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A Multicenter Study of Hippocampal Electrical Stimulation (HS, in Mesial Temporal Lobe Epilepsy (METTLE)

Primary Purpose

Temporal Lobe Epilepsy

Status

Terminated

Phase

Phase 3

Locations

Canada

Study Type

Interventional

Intervention

Hippocampal Electrical Stimulation

About this trial

This is an interventional treatment trial for Temporal Lobe Epilepsy focused on measuring Deep Brain Stimulation, Seizures, Epilepsy

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Unilateral or Bilateral Mesial Temporal lobe Epilepsy.
Age ≥ 18 years.
Global IQ ≥70.
Failure of ≥ 2 AEDs approved for treatment of partial seizures, used alone or in combination at recommended dosages.
Average ≥ 3 seizure-days per month in prior 6 months during which disabling seizures occurred. Disabling seizures are defined as complex partial seizures with or without secondary generalization, or as simple partial seizures that are noticeable by others or interfere with function.
Ability to complete self-administered questionnaires.
Availability of reliable collateral historian or witness.
Patient preference for non-resective surgery, or not a candidate for mesial temporal resection.
Give written informed consent.

Exclusion Criteria:

Extratemporal or multifocal epilepsy.
MRI evidence of potentially epileptogenic lesions outside the mesial temporal region.
Lesions precluding electrode implantation (eg, vascular malformations, vascular tumors).
Severe hippocampal sclerosis that in the surgeon's opinion precludes accurate electrode placement.
Brain lesions that demand prompt surgical therapy (eg, malignant tumors, vascular malformations).
Progressive neurological disorders (eg, malignant tumor, dementia, degenerative disorders).
Medical or psychiatric conditions precluding surgery or interfering with adherence to treatment and follow-up.
Planned pregnancy during the study. Women of child-bearing age will require a negative pregnancy test and adequate contraception methods.
Ongoing or planned participation in other studies of new epilepsy therapies.
Contraindication for stereotactic surgery, e.g. bleeding diathesis, anticoagulants, treatment with valproate at the time of surgery (risk of bleeding).
Any condition that would make participation in the trial detrimental to the patient's health.

Sites / Locations

Foothills Medical Centre, Clinical Neurosciences

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Sham Comparator

Arm Label

Hippocampal Stimulation

Hippocampal Implantation

Arm Description

Hippocampal Stimulation (Stimulator is turned ON) Surgical Intervention

Hippocampal Implantation (Stimulator is turned OFF)Surgical Intervention

Outcomes

Primary Outcome Measures

Rate of complex partial seizures (with or without secondary generalization) per person-month over 6 months of follow-up.

Secondary Outcome Measures

Cognitive function: Change in mean scores from baseline to end of study.

Full Information

NCT ID

NCT00717431

First Posted

July 15, 2008

Last Updated

March 28, 2012

Sponsor

University of Calgary

Collaborators

University of Western Ontario, Canada, University of Toronto, Dalhousie University, University of Alberta

1. Study Identification

Unique Protocol Identification Number

NCT00717431

Brief Title

A Multicenter Study of Hippocampal Electrical Stimulation (HS, in Mesial Temporal Lobe Epilepsy

Acronym

METTLE

Official Title

Medical vs Electrical Therapy for Temporal Lobe Epilepsy

Study Type

Interventional

2. Study Status

Record Verification Date

March 2012

Overall Recruitment Status

Terminated

Why Stopped

insufficient enrolment

Study Start Date

January 2008 (undefined)

Primary Completion Date

March 2012 (Actual)

Study Completion Date

March 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

University of Calgary

Collaborators

University of Western Ontario, Canada, University of Toronto, Dalhousie University, University of Alberta

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

The primary goal is to determine whether hippocampal electrical stimulation (HS) is safe and more effective than simply implanting an electrode in the hippocampus without electrical stimulation (HI), in patients with mesial temporal lobe epilepsy (MTLE). This will be assessed by the rate of complex partial seizures per person-month over 6 months of follow-up in HS vs. HI. There are two treatment arms: 1) Hippocampal Electrode Implantation with Stimulation (HS). 2) Hippocampal Electrode Implantation without stimulation (HI). The investigators expect to demonstrate that HS is safe and superior to HI in controlling seizures in patients with MTLE.

