E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Mesial Temporal Lobe Epilepsy |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10043209 |
E.1.2 | Term | Temporal lobe epilepsy |
E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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. |
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E.2.2 | Secondary objectives of the trial |
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 |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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)
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E.4 | Principal 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.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary outcome measure for this study is the measure of verbal and spatial learning |
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E.5.1.1 | 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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E.5.2 | Secondary end point(s) |
Secondary endpoints for this trial are:
- Pattern separation measures - Brain MRI microstructure - seizure frequency |
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E.5.2.1 | 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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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | No |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 11 |
E.8.9.1 | In the Member State concerned days | 31 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 11 |
E.8.9.2 | In all countries concerned by the trial days | 31 |