petralia, Rachel McNamara, Philip Pallmann et al. (11 authors)

Pilot and Feasibility Studies2019-07-061 citations

10.1186/s40814-019-0474-x

Interventions

Trade Name: fluoxetine Product Name: Fluoxetine Pharmaceutical Form: Capsule INN or Proposed INN: fluoxetine hydrochloride CAS Number: 5

Eligibility

Sex/Gender

All

Inclusion criteria

Inclusion criteria: The inclusion criteria for this trial are; • Adult patients between the ages of 18-65yrs Adult persons over the age of 65 will not be included as neurogenesis (the postulated biological target) diminishes significantly after this age and this subgroup therefore may not benefit. If benefit is shown under 65 then a subsequent study to assess benefit in this age group may be carried out. • diagnosis of mesial temporal lobe epilepsy • unilateral hippocampal sclerosis (confirmed by MRI) Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 60 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range 0

Exclusion criteria

Exclusion criteria: Exclusion Criteria for this trial are; • bilateral hippocampal sclerosis on MRI • presence of significant active depression and/ or anxiety as determined by HADS scoring (11 or above on either subscale) • Persons lacking capacity or an IQ score of 80 or below as assessed by the WASI • presence of poorly controlled seizures in patients undergoing active AED changes • any participant not suitable for MRI • pregnancy • Wishing to breast feed during the trial • participation in another clinical trial of an investigational medicinal product (IMP) • previous adverse reaction to fluoxetine • contraindicated concomitant medication – such as Monoamine Oxidase Inhibitors • hepatic impairment that would require any dose adjustment for fluoxetine (elevated liver Enzymes (- 2.5 or more times the upper limit of the normal range). • congenital long QT syndrome, a family history of QT prolongation or other clinical conditions that predispose to arrhythmias (e.g., hypokalemia, hypomagnesemia, bradycardia, acute myocardial infarction or uncompensated heart failure). An ECG will be performed in patients with a stable cardiac history. Most patients in our database have already been screeened for prolonged Q-T syndrome as part of their epilepsy evaluation. • Patients on Tamoxifen as concomitant Fluoxetine may lead to reduced concentrations of its active metabolite endoxifen. • Participants taking St John’s Wort should agree to discontinue it before taking the IMP. If not, they will be excluded, as St John’s Wort potentiates the serotonergic effects of Fluoxetine.

Design outcomes

Primary

Measure	Time frame
Secondary Objective: To determine the effect of oral treatment with fluoxetine on:; 1. verbal learning in patients with mesial temporal lobe epilepsy after a two month period of treatment. 2. spatial and/or verbal learning in patients with mesial temporal lobe epilepsy two months after treatment withdrawal. 3. spatial and/or verbal memory in patients with mesial temporal lobe epilepsy after a two month period of treatment. 4. spatial and/or verbal memory in patients with mesial temporal lobe epilepsy two months after treatment withdrawal. To determine whether: 5. patients differ in the severity of their learning deficit depending on which side the hippocampal sclerosis occurs 6. patients with TLE show deficits in pattern separation and if such deficits predict a response to fluoxetine 7. hippocampal microstructure correlates with allocentric learning and memory deficits and/or the response to fluoxetine 8. fluoxetine alters seizure freque ;Main Objective: To determine if treatment with oral fluoxetine can change spatial learning in patients with mesial temporal lobe epilepsy after a two month period of treatment.;Primary end point(s): The primary outcome measure for this study is the measure of verbal and spatial learning;Timepoint(s) of evaluation of this end point: This measure will be evaluated at baseline, 60 days after starting IMP treatment and again 60 days after IMP has been stopped.	—

Measure

Time frame

Secondary Objective: To determine the effect of oral treatment with fluoxetine on:; 1. verbal learning in patients with mesial temporal lobe epilepsy after a two month period of treatment. 2. spatial and/or verbal learning in patients with mesial temporal lobe epilepsy two months after treatment withdrawal. 3. spatial and/or verbal memory in patients with mesial temporal lobe epilepsy after a two month period of treatment. 4. spatial and/or verbal memory in patients with mesial temporal lobe epilepsy two months after treatment withdrawal. To determine whether: 5. patients differ in the severity of their learning deficit depending on which side the hippocampal sclerosis occurs 6. patients with TLE show deficits in pattern separation and if such deficits predict a response to fluoxetine 7. hippocampal microstructure correlates with allocentric learning and memory deficits and/or the response to fluoxetine 8. fluoxetine alters seizure freque ;Main Objective: To determine if treatment with oral fluoxetine can change spatial learning in patients with mesial temporal lobe epilepsy after a two month period of treatment.;Primary end point(s): The primary outcome measure for this study is the measure of verbal and spatial learning;Timepoint(s) of evaluation of this end point: This measure will be evaluated at baseline, 60 days after starting IMP treatment and again 60 days after IMP has been stopped.

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Secondary

Measure	Time frame
Secondary end point(s): Secondary endpoints for this trial are: - Pattern separation measures - Brain MRI microstructure - seizure frequency ; Timepoint(s) of evaluation of this end point: Pattern separation measures will be evaluated at baseline, 60 days after starting IMP treatment and 60 days after finishing IMP treatment. Brain MRI structure will be measured at baseline only Seizure frequency will be evaluated at each patient visit.	—

Measure

Time frame

Secondary end point(s): Secondary endpoints for this trial are: - Pattern separation measures - Brain MRI microstructure - seizure frequency ; Timepoint(s) of evaluation of this end point: Pattern separation measures will be evaluated at baseline, 60 days after starting IMP treatment and 60 days after finishing IMP treatment. Brain MRI structure will be measured at baseline only Seizure frequency will be evaluated at each patient visit.

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Countries

United Kingdom

Contacts

Public ContactCheney Drew

South East Wales Trial Unit

DrewC5@cardiff.ac.uk02920687295

Outcome results

None listed