Early Surgical Intervention to Treat Epilepsy

NCT ID: NCT00040326

Last Updated: 2010-02-23

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 200 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2002-07-31
• Study Completion Date: 2007-11-30

Brief Summary

The purpose of this trial is to compare the effectiveness of early surgical intervention for mesial temporal lobe epilepsy to continued treatment with antiepileptic drugs.

Detailed Description

Mesial temporal lobe epilepsy (MTLE) is the most common form of epilepsy, and the most medically intractable. An estimated one-quarter to one-half of the 400,000 patients in the United States with intractable epilepsy have MTLE. Generally, MTLE becomes intractable in adolescence and early adulthood. Persistence of seizures during this time commonly causes adverse social and psychological consequences which can become irreversible.

The current treatment of MTLE primarily consists of medications to control seizures. Usually surgical treatment is considered only if medications are not effective. Recent studies have shown that surgery can stop disabling seizures in 60 to 70% of patients with long standing MTLE. However, to date, no research study has examined surgery performed as an early therapy.

The goal of the study is to determine if more patients treated with early surgery become seizure free and have improved quality of life compared to similar patients who continue to receive antiepileptic medication only. This study will determine the difference in seizure frequency between the two groups and the impact of the two treatments on the quality of life of the participants.

Conditions

Epilepsy; Epilepsy, Temporal Lobe; Seizures

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

1

anteromesial temporal resection

Group Type: ACTIVE_COMPARATOR

anteromesial temporal resection

Intervention Type: PROCEDURE

surgical treatment for epilepsy

2

antiepileptic drugs

Group Type: ACTIVE_COMPARATOR

antiepileptic drugs

Intervention Type: DRUG

pharmacotherapy

Interventions

anteromesial temporal resection

surgical treatment for epilepsy

Intervention Type: PROCEDURE

antiepileptic drugs

pharmacotherapy

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Intractability: Two AEDs, one of which was either Dilantin, Tegretol, Carbatrol, or Trileptal used in appropriate doses, have failed due to inefficacy, not intolerance.
• Frequency and Duration: Persistence of disabling seizures at 6 per year or greater for less than two years after onset, or after recurrence if initial treatment resulted in seizure freedom for 6 or more months.
• Age: 12 years or older at baseline visit.
• History: Simple and complex partial seizures, with or without secondarily generalized seizures beginning in childhood or later, with or without febrile convulsions earlier.
• Absence of a history of serious cerebral insult after the age of 5; a progressive neurological disorder; mental retardation (I.Q. less than 70); psychogenic seizures; focal neurological deficits other than memory disturbances; unequivocal focal extratemporal EEG slowing or interictal spikes; or lesions on neuroimaging outside of the mesial temporal area.
• Seizure semiology: Auras that occur in isolation and are not primary sensory other than olfactory or gustatory. Absence of initial focal motor movements other than automatisms or dystonic posturing. Presence of postictal confusion.
• Neurological examination: No unexplained focal or lateralized neurological deficits other than memory dysfunction.
• Baseline QOL and ancillary outcome data:
• Adolescents - QOLIE-48-AD, CHQ, CBCL, PANAS, Life Events Scale, FAC, FEICS-PC completed.
• Adults - QOLIE-82/ESI55, locus of control, PANAS, Life Events Scale, FAD, FEICS-PC completed.
• Global rating scale completed.
• Baseline ancillary outcomes completed. Psychiatric evaluation: No evidence of psychosis, current or recent substance abuse, suicidality, anorexia, or psychogenic seizures. Baseline BSI and MINI or KSADS completed.
• Neuropsychological testing: I.Q. of greater than 70. No significant focal neurocognitive dysfunction inconsistent with MRI and PET findings. Baseline neuropsychological testing completed.
• Neuroimaging: Hippocampal atrophy on MRI T1 imaging with either increased ipsilateral mesial signal on T2 imaging, or ipsilateral hypometabolism on PET (Class I), or either hippocampal atrophy on MRI only, or temporal hypometabolism on PET only (Class II).
• Absence of temporal neocortical or extratemporal lesions on MRI, or diffuse unilateral or bilateral hypometabolism on PET.
• Video-EEG Monitoring:
• If neuroimaging is Class I, ictal EEG onset is lateralized to the ipsilateral side; if neuroimaging is Class II, ictal EEG onset is focal on the ipsilateral side.
• Absence of contralateral or extratemporal ictal onset.
• Absence of persistent extratemporal, or predominant contralateral focal interictal spikes or slowing, or generalized interictal spikes.
• Absence of psychogenic seizures.
• Seizure baseline: Seizure log, seizure report forms, and seizure severity scale completed.
• IAP: In those randomized to surgery only, contralateral hemisphere can support memory.

• Minimum Eligible Age: 12 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of California, Los Angeles

OTHER

Sponsor Role: lead

Responsible Party

UCLA School of Medicine, Department of Neurology

Principal Investigators

Jerome Engel, Jr., M.D., Ph.D.

Role: PRINCIPAL_INVESTIGATOR

UCLA School of Medicine, Department of Neurology

Locations

Barrow Neurological Institute

Phoenix, Arizona, United States

UCLA School of Medicine, Department of Neurology

Los Angeles, California, United States

Emory University

Atlanta, Georgia, United States

Northwestern University

Chicago, Illinois, United States

Johns Hopkins University

Baltimore, Maryland, United States

University of Michigan, Department of Neurology

Ann Arbor, Michigan, United States

University of Rochester, Department of Neurology

Rochester, New York, United States

Cleveland Clinic

Cleveland, Ohio, United States

Thomas Jefferson University Hospital

Philadelphia, Pennsylvania, United States

Vanderbilt University

Nashville, Tennessee, United States

University of Virginia

Charlottesville, Virginia, United States

Swedish Medical Center

Seattle, Washington, United States

Countries

United States

References

Engel J Jr, McDermott MP, Wiebe S, Langfitt JT, Stern JM, Dewar S, Sperling MR, Gardiner I, Erba G, Fried I, Jacobs M, Vinters HV, Mintzer S, Kieburtz K; Early Randomized Surgical Epilepsy Trial (ERSET) Study Group. Early surgical therapy for drug-resistant temporal lobe epilepsy: a randomized trial. JAMA. 2012 Mar 7;307(9):922-30. doi: 10.1001/jama.2012.220.

Reference Type: DERIVED

PMID: 22396514 (View on PubMed)

Other Identifiers

R01NS42372

Identifier Type: -

Identifier Source: org_study_id