We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Precision Radiation Treatment for Epilepsy (PRECISION) (PRECISION)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05182437
Recruitment Status : Not yet recruiting
First Posted : January 10, 2022
Last Update Posted : January 10, 2022
Sponsor:
Collaborators:
Maastricht University Medical Center
UMC Utrecht
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
ZonMw: The Netherlands Organisation for Health Research and Development
Information provided by (Responsible Party):
Maastricht Radiation Oncology

Brief Summary:
The PRECISION-study offers a non-invasive, curative intervention for drug-resistant localised epilepsy patients who are not eligible for surgery. The intervention will consist of a single LINAC based SRT treatment and is given by the radiation-oncologist after detailed localisation of the epileptogenic zone with the neurologist, radiologist and neurosurgeon. This intervention will make curative-intent treatment possible where this could otherwise not be given and is a non-invasive and non-competitive alternative to epilepsy surgery. It is expected that the health costs for this curative treatment will not exceed standard treatment, such as lifelong medication and neuromodulation.

Condition or disease Intervention/treatment Phase
Epilepsy Radiation: LINAC-based Stereotactic Radiotherapy Not Applicable

Detailed Description:

In this PRECISION-study including adult patients with drug-resistant, localised epilepsy, not eligible for surgery, we offer non-invasive linear accelerator (LINAC) based Stereotactic Radiotherapy (SRT) with curative intent.

SRT and stereotactic radio-surgery (SRS) have been used to treat several types of neoplasms in the brain for several decades. Several publications (level 2 evidence) have shown the potential value of SRT in patients with drug-resistant epilepsy, however no level-1 evidence was given enabling guideline development. A recent systematic review from our institution has shown that SRT resulted in a significant seizure cure or reduction in 58% of the 170 included patients, within 2 years after treatment. Interestingly, the ROSE trial, randomising between open surgery and SRT, has demonstrated a seizure remission of 52% in the radiotherapy group after 2 years with the proportion of seizure-free patients still increasing with a longer follow-up up to 74% after 3 years. Therefore, SRT may be considered a curative treatment for drug resistant localised epilepsy. Currently, randomized controlled SRT epilepsy trials are lacking and there is a need for high quality evidence, so SRT can be clinically implemented for localised drug-resistant epilepsy patients in the Netherlands as well.

In the PRECISION-study, patients will be randomised in a 1:1 ratio between SRT and current standard care, where the latter includes AEDs and neuromodulation (i.e. DBS or VNS and/or AED continuation). We hypothesize that SRT alters the epileptogenic cerebral tissue to yield a reduction in seizures and possibly cure after 2 years, with a significant increase in the patients' quality of life.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 94 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Randomized controlled trial Observational Model : Experimental Time Perspective : Prospective
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Precision Radiation Treatment for Epilepsy (PRECISION)
Estimated Study Start Date : January 1, 2023
Estimated Primary Completion Date : January 1, 2028
Estimated Study Completion Date : January 1, 2028

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Epilepsy

Arm Intervention/treatment
Experimental: LINAC-based Stereotactic Radiotherapy
The intervention will consist of a single LINAC based SRT treatment and is given by the radiation-oncologist after detailed localisation of the epileptogenic zone (EZ) with the neurologist, radiologist and neurosurgeon.
Radiation: LINAC-based Stereotactic Radiotherapy
Target definition: the target volume is defined as the epileptogenic zone (EZ) on all (non) invasive examinations (e.g. 3, 7 Tesla MRI or Stereo-EEG) of the presurgical path. Planning target volume (PTV) = GTV. A single fraction SRT with a prescribed isotoxic dose of 24 Gy to the 100% surrounding isodose. Dose is depending on the proximity and maximum tolerable dose to the radiosensitive organs at risk and EZ volume resulting in a V12<= 10 cc reducing the risk on radionecrosis.

No Intervention: Current standard care
Current standard care includes anti-epileptic drugs and neuromodulation (i.e. Deep Brain Stimulation or Vagus Nerve Stimulation and/or Anti-epileptic continuation).



Primary Outcome Measures :
  1. Radiotherapy adapted Engel classification (RAEC) is I, II or III [ Time Frame: Baseline (before treatment), 1 year, 2 year, 3 year, 4 year and 5 year after treatment ]
    Radiotherapy adapted Engel classification (RAEC). For analysis of outcomes in the incidence of seizures, we use in this study the Engel classification, adapted for radiotherapy. This includes four classes: class I - seizure free, class II - rarely seizures, class III improved, more than 75% IV- no significant improvement.


Secondary Outcome Measures :
  1. Seizure frequency [ Time Frame: Baseline (before treatment), 1 year, 2 year, 3 year, 4 year and 5 year after treatment ]
    self-reports and reports from caretakers, combined in a digital diary.

  2. Seizure-free days [ Time Frame: Baseline (before treatment), 1 year, 2 year, 3 year, 4 year and 5 year after treatment ]
    self-reports and reports from caretakers, combined in a digital diary.

  3. Type of epilepsy [ Time Frame: Baseline (before treatment), 1 year, 2 year, 3 year, 4 year and 5 year after treatment ]
    self-reports and reports from caretakers, combined in a digital diary.

  4. EQ-5D 5 Level (EQ-5D-5L) [ Time Frame: Baseline (before treatment), 1 year, 2 year, 3 year, 4 year and 5 year after treatment ]
    EQ-5D-5L is comprised of a descriptive system and a visual analogue scale. The descriptive system measures quality of life along five dimensions, including mobility, self-care, usual activities, pain/discomfort, and anxiety/depression, with five levels for each dimension from which subjects are asked to select one. There are 5 questions and 5 qualitative answers plus a numerical scale (from 0 to 100) related with the general health status. We will attribute a numerical value to the 5 qualitative answers (100 for the best/ 75, 50, 25 and 0 for the worse).

  5. The Assessment of Quality of Life-8 Dimensions Score (AQoL-8D Score) [ Time Frame: Baseline (before treatment), 1 year, 2 year, 3 year, 4 year and 5 year after treatment ]
    The Assessment of Quality of Life (AQoL) measure of health-related Quality of Life. AQoL-8D covers dimensions of Independent Living, Happiness, Mental Health Coping, Relationships, Self-Worth, Pain, and Senses. Items are scored from 0 to 3. Scores range from 0 to 45 with higher scores indicating poorer quality of life

  6. Quality of life in Epilepsy-31 Inventory (QOLIE-31) [ Time Frame: Baseline (before treatment), 1 year, 2 year, 3 year, 4 year and 5 year after treatment ]

    The QOLIE includes 31 questions about health and daily activities. Responses are given on a range of scales. Responses are coded to 0 to 100 point scales where higher scores indicate better quality of life. The final score is the average of scores for the individual items.

    QOLIE-31 is a widely used epilepsy-specific questionnaire


  7. 'Cost-effectiveness Resource use' is measured with iMTA Productivity Cost Questionnaire (iPCQ) [ Time Frame: Baseline (before treatment), 1 year, 2 year, 3 year, 4 year and 5 year after treatment ]
    Institute for Medical Technology Assessment (iMTA) Productivity Cost Questionnaire (iPCQ). The iPCQ is a standardized instrument for measuring and valuing health related productivity losses. This wil be used for the cost effectiveness analysis.

  8. 'Cost-effectiveness Resource use' is measured with iMTA Medical Consumption Questionnaire (iMCQ) [ Time Frame: Baseline (before treatment), 1 year, 2 year, 3 year, 4 year and 5 year after treatment ]

    Institute for Medical Technology Assessment (iMTA) Medical Consumption Questionnaire (iMCQ). The iMCQ is a standardized instrument for measuring medical costs.

    The aim of the iVICQ is to facilitate and promote an accurate description of providing informal care, its effects on informal caregivers, and how such effects are included in economic evaluations of health care interventions.


  9. 'Informal care' is meausured with iMTA Valuation of Informal Care Questionnaire (iVICQ) [ Time Frame: Baseline (before treatment), 1 year, 2 year, 3 year, 4 year and 5 year after treatment ]

    Institute for Medical Technology Assessment (iMTA) Valuation of Informal Care Questionnaire (iVICQ).

    The aim of this standardized instrument is to facilitate and promote an accurate description of providing informal care, its effects on informal caregivers, and how such effects are included in economic evaluations of health care interventions.


  10. 'Patients' experiences' are measured with the instrument 'Patient Reported Experience Measures Medical Specialtic Care' (PREM MSZ) Medical Specialistic Care (PREM MSZ) [ Time Frame: Baseline (before treatment), 1 year, 2 year, 3 year, 4 year and 5 year after treatment ]
    PREM MSZ is a Dutch standardized questionnaire to report Patient Reported Experience. Instrument is developed by NIVEL (Dutch Institute for Healthcare Research) in collabaration with Dutch healcare insurers. Instrument includes 13 questions about the satisfaction with the communication between the patient and the caregiver, shared decision making, trust in the expertise of the physician, the effect of the treatment. Responses to these questions are coded into 0 to 10 points. Higher scores indicate higher satisfaction with care. In the questionnaire patients are also asked for the evaluation of their own health, recommendations to improve care, and if they would recommend the care to other patients with the same health problem. Finally there are some questions about background variables (age, gender, education)



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age ≥ 18 years, non-pregnant, written informed consent
  • The patient or caretaker is able to keep an epilepsy diary
  • The patient has a diagnosis of epilepsy established by a dedicated Neurologist
  • The patient had at least 3 focal-onset seizures with impairment of consciousness over a 3-month period despite two or more antiepileptic medication trials
  • There is sufficient continuous video electroencephalography to determine a unilateral medial temporal seizure focus
  • There is imaging evidence (i.e. MRI) of the anatomic region to be targeted correlating with the diagnosis of epilepsy
  • The proposed anatomic region to be targeted aligns with anatomy associated with seizure reduction following focal treatment in literature
  • A Wada test or a functional MRI to lateralize language has been performed
  • The patient has completed a standard battery of neuropsychological testing
  • There is absence of neurological or visual deficits outside of seizure episodes
  • The patient been deemed an appropriate candidate for stereotactic radiosurgery by a dedicated Radiation Oncologist and Neurosurgeon
  • Ability to give written informed consent

Exclusion Criteria:

  • Supratentorial abnormalities on brain MRI
  • Neurological or visual deficits outside of seizure episodes
  • History of psychiatric diagnoses
  • Pregnancy

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05182437


Contacts
Layout table for location contacts
Contact: Daniëlle Eekers, Dr. +3188 44 55 600 danielle.eekers@maastro.nl
Contact: Inge Compter, Drs. +3188 44 55 600 inge.compter@maastro.nl

Locations
Layout table for location information
Netherlands
Maastricht Radiation Oncology
Maastricht, Limburg, Netherlands, 6202 AZ
Contact: Danielle Eekers, Dr.    +31884455600    danielle.eekers@maastro.nl   
Contact: Inge Compter, Drs.    +31884455600    inge.compter@maastro.nl   
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UVA)
Amsterdam, Noord-Holland, Netherlands, 1007 MB
Contact: Edith Dieleman, drs.    +31-20-5663433    e.m.dieleman@amsterdamumc.nl   
UMC Utrecht
Utrecht, Netherlands
Contact: Joost Verhoeff, Dr.    +31-88-7558800    J.J.C.Verhoeff-10@umcutrecht.nl   
Sponsors and Collaborators
Maastricht Radiation Oncology
Maastricht University Medical Center
UMC Utrecht
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
ZonMw: The Netherlands Organisation for Health Research and Development
Investigators
Layout table for investigator information
Principal Investigator: Daniëlle Eekers, Dr. Radiation Oncologist
Additional Information:
Publications of Results:
Layout table for additonal information
Responsible Party: Maastricht Radiation Oncology
ClinicalTrials.gov Identifier: NCT05182437    
Other Study ID Numbers: 80-86200-98- 25008
First Posted: January 10, 2022    Key Record Dates
Last Update Posted: January 10, 2022
Last Verified: January 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Epilepsy
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases