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

Medical vs Electrical Therapy for Temporal Lobe Epilepsy

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.

Study Overview

• Status: Terminated
• Conditions: Temporal Lobe Epilepsy
• Intervention / Treatment: Procedure: Hippocampal Electrical Stimulation

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:

1. Is HS safe?
2. What is the effect of HS on cognition, mood, and quality of life?
3. What is the effect of HS on psychiatric morbidity?
4. Is the efficacy of HS associated with the presence, location and amount of interictal hippocampal spikes on depth electrode recordings?

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada
      • Foothills Medical Centre, Clinical Neurosciences

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Hippocampal Stimulation; Hippocampal Stimulation (Stimulator is turned ON) Surgical Intervention	Procedure: Hippocampal Electrical Stimulation; Surgical Implantation of electrode and stimulator
SHAM_COMPARATOR: Hippocampal Implantation; Hippocampal Implantation (Stimulator is turned OFF)Surgical Intervention	Procedure: Hippocampal Electrical Stimulation; Surgical Implantation of electrode and stimulator

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Rate of complex partial seizures (with or without secondary generalization) per person-month over 6 months of follow-up.	Months 1-7

Secondary Outcome Measures

Outcome Measure	Time Frame
Cognitive function: Change in mean scores from baseline to end of study.	Months 1-7

Collaborators and Investigators

• Sponsor: University of Calgary
• Collaborators: University of Alberta; University of Toronto; University of Western Ontario, Canada; Dalhousie University
• Investigators: Principal Investigator: Samuel Wiebe, MD, University of Calgary

Study record dates

Study Major Dates

• Study Start: January 1, 2008
• Primary Completion (ACTUAL): March 1, 2012
• Study Completion (ACTUAL): March 1, 2012

Study Registration Dates

• First Submitted: July 15, 2008
• First Submitted That Met QC Criteria: July 15, 2008
• First Posted (ESTIMATE): July 17, 2008

Study Record Updates

• Last Update Posted (ESTIMATE): April 2, 2012
• Last Update Submitted That Met QC Criteria: March 28, 2012
• Last Verified: March 1, 2012

More Information

Terms related to this study

• Keywords: Epilepsy; Deep Brain Stimulation; Seizures
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Epileptic Syndromes; Epilepsies, Partial; Epilepsy; Epilepsy, Temporal Lobe
• Other Study ID Numbers: 20492