Clinical trial NCT01734122: Stereotactic Radiosurgery for Essential Tremor and Parkinsonian Tremor
Official title: Stereotactic Radiosurgery for Essential Tremor and Parkinsonian Tremor
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Tremor
Essential Tremor
Parkinson Disease
Radiosurgery
Quality of Life
Keywords: Stereotactic Radiosurgery
Essential Tremor
Parkinsonian Tremor
Quality of Life
Severity of Tremor
Lead sponsor: Vanderbilt University Medical Center
Sponsor class: OTHER
First posted: 2012-11-27
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: This trial enrolls persons with essential tremor or Parkinsonian tremor that is inadequately controlled by medications.

Brief summary: The purpose of this study is to determine the changes in quality of life and degree of tremor for patients with essential tremor or Parkinsonian tremor who are treated by stereotactic radiosurgery (SRS). This is a questionnaire-based study. Please see Detailed Description below for more information.

Detailed description: Tremor is the most common of all movement disorders. Patients with essential tremor (ET) or Parkinsonian tremor (PT) may be severely disabled by their tremor. When the tremor is inadequately controlled by medications, surgical options are often offered. However, some patients may prefer a noninvasive treatment approach and some patients are not surgical candidates for medical reasons.

Stereotactic radiosurgery (SRS) is a treatment that uses high-energy highly-focused radiation (X-rays) to destroy a tiny region in the brain that causes tremor to occur. This region is known as the ventral intermedius nucleus of the thalamus and is the same area targeted by surgical deep brain stimulator (DBS) treatment or neurosurgical operation (thalamotomy). Multiple case series publications using Gamma Knife stereotactic radiation have been reported that show stereotactic radiosurgery is safe and effective treatment for ET and PT, making it a standard treatment for inoperable and inadequately controlled tremor patients. However, radiation treatment by linear accelerator machines are much more common than Gamma Knife treatment machines in the United States, and there are no reports of large series of ET and PT patients treated using linear accelerator-based SRS using a noninvasive mask-based targeting system.

This clinical trial asks the question of whether linear accelerator-based SRS is as safe and effective as that reported for Gamma Knife procedures, and whether it is a valid alternative to surgical thalamotomy or implantation of a deep brain stimulator (DBS) device. The primary measurements are quality of life related to tremor before and after stereotactic radiosurgery treatment, and secondary measurements are degree of tremor severity and usage of tremor-related medications.

Stereotactic Radiosurgery (SRS) is a standard-of-care treatment for patients with severe tremor. This clinical trial is a questionnaire-based trial that only involves completion of 2 questionnaires at the consultation appointments with neurology and radiation oncology. The questionnaires only take a few minutes and will provide us with valuable information about how severe the patient's tremor is before and after SRS treatment at 3-month intervals for 1 year. Currently we are only performing SRS treatment on one side of the brain (effects one side of the body) so the side with the worst tremor is treated.

Financial: All associated steps listed below are considered the Standard of Care to receive SRS treatment for tremor and are billed to the patient's insurance per the usual routine. Patients can receive this treatment without participating in the clinical trial questionnaires. There is no financial support, no compensation, and no travel stipend available to patients who participate in this trial.

What to expect:

1. All patients interested in SRS treatment for tremor must be evaluated by a movement disorder neurologist. The neurologist will assess the severity of the tremor. Your primary physician or outside neurologist must make a referral to the Vanderbilt Movement Disorder Clinic for initial assessment. For clinical trial participation, a questionnaire will be completed as a baseline measurement (this takes a few minutes). If the patient is an appropriate candidate for SRS and there may be additional evaluations and discussion with the entire Movement Disorder group at monthly meetings.

   \*\* Please note: for Parkinson's disease patients, please come to the neurology evaluation "functionally off medication", which means do NOT take the morning dose of Parkinson's related medications.
2. The patient will undergo a neuropsychological evaluation prior to SRS treatment, which is the standard of care for patients considering DBS or SRS treatment.
3. The patient will meet with a neurosurgeon who will be involved in the SRS planning and procedure.
4. Patients referred for SRS treatment will be evaluated by a radiation oncologist, Dr. Austin Kirschner or Dr. Anthony Cmelak. At this appointment, discussion will include descriptions of the procedure in detail and review of the risks and benefits of treatment. For clinical trial participation, a questionnaire will be completed as a baseline assessment of the patient's tremor-related quality of life (this takes a few minutes).
5. If the patient chooses to proceed with SRS, in the department of radiation oncology a tight-fitting thermal plastic mask will be custom made to fit around the patient's head and a CT scan of the head will be performed in radiation oncology. This step takes about 45 minutes.
6. A specialized MRI of the brain will be obtained for treatment planning. This step takes about 1 hour.
7. Approximately 2 weeks after completing all the consultation appointments and obtaining the imaging for treatment planning, the single stereotactic radiation treatment will be performed. The SRS procedure takes approximately 2.5 hours. It is entirely outpatient and does not require anesthesia. The procedure is noninvasive and painless (X-ray treatment). During the entire treatment, the head is held tightly in the plastic mask. Oral anti-anxiety medication may be given to relax the patient.

   Follow-up:
8. At 3 month intervals for 1 year, the patient will have follow-up appointments with radiation oncology and neurology. A brain MRI may be performed at some of these intervals to document the treatment effect on the brain tissue. For participation in the clinical trial, at these follow-up appointments the quality of life questionnaire will be completed at the radiation oncology visit and the severity of tremor questionnaire will be completed at the neurology visit .
9. At 6 months after SRS treatment, a neuropsychological evaluation will be performed.

All patients interested in stereotactic radiosurgery (SRS) or participating in this questionnaire-based clinical trial should feel free to call the contact phone numbers listed below or have their physician refer the patient for consultation with the Movement Disorder Clinic in the neurology department at Vanderbilt.

Eligibility criteria: Inclusion Criteria:

* Must be certified by a neurologist as having essential tremor or Parkinsonian tremor that is insufficiently controlled by medication alone.
* Preference to receive radiation treatment for tremor treatment, rather than surgical DBS implantation or surgical thalamotomy
* At least 18 years old

Exclusion Criteria:

* Contraindications to cranial radiation (such as prior radiation to the thalamus)
* Inability to have a MRI of the brain
* Prior surgical thalamotomy treatment (but contralateral deep brain stimulator \[DBS\] is permitted)
* Estimated life expectancy less than 1 year

Primary outcomes:
measure: Tremor-related Quality of Life
timeFrame: 1 year
Secondary outcomes:
measure: Severity of Tremor
timeFrame: 1 year
measure: Neuropsychological Assessment
timeFrame: Baseline and 6 months post-treatment
Other outcomes:
Locations:
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
Study officials:
References:
citation: Khattab MH, Cmelak AJ, Sherry AD, Luo G, Wang L, Yu H, Hedera P, Phibbs FT, Lindsell CJ, Neimat J, Kirschner AN. Noninvasive Thalamotomy for Refractory Tremor by Frameless Radiosurgery. Int J Radiat Oncol Biol Phys. 2022 Jan 1;112(1):121-130. doi: 10.1016/j.ijrobp.2021.08.021. Epub 2021 Aug 25.