EpilepsyROSENCT00860145
Radiosurgery or Open Surgery for Epilepsy Trial
A study testing radiosurgery and temporal lobectomy in people with Epilepsy, run by University of California, San Francisco at 14 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Epilepsy
- What is being tested?
- radiosurgery and temporal lobectomy
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 61 participants
- Where
- 14 sitesin 2 countries
- Study dates
- Sep 2009to 1 Jul 2016
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Show all 20Show fewer
- 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.
- Patients who are receiving any investigational drugs at the time of enrollment are excluded.
- Patients with current use of vigabatrin are excluded. Past use does not exclude a patient pending a normal formal visual field test.
- 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.
- Patients who can not be anticipated to participate for the full 36 months of the trial will be excluded.
- 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.
Who cannot join
None listed.
Trial locations and contacts
14 sites in 2 countries.
14 sites in 2 countries
United States13 sites
University of Alabama at Birmingham
Birmingham, Alabama, 35294
University of Virginia
Charlottesville, Virginia, 22908
Indiana University
Indianapolis, Indiana, 46202
University of California, San Diego
La Jolla, California, 92037
University of Kentucky
Lexington, Kentucky, 40536
University of Southern California
Los Angeles, California, 90033
University of Minnesota
Minneapolis, Minnesota, 55455
West Virginia University
Morgantown, West Virginia, 26508
Columbia University
New York, New York, 10032
University of Pittsburgh
Pittsburgh, Pennsylvania, 15213
University of California, San Francisco
San Francisco, California, 94143
University of Washington
Seattle, Washington, 98104
State University of New York, Upstate Medical Center
Syracuse, New York, 13210
About this study
Official title: Radiosurgery Versus Lobectomy for Temporal Lobe Epilepsy
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.
Read the 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.
- Conditions
- Epilepsy
- Being tested
- radiosurgery, temporal lobectomy
- Keywords
- epilepsy, radiosurgery, temporal lobectomy
- Medical subject headings
- Epilepsy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
radiosurgeryProcedure or surgery
Also called Gamma Knife
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.
temporal lobectomyProcedure or surgery
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.
| Study group | Role | What they receive |
|---|---|---|
| radiosurgery | Experimental | Radiosurgical treatment of the medial temporal lobe Receives: Procedure: radiosurgery |
| temporal lobectomy | Active comparator | Resection of medial temporal lobe Receives: Procedure: temporal lobectomy |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 4 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Mar 2009 (estimated)
- Study startSep 2009
- Primary completion1 Jun 2016
- Study completion1 Jul 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for EpilepsyStudies of the same condition, open and under way.
- More trials run by University of California, San FranciscoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 61 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, San Francisco
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Lawrence Ver Hoef, MD, Principal investigator, University of Alabama at BirminghamGuy McKhann, MD, Principal investigator, Columbia UniversityVincenta Salanova, MD, Principal investigator, Indiana UniversityThomas Pittman, MD, Principal investigator, University of KentuckyAndriana E. Palade, MD, Principal investigator, West Virginia UniversityAviva Abosch, MD, PhD, Principal investigator, University of MinnesotaAnto Bagic, MD, MSc, Principal investigator, University of Pittsburgh, Medical SchoolRobert L Beach, MD, PhD, Principal investigator, Upstate Medical University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00860145
- Sponsor's protocol ID
- U01NS058634
- Other IDs
- CRC, NINDS
- Acronym
- ROSE
- Status last verified
- May 2018
- First submitted
- 11 Mar 2009
- Last updated
- 14 May 2018
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- Yes: Preliminary report 12/2016 at the American Epilepsy Society meeting. Full paper to follow.
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.
PubMed 19243009
Study at a glance
From the registry record, last updated by the sponsor on 14 May 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Radiosurgery Versus Lobectomy for Temporal Lobe Epilepsy
- ClinicalTrials.gov ID
- NCT00860145
- Acronym / sponsor ID
- ROSE / U01NS058634
- Conditions
- Epilepsy
- Keywords
- epilepsy, radiosurgery, temporal lobectomy
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 61 participants (actual)
- Lead sponsor
- University of California, San FranciscoUniversity, hospital or other
- Study start
- Sep 2009
- Primary completion
- 1 Jun 2016 (actual)
- Study completion
- 1 Jul 2016 (actual)
- First posted
- 12 Mar 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| radiosurgery | Experimental | Procedure: radiosurgeryRadiosurgical treatment of the medial temporal lobe |
| temporal lobectomy | Active comparator | Procedure: temporal lobectomyResection of medial temporal lobe |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (20 listed)
- 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.
Key exclusion criteria (0 listed)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| radiosurgeryAlso: Gamma KnifeThe 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. | Procedure or surgery | radiosurgery |
| temporal lobectomyThe 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. | Procedure or surgery | temporal lobectomy |
Primary outcome
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
1 secondary outcome
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 May 2018.
- Background: PubMed 19243009Barbaro 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.
- Individual participant dataSharing planned: Yes. Preliminary report 12/2016 at the American Epilepsy Society meeting. Full paper to follow.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Lawrence Ver Hoef, MD principal investigator
University of Alabama at Birmingham
Guy McKhann, MD principal investigator
Columbia University
Vincenta Salanova, MD principal investigator
Indiana University
14 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing radiosurgery and temporal lobectomy in people with Epilepsy, run by University of California, San Francisco at 14 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 20 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 14 May 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 14 sites in United States, India. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome 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. (time frame: 3 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00860145, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 May 2018.