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

This study has been terminated.
(insufficient enrolment)
Sponsor:
Collaborators:
University of Western Ontario, Canada
University of Toronto
Dalhousie University
University of Alberta
Information provided by (Responsible Party):
Dr. Sam Wiebe, University of Calgary
ClinicalTrials.gov Identifier:
NCT00717431
First received: July 15, 2008
Last updated: March 28, 2012
Last verified: March 2012

July 15, 2008
March 28, 2012
January 2008
March 2012   (final data collection date for primary outcome measure)
Rate of complex partial seizures (with or without secondary generalization) per person-month over 6 months of follow-up. [ Time Frame: Months 1-7 ] [ Designated as safety issue: No ]
Same as current
Complete list of historical versions of study NCT00717431 on ClinicalTrials.gov Archive Site
Cognitive function: Change in mean scores from baseline to end of study. [ Time Frame: Months 1-7 ] [ Designated as safety issue: No ]
Same as current
Not Provided
Not Provided
 
A Multicenter Study of Hippocampal Electrical Stimulation (HS, in Mesial Temporal Lobe Epilepsy
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.

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?
Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Temporal Lobe Epilepsy
Procedure: Hippocampal Electrical Stimulation
Surgical Implantation of electrode and stimulator
  • Experimental: Hippocampal Stimulation
    Hippocampal Stimulation (Stimulator is turned ON) Surgical Intervention
    Intervention: Procedure: Hippocampal Electrical Stimulation
  • Sham Comparator: Hippocampal Implantation
    Hippocampal Implantation (Stimulator is turned OFF)Surgical Intervention
    Intervention: Procedure: Hippocampal Electrical Stimulation
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Terminated
8
March 2012
March 2012   (final data collection date for primary outcome measure)

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.
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
Canada
 
NCT00717431
20492
Yes
Dr. Sam Wiebe, University of Calgary
University of Calgary
  • University of Western Ontario, Canada
  • University of Toronto
  • Dalhousie University
  • University of Alberta
Principal Investigator: Samuel Wiebe, MD University of Calgary
University of Calgary
March 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP