| CTRI Number |
CTRI/2011/07/001918 [Registered on: 26/07/2011] Trial Registered Prospectively |
| Last Modified On: |
20/11/2019 |
| Post Graduate Thesis |
No |
| Type of Trial |
Interventional |
|
Type of Study
|
Medical Device
Surgical/Anesthesia |
| Study Design |
Randomized, Parallel Group Trial |
|
Public Title of Study
|
Gamma Knife radiosurgery or Open Surgery for Epilepsy |
|
Scientific Title of Study
|
Radio surgery or Open surgery for Epilepsy (ROSE) Trial |
| Trial Acronym |
ROSE |
|
Secondary IDs if Any
|
| Secondary ID |
Identifier |
| NCT00860145 |
ClinicalTrials.gov |
|
|
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
|
| Name |
Prof AK Mahapatra |
| Designation |
HOD Neurosurgery |
| Affiliation |
|
| Address |
All India Institute of Medical Sciences (AIIMS)
Ansari Nagar, New Delhi
New Delhi
DELHI
1100029
India |
| Phone |
|
| Fax |
|
| Email |
akmahapatra_22000@yahoo.com |
|
Details of Contact Person
Scientific Query
|
| Name |
Prof AK Mahapatra |
| Designation |
HOD Neurosurgery |
| Affiliation |
|
| Address |
All India Institute of Medical Sciences (AIIMS)
Ansari Nagar, New Delhi
New Delhi
DELHI
1100029
India |
| Phone |
|
| Fax |
|
| Email |
akmahapatra_22000@yahoo.com |
|
Details of Contact Person
Public Query
|
| Name |
Prof AK Mahapatra |
| Designation |
HOD Neurosurgery |
| Affiliation |
|
| Address |
All India Institute of Medical Sciences (AIIMS)
Ansari Nagar, New Delhi
New Delhi
DELHI
1100029
India |
| Phone |
|
| Fax |
|
| Email |
akmahapatra_22000@yahoo.com |
|
|
Source of Monetary or Material Support
|
| University of California San Francisco |
|
|
Primary Sponsor
|
| Name |
National Institute of Health |
| Address |
National Institute of Neurological Disorders and Stroke (NINDS)
Office of the Director
Building 31, Room 8A52 31 Center Drive MSC 2540, Bethesda, Maryland, UNITED STATES 20892-2540 |
| Type of Sponsor |
Government funding agency |
|
|
Details of Secondary Sponsor
|
| Name |
Address |
| University of California San Francisco |
Department of
Neurological Surgery
University of California San Francisco, California, US- 94143 |
|
|
Countries of Recruitment
|
India
United Kingdom
United States of America |
|
Sites of Study
|
| No of Sites = 2 |
| Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
| Prof AK Mahapatra |
All India Institute of Medical Sciences |
720, 7th Floor, Neurosurgery Dept,AIIMS
ANSARI NAGAR NEW DELHI
New Delhi
DELHI |
011-26588927
akmahapatra_22000@yahoo.com |
| Dr Jayant Misra |
Vidyasagar Institute of Mental Health and Neuro sciences |
RANCAN Gamma Knife Center, VIMHANS
Industrial Area, Nehru Nagar
New Delhi
DELHI |
9810139245
misra.jayant@gmail.com |
|
Details of Ethics Committee
Modification(s)
|
| No of Ethics Committees= 1 |
| Name of Committee |
Approval Status |
| All India Institute of Medical Sciences |
Approved |
|
|
Regulatory Clearance Status from DCGI
|
|
|
Health Condition / Problems Studied
|
| Health Type |
Condition |
| Patients |
Epilepsy
, |
|
|
Intervention / Comparator Agent
|
| Type |
Name |
Details |
| Intervention |
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 patients head.
|
| Comparator Agent |
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.
|
|
|
Inclusion Criteria
|
| Age From |
18.00 Year(s) |
| Age To |
99.00 Year(s) |
| Gender |
Both |
| Details |
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.
|
|
| ExclusionCriteria |
| Details |
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 are excluded.
18.Patients who can not be anticipated to participate for the full 36 months of the trial will be excluded.
|
|
|
Method of Generating Random Sequence
|
Stratified randomization |
|
Method of Concealment
|
On-site computer system |
|
Blinding/Masking
|
Participant, Investigator and Outcome Assessor Blinded |
|
Primary Outcome
|
| Outcome |
TimePoints |
| •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. |
•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. |
|
|
Secondary Outcome
|
| Outcome |
TimePoints |
| •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 |
|
|
Target Sample Size
|
Total Sample Size="234"
Sample Size from India="50"
Final Enrollment numbers achieved (Total)= "0"
Final Enrollment numbers achieved (India)="0" |
|
Phase of Trial
|
Phase 3 |
|
Date of First Enrollment (India)
|
29/08/2011 |
| Date of Study Completion (India) |
Date Missing |
| Date of First Enrollment (Global) |
03/05/2010 |
| Date of Study Completion (Global) |
Date Missing |
|
Estimated Duration of Trial
|
Years="5"
Months="2"
Days="0" |
Recruitment Status of Trial (Global)
Modification(s)
|
Completed |
| Recruitment Status of Trial (India) |
Completed |
|
Publication Details
|
None yet |
|
Individual Participant Data (IPD) Sharing Statement
|
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
|
|
Brief Summary
|
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. |