Clinical trial NCT03305588: RAD 1601: EDGE Radiosurgery for Intractable Essential Tremor and Tremor-Dominant Parkinson's Disease
Official title: RAD 1601: Pilot Trial of Frameless Virtual Cone Stereotactic Radiosurgical Thalamotomy for Intractable Tremor and Advanced Functional Connectivity Parcellation of the Thalamus
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Essential Tremor
Parkinson Disease
Keywords: essential tremor (ET)
stereotactic radiosurgery (SRS)
radiosurgery (RS)
deep brain stimulation (DBS)
Parkinson's Disease (PD)
tremor-dominant Parkinson's disease (TDPD)
Lead sponsor: University of Alabama at Birmingham
Sponsor class: OTHER
First posted: 2017-10-10
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: To determine the efficacy of frameless Virtual Cone Radiosurgical Thalamotomy for medically refractory tremor resulting from either Essential Tremor or Tremor-Dominant Parkinson's Disease with the Fahn-Tolosa-Marin Tremor Rating Scale (FTMTRS) in patients who are not candidates for deep brain stimulation (DBS).

Detailed description: Per the National Institute of Neurological Disorders and Stroke, tremor is an involuntary, rhythmic muscle contraction leading to shaking movements in one or more parts of the body. It is a common movement disorder that most often affects the upper extremities but can also occur in the head, vocal cords, torso, and lower extremities. Tremor may be intermittent or constant. It can be present at rest, during action, or mixed between rest and action.

Tremor can occur at any age but it is most common among middle-aged and older adults; once it occurs, it often progresses over time. This disorder shows no gender predilection. Although tremor is not life threatening, it can be severely disabling, making it difficult or even impossible to perform work and daily life tasks.

Deep parts of the brain that control movements appear to be involved in tremor development. However, most types of tremor have no actual known cause. There are some forms that appear to be inherited and run in families. There are more than 20 types of tremor. Tremor can occur on its own (such as essential tremor (ET) or be associated with other neurological disorders, such as Parkinson's disease (PD).

Tremor is a common symptom of Parkinson's disease. The classification of patients with Parkinson's disease into tremor-dominant and non-tremor subtypes is well established. The pathophysiology of tremor in patients with tremor-dominant Parkinson's disease (TDPD) may be distinct from other their other symptoms, such as bradykinesia, rigidity, and gait and balance symptoms. Importantly, tremor in PD responds less well or can even be highly resistant to dopaminergic treatment than bradykinesia and rigidity. Therefore other treatment strategies may need to be considered.

Essential Tremor (ET) is a common neurologic condition characterized by a tremor that can occur either with posture or action. In the US, there are reported to be as many as 10 million people with essential tremor. A significant subset of patients experience persistent disability and disruption on activities of daily living from tremor and require intervention.

Treatment approach depends on the penetrance of disability into a patient's life, but typically begins with pharmacologic intervention. Patients with disabling tremor refractory to primary and secondary pharmacologic interventions are evaluated for surgical treatment with deep brain stimulation (DBS) or thalamotomy. However, a sizeable subset of these patients are unfavorable candidates for surgery due to medical or neurological co-morbidities. Additionally