Radiosurgery or Open Surgery for Epilepsy Trial (ROSE)

Study Description

Go to 

Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

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.

Condition or disease	Intervention/treatment	Phase
Epilepsy	Procedure: radiosurgery; Procedure: temporal lobectomy	Phase 3

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.

Study Design

Go to 

Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	61 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose:	Treatment
Official Title:	Radiosurgery Versus Lobectomy for Temporal Lobe Epilepsy
Study Start Date :	September 2009
Estimated Primary Completion Date :	July 2016
Estimated Study Completion Date :	July 2016

Arms and Interventions

Go to 

Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Arm	Intervention/treatment
Experimental: radiosurgery; Radiosurgical treatment of the medial temporal lobe	Procedure: radiosurgery; The stereotaxic frame will be secured to the skull with four pins. Patients will be taken to the MRI unit and receive a stereotaxic MRI. MRI data will be transferred to the Gamma Knife computer. Each patient will receive radiation to the mesial temporal lobe during a single treatment session. The amygdala and anterior 2cm of the hippocampus as well as the immediately adjacent parahippocampal gyrus will be included in the radiosurgical target. Patients will receive 24Gy to the 50% isodose line using an unlimited number of isocenters. The brainstem and optic nerve plus chiasm will receive less than 10 Gy and 8 Gy, respectively. After treatment, the stereotaxic frame will be removed from the patient's head.; Other Name: Gamma Knife
Active Comparator: temporal lobectomy; Resection of medial temporal lobe	Procedure: temporal lobectomy; The temporal lobectomy will be performed under general anesthesia. The superior temporal gyrus will be resected to a minimal degree (typically between 1 and 2cm) and the middle and inferior temporal gyri will be resected to approximately 3cm.The minimum amount of lateral temporal cortex required to perform an aggressive resection of medial temporal structures will be performed. The temporal portion of the amygdala and the anterior two to three cm of the hippocampus will be resected. In addition, nearby entorhinal cortex will be removed.

Outcome Measures

Go to 

Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :

1. 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. [ Time Frame: 3 years ]

Secondary Outcome Measures :

1. 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. [ Time Frame: 4 years ]

Eligibility Criteria

Go to 

Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Ages Eligible for Study:	18 Years and older (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

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.

Contacts and Locations

Go to 

Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Locations

United States, Alabama
University of Alabama at Birmingham
Birmingham, Alabama, United States, 35294
United States, California
University of California, San Diego
La Jolla, California, United States, 92037
University of Southern California
Los Angeles, California, United States, 90033
University of California, San Francisco
San Francisco, California, United States, 94143
United States, Indiana
Indiana University
Indianapolis, Indiana, United States, 46202
United States, Kentucky
University of Kentucky
Lexington, Kentucky, United States, 40536
United States, Minnesota
University of Minnesota
Minneapolis, Minnesota, United States, 55455
United States, New York
Columbia University
New York, New York, United States, 10032
State University of New York, Upstate Medical Center
Syracuse, New York, United States, 13210
United States, Pennsylvania
University of Pittsburgh
Pittsburgh, Pennsylvania, United States, 15213
United States, Virginia
University of Virginia
Charlottesville, Virginia, United States, 22908
United States, Washington
University of Washington
Seattle, Washington, United States, 98104
United States, West Virginia
West Virginia University
Morgantown, West Virginia, United States, 26508
India
All India Institute of Medical Sciences (AIIMS)
New Delhi, India, 110 029

Sponsors and Collaborators

University of California, San Francisco

Investigators

Principal Investigator:	Lawrence Ver Hoef, MD	University of Alabama at Birmingham
Principal Investigator:	Guy McKhann, MD	Columbia University
Principal Investigator:	Vincenta Salanova, MD	Indiana University
Principal Investigator:	Thomas Pittman, MD	University of Kentucky
Principal Investigator:	Andriana E. Palade, MD	West Virginia University
Principal Investigator:	Aviva Abosch, MD, PhD	University of Minnesota - Clinical and Translational Science Institute
Principal Investigator:	Anto Bagic, MD, MSc	University of Pittsburgh, Medical School
Principal Investigator:	Robert L Beach, MD, PhD	Upstate Medical University
Principal Investigator:	Evelyn S Tecoma, MD, PhD	University of California, San Diego
Principal Investigator:	Christi N Heck, MD, PhD	University of Southern California
Principal Investigator:	John W Miller, MD, PhD	University of Washington
Principal Investigator:	Nathan B Fountain, MD	University of Virginia
Principal Investigator:	Paul Garcia, MD	University of California, San Francisco
Principal Investigator:	Nicholas M. Barbaro, MD	University of California, San Francisco
Principal Investigator:	Mark S Quigg, MD, MSc	University of Virginia
Study Chair:	Kenneth D Laxer, MD	California Pacific Medical Center
Study Chair:	John Langfitt, MA, PhD	University of Rochester
Study Chair:	Penny Sneed, MD	University of California, San Francisco
Study Chair:	Michael W McDermott, MD	University of California, San Francisco

More Information

Go to 

Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Publications:

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.

Responsible Party:	University of California, San Francisco
ClinicalTrials.gov Identifier:	NCT00860145 History of Changes
Other Study ID Numbers:	U01NS058634 ( U.S. NIH Grant/Contract ); CRC; NINDS
First Posted:	March 12, 2009
Last Update Posted:	May 16, 2016
Last Verified:	May 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:	Yes
Plan Description:	Preliminary report 12/2016 at the American Epilepsy Society meeting. Full paper to follow.

Keywords provided by University of California, San Francisco:

epilepsy; radiosurgery; temporal lobectomy

Additional relevant MeSH terms:

Epilepsy; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases