Clinical trial NCT00860145: Radiosurgery or Open Surgery for Epilepsy Trial
Official title: Radiosurgery Versus Lobectomy for Temporal Lobe Epilepsy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Epilepsy
Keywords: epilepsy
radiosurgery
temporal lobectomy
Lead sponsor: University of California, San Francisco
Sponsor class: OTHER
First posted: 2009-03-12
Enrollment: 61
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study will compare radiosurgery (focused radiation, Gamma Knife Radiosurgery) with temporal lobectomy (standard surgical care) as a treatment of temporal lobe epilepsy. Patients who have seizures that begin in their temporal lobe that are not controlled with medications into the trial will be offered entry. Patients with a high likelihood of having their seizures controlled with open surgery will have treatment randomized between the standard surgery and radiosurgery. A prior study has shown that focused radiation (radiosurgery) may also reduce or eliminate seizures arising from the temporal lobe. The main study hypothesis is that radiosurgery is as safe and effective as temporal lobectomy in treating patients with seizures arising from the medial temporal lobe.

Detailed description: The purpose of this study is to compare the effectiveness of Gamma Knife radiosurgery with temporal lobectomy in the treatment of patients with drug resistant temporal lobe epilepsy. Aim 1 is designed to compare the seizure-free outcomes and morbidity of radiosurgery for patients with drug resistant temporal lobe epilepsy with those of open temporal lobectomy. Our primary hypothesis is that radiosurgery will be non-inferior to lobectomy with respect to seizure-free rates at 25-36 months following therapy (one-year of seizure freedom beginning 2 years after treatment).

Aim 2 is designed to compare the neuropsychological outcomes in patients undergoing radiosurgery and temporal lobe surgery, in particular with respect to verbal memory function for language-dominant hemisphere treated patients. Our hypothesis is that patients treated for speech-dominant temporal lobe seizures with temporal lobectomy will show greater reduction in verbal memory than patients treated with radiosurgery.

Aim 3 is designed to determine what changes occur in the quality of life of patients with temporal lobe epilepsy following radiosurgical treatment as compared with open surgery. Our primary hypothesis is that there will be improvements (comparing baseline with 3 years post-treatment) in quality of life measures in both groups. Our secondary hypothesis is that both open surgery and radiosurgery subjects will undergo transient reductions in quality of life measures caused by treatment effects during the first year following treatment, but that quality of life will improve for subjects who become seizure-free, independent of treatment group.

Aim 4 is designed to compare the cost-effectiveness of radiosurgery compared with open surgery. Specifically, the marginal cost-utility ratio will fall below $50,000/QALY, a threshold thought to indicate that outcomes are considered worth the cost.

Eligibility criteria: Inclusion and Exclusion Criteria:

Adults (18 years and older) of either gender who would otherwise be eligible for temporal lobe resection will be offered enrollment for randomization to RS or ATL.

1. Seizure type: Patients must have simple and/or complex partial seizures with or without secondary generalization.
2. Seizure Frequency: Patients must have at least 3 complex partial seizures during the 3 month (12 week) baseline seizure diary period with at least 1 of 3 seizures occurring within the last 2 months (8 weeks).
3. Patients with electrographic evidence of seizures arising from one temporal lobe, with radiographic evidence of mesial temporal sclerosis in the same temporal lobe will be included. Patients with normal MRIs, bilateral hippocampal damage, or cortical lesion will be excluded.
4. Subjects should be on stable doses of antiepileptic medications for at least 3 months prior to treatment.
5. All female patients of childbearing age will have documented that they are using a safe and effective means of birth control and will have a negative urine pregnancy test completed within 1 week prior to their treatment.
6. Patients should be able to understand the potential benefits and risks of this therapy and be able to understand the protocol and sign their own consent forms. For these reasons, only patients 18 years and older and with I.Q. greater than or equal to 70 will be included.
7. Patients with any focal neurologic deficit that would make it difficult to detect a new radiation-associated injury will be excluded. All patients will receive formal visual field testing (Humphrey) and patients with visual field deficits will be excluded.
8. Patients with radiographic evidence of other pathologies such as vascular malformations or tumors will be excluded.
9. Patients with diabetes mellitus or hypertension will be excluded from this study because radiation injury to the brain is more common in these patients.
10. Subjects should not have significant psychiatric conditions that would make accurate assessment of seizure frequency difficult, as judged by the principal investigator. Such conditions include a history of non-epileptic seizures, psychosis (other than post-ictal psychosis) and severe mood disorders including suicide attempt within past 12 months or noncompliance with psychotropic medications.
11. Patients with a history of significant past or present medical disorders determined severe enough to prevent participation in a surgical trial by the principal investigator are excluded.
12. Patients with any progressive neurological disorder (such as multiple sclerosis or systemic lupus erythematosis) are excluded.
13. Patients with a history of poor compliance with past antiepileptic drug therapy as judged by the principal investigator are excluded.
14. Patients with a recent history of abusing drugs or alcohol with significance as judged by the principal investigator are excluded.
15. Patients who are receiving any investigational drugs at the time of enrollment are excluded.
16. Patients with current use of vigabatrin are excluded. Past use does not exclude a patient pending a normal formal visual field test.
17. Patients with currently functioning vagal nerve stimulators (VNS) are excluded. Past use does not exclude a patient as long as the device is explanted. Indwelling VNS electrodes are permitted in agreement with each center's policies on brain MRI imaging.
18. Patients who can not be anticipated to participate for the full 36 months of the trial will be excluded.
19. Native English speakers from the U.S. or other English speaking countries or patients who learned English before age 5 and were educated in English. Spanish speaking patients can be included as long as the study site can provide an officially translated (IRB approved) consent form in Spanish. Non-Spanish speaking patients with English as a second language (ESL) and/or non-English and non-Spanish speaking patients can be included only under the following conditions: 1) the study site must be able to have the consent form translated into the patient's native language using an official translator, and 2) the study site's neuropsychologist must be willing and able to assess the patient at baseline and post-treatment at 12, 24, and 36 months in that patient's native language to ensure the patient's safety.

Primary outcomes:
measure: The primary outcome measure is freedom from seizures. The primary goal of Specific Aim 1 is to demonstrate that the 3-year seizure-free rate of radiosurgery is not inferior to that of temporal lobectomy between 24 and 36 months following treatment.
timeFrame: 3 years
Secondary outcomes:
measure: Specific Aim 2 is designed to show that patients treated for speech-dominant temporal lobe seizures with temporal lobectomy will show greater reduction in verbal memory than patients treated with radiosurgery.
timeFrame: 4 years
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: La Jolla
country: United States
facility: University of California, San Diego
state: California
city: Los Angeles
country: United States
facility: University of Southern California
state: California
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
city: Indianapolis
country: United States
facility: Indiana University
state: Indiana
city: Lexington
country: United States
facility: University of Kentucky
state: Kentucky
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: New York
country: United States
facility: Columbia University
state: New York
city: Syracuse
country: United States
facility: State University of New York, Upstate Medical Center
state: New York
city: Pittsburgh
country: United States
facility: University of Pittsburgh
state: Pennsylvania
city: Charlottesville
country: United States
facility: University of Virginia
state: Virginia
city: Seattle
country: United States
facility: University of Washington
state: Washington
city: Morgantown
country: United States
facility: West Virginia University
state: West Virginia
city: New Delhi
country: India
facility: All India Institute of Medical Sciences (AIIMS)
Study officials:
affiliation: University of Alabama at Birmingham
name: Lawrence Ver Hoef, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Columbia University
name: Guy McKhann, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Indiana University
name: Vincenta Salanova, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Kentucky
name: Thomas Pittman, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: West Virginia University
name: Andriana E. Palade, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Minnesota
name: Aviva Abosch, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Pittsburgh, Medical School
name: Anto Bagic, MD, MSc
role: PRINCIPAL_INVESTIGATOR
affiliation: Upstate Medical University
name: Robert L Beach, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of California, San Diego
name: Evelyn S Tecoma, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Southern California
name: Christi N Heck, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Washington
name: John W Miller, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Virginia
name: Nathan B Fountain, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of California, San Francisco
name: Paul Garcia, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of California, San Francisco
name: Nicholas M. Barbaro, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Virginia
name: Mark S Quigg, MD, MSc
role: PRINCIPAL_INVESTIGATOR
affiliation: California Pacific Medical Center
name: Kenneth D Laxer, MD
role: STUDY_CHAIR
affiliation: University of Rochester
name: John Langfitt, MA, PhD
role: STUDY_CHAIR
affiliation: University of California, San Francisco
name: Penny Sneed, MD
role: STUDY_CHAIR
affiliation: University of California, San Francisco
name: Michael W McDermott, MD
role: STUDY_CHAIR
References:
citation: Barbaro NM, Quigg M, Broshek DK, Ward MM, Lamborn KR, Laxer KD, Larson DA, Dillon W, Verhey L, Garcia P, Steiner L, Heck C, Kondziolka D, Beach R, Olivero W, Witt TC, Salanova V, Goodman R. A multicenter, prospective pilot study of gamma knife radiosurgery for mesial temporal lobe epilepsy: seizure response, adverse events, and verbal memory. Ann Neurol. 2009 Feb;65(2):167-75. doi: 10.1002/ana.21558.