Radiosurgery or Open Surgery for Epilepsy Trial

NCT00860145 | Completed DMC

• 3 other identifiers: U01NS058634CRCNINDS
• Study Type: interventional
• Target: 61
• Locations: 2 countries
• Sites: 14

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.

Conditions

Epilepsy

Keywords

epilepsy; radiosurgery; temporal lobectomy

Outcome Measures

Primary Outcomes (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.

  3 years

Secondary Outcomes (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.

  4 years

Study Arms (2)

radiosurgery

EXPERIMENTAL

Radiosurgical treatment of the medial temporal lobe

Procedure: radiosurgery

temporal lobectomy

ACTIVE COMPARATOR

Resection of medial temporal lobe

Procedure: temporal lobectomy

Interventions

radiosurgery PROCEDURE

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.

Also known as: Gamma Knife

radiosurgery

temporal lobectomy PROCEDURE

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.

temporal lobectomy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may not qualify if:

• 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.
• Seizure type: Patients must have simple and/or complex partial seizures with or without secondary generalization.
• 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).
• 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.
• Subjects should be on stable doses of antiepileptic medications for at least 3 months prior to treatment.
• 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.
• 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.
• 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.
• Patients with radiographic evidence of other pathologies such as vascular malformations or tumors will be excluded.
• Patients with diabetes mellitus or hypertension will be excluded from this study because radiation injury to the brain is more common in these patients.
• 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.
• 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.
• Patients with any progressive neurological disorder (such as multiple sclerosis or systemic lupus erythematosis) are excluded.
• Patients with a history of poor compliance with past antiepileptic drug therapy as judged by the principal investigator are excluded.
• Patients with a recent history of abusing drugs or alcohol with significance as judged by the principal investigator are excluded.

Sponsors & Collaborators

• University of California, San Francisco: lead

Study Sites (14)

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

Location

University of California, San Diego

La Jolla, California, 92037, United States

Location

University of Southern California

Los Angeles, California, 90033, United States

Location

University of California, San Francisco

San Francisco, California, 94143, United States

Location

Indiana University

Indianapolis, Indiana, 46202, United States

Location

University of Kentucky

Lexington, Kentucky, 40536, United States

Location

University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

Columbia University

New York, New York, 10032, United States

Location

State University of New York, Upstate Medical Center

Syracuse, New York, 13210, United States

Location

University of Pittsburgh

Pittsburgh, Pennsylvania, 15213, United States

Location

University of Virginia

Charlottesville, Virginia, 22908, United States

Location

University of Washington

Seattle, Washington, 98104, United States

Location

West Virginia University

Morgantown, West Virginia, 26508, United States

Location

All India Institute of Medical Sciences (AIIMS)

New Delhi, 110 029, India

Location

Related Publications (1)

• 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.

  PMID: 19243009 BACKGROUND

MeSH Terms

Conditions

Epilepsy

Interventions

Radiosurgery; Anterior Temporal Lobectomy

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• 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

  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

  PRINCIPAL INVESTIGATOR

• 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

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 11, 2009
• First Posted: March 12, 2009
• Study Start: September 1, 2009
• Primary Completion: June 1, 2016
• Study Completion: July 1, 2016
• Last Updated: May 14, 2018

Record last verified: 2018-05

Data Sharing

• IPD Sharing: Will share

Locations

US (13); IN (1)