Detailed Description

This is a multicentre, parallel-group, double blind randomized controlled trial involving patients with MTLE who may be candidates for resective surgery or whose memory function precludes resective surgery. Eligible patients will be randomized in a 2:1 ratio into hippocampal electrode implantation with stimulation (HS), or hippocampal electrode implantation without stimulation (HI). Patients will be followed for seven months after randomization. One month will be devoted to adjustment of interventions, and 6 months to follow-up and outcome assessment. At the end of seven months, all patients will be offered the option of HS, electrode removal, surgical therapy or medical therapy, based on best evidence and patient preference. Primary Question: In patients with MTLE, over a 6-month period: Is continuous HS plus medical therapy (MT) more efficacious than hippocampal implantation (HI) plus MT in reducing seizure frequency? Secondary Questions: In patients with MTLE, over a 6-month period: Is HS safe? What is the effect of HS on cognition, mood, and quality of life? What is the effect of HS on psychiatric morbidity? Is the efficacy of HS associated with the presence, location and amount of interictal hippocampal spikes on depth electrode recordings?

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Temporal Lobe Epilepsy

Keywords

Deep Brain Stimulation, Seizures, Epilepsy

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

8 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Hippocampal Stimulation

Arm Type

Experimental

Arm Description

Hippocampal Stimulation (Stimulator is turned ON) Surgical Intervention

Arm Title

Hippocampal Implantation

Arm Type

Sham Comparator

Arm Description

Hippocampal Implantation (Stimulator is turned OFF)Surgical Intervention

Intervention Type

Procedure

Intervention Name(s)

Hippocampal Electrical Stimulation

Intervention Description

Surgical Implantation of electrode and stimulator

Primary Outcome Measure Information:

Title

Rate of complex partial seizures (with or without secondary generalization) per person-month over 6 months of follow-up.

Time Frame

Months 1-7

Secondary Outcome Measure Information:

Title

Cognitive function: Change in mean scores from baseline to end of study.

Time Frame

Months 1-7

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Unilateral or Bilateral Mesial Temporal lobe Epilepsy. Age ≥ 18 years. Global IQ ≥70. Failure of ≥ 2 AEDs approved for treatment of partial seizures, used alone or in combination at recommended dosages. Average ≥ 3 seizure-days per month in prior 6 months during which disabling seizures occurred. Disabling seizures are defined as complex partial seizures with or without secondary generalization, or as simple partial seizures that are noticeable by others or interfere with function. Ability to complete self-administered questionnaires. Availability of reliable collateral historian or witness. Patient preference for non-resective surgery, or not a candidate for mesial temporal resection. Give written informed consent. Exclusion Criteria: Extratemporal or multifocal epilepsy. MRI evidence of potentially epileptogenic lesions outside the mesial temporal region. Lesions precluding electrode implantation (eg, vascular malformations, vascular tumors). Severe hippocampal sclerosis that in the surgeon's opinion precludes accurate electrode placement. Brain lesions that demand prompt surgical therapy (eg, malignant tumors, vascular malformations). Progressive neurological disorders (eg, malignant tumor, dementia, degenerative disorders). Medical or psychiatric conditions precluding surgery or interfering with adherence to treatment and follow-up. Planned pregnancy during the study. Women of child-bearing age will require a negative pregnancy test and adequate contraception methods. Ongoing or planned participation in other studies of new epilepsy therapies. Contraindication for stereotactic surgery, e.g. bleeding diathesis, anticoagulants, treatment with valproate at the time of surgery (risk of bleeding). Any condition that would make participation in the trial detrimental to the patient's health.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Samuel Wiebe, MD

Organizational Affiliation

University of Calgary

Official's Role

Principal Investigator

Facility Information:

Facility Name

Foothills Medical Centre, Clinical Neurosciences

City

Calgary

State/Province

Alberta

Country

Canada

12. IPD Sharing Statement

Learn more about this trial

A Multicenter Study of Hippocampal Electrical Stimulation (HS, in Mesial Temporal Lobe Epilepsy

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