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Randomized Controlled Trial of Hippocampal Stimulation for Temporal Lobe Epilepsy (METTLE)
This study is currently recruiting participants.
Verified by University of Calgary, September 2008
First Received: July 15, 2008   Last Updated: October 1, 2008   History of Changes
Sponsors and Collaborators: University of Calgary
University of Western Ontario, Canada
University of Toronto
Dalhousie University
University of Alberta
Information provided by: University of Calgary
ClinicalTrials.gov Identifier: NCT00717431
  Purpose

Our 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), or treating with medical therapy alone (MT), 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, and in HS-HI combined vs. MT. There are three treatment arms: 1) Hippocampal Electrode Implantation with Stimulation (HS). 2) Hippocampal Electrode Implantation without stimulation (HI). 3) Optimum Medical Therapy (MT) alone. We expect to demonstrate that HS is safe and superior to HI and MT in controlling seizures in patients with MTLE.


Condition Intervention Phase
Temporal Lobe Epilepsy
Procedure: Hippocampal Electrical Stimulation
Phase III

Genetics Home Reference related topics: autosomal dominant partial epilepsy with auditory features pyridoxal 5'-phosphate-dependent epilepsy pyridoxine-dependent epilepsy
MedlinePlus related topics: Epilepsy Seizures
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Active Control, Parallel Assignment, Safety/Efficacy Study
Official Title: Randomized Controlled Trial of Hippocampal Stimulation for Temporal Lobe Epilepsy

Further study details as provided by University of Calgary:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • Cognitive function: Change in mean scores from baseline to end of study. [ Time Frame: Months 1-7 ] [ Designated as safety issue: No ]

Estimated Enrollment: 90
Study Start Date: January 2008
Estimated Study Completion Date: August 2011
Estimated Primary Completion Date: January 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
2: Experimental
Hippocampal Implantation (Stimulator is OFF)
Procedure: Hippocampal Electrical Stimulation
Surgical Implantation of electrode and stimulator
3: Experimental
Hippocampal Stimulation (Stimulator is turned ON) Surgical Intervention
Procedure: Hippocampal Electrical Stimulation
Surgical Implantation of electrode and stimulator
1. Medical Therapy: No Intervention
These patients continue with their anti-epileptic medication only.

Detailed Description:

This is a multicentre, parallel-group, three-arm, 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 1:1:1 ratio into medical therapy only (MT), 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. Our study design and analysis allows for two co-primary hypotheses. Thus: In patients with MTLE, over a 6-month period, a) Is continuous HS plus medical therapy (MT) more efficacious than hippocampal implantation (HI) plus MT in reducing seizure frequency? and b) Is there a difference between any form of hippocampal intervention (HS or HI) and medical MT alone 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 and amount of interictal hippocampal spikes on depth electrode recordings?
  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Unilateral or Bilateral Mesial Temporal lobe Epilepsy (see 2.5.3. screening process).
  • Age ≥ 18 and ≤60 years.
  • Global IQ ≥70.
  • Failure of ≥ 2 AEDs approved for treatment of partial seizures, used alone or in combination at recommended dosages.
  • Average ≥ 2 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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00717431

Contacts
Contact: Kim Ford 403-944-4556 kim.ford@calgaryhealthregion.ca
Contact: Lisa Anderson, MSc 403-210-6372 lisamaria.anderson@calgaryhealthregion.ca

Locations
Canada, Alberta
Foothills Medical Centre, Clinical Neurosciences Recruiting
Calgary, Alberta, Canada
Contact: Kim Ford     403-944-4556     kim.ford@calgaryhealthregion.ca    
Contact: Lisa Anderson, MSc     403-210-6372     lisamaria.anderson@calgaryhealthregion.ca    
Principal Investigator: Samuel Wiebe, MD            
Sponsors and Collaborators
University of Calgary
University of Western Ontario, Canada
University of Toronto
Dalhousie University
University of Alberta
Investigators
Principal Investigator: Samuel Wiebe, MD University of Calgary
  More Information

No publications provided

Responsible Party: Foothills Medical Centre, Dept. Clinical Neurosciences ( Samuel Wiebe MD, MSc, FRCPC )
Study ID Numbers: 20492
Study First Received: July 15, 2008
Last Updated: October 1, 2008
ClinicalTrials.gov Identifier: NCT00717431     History of Changes
Health Authority: Canada: Health Canada

Keywords provided by University of Calgary:
Deep Brain Stimulation
Seizures
Epilepsy

Study placed in the following topic categories:
Epilepsies, Partial
Epilepsy
Seizures
Central Nervous System Diseases
Brain Diseases
Epilepsy, Temporal Lobe

Additional relevant MeSH terms:
Epilepsies, Partial
Epilepsy
Nervous System Diseases
Central Nervous System Diseases
Brain Diseases
Epilepsy, Temporal Lobe

ClinicalTrials.gov processed this record on May 07, 2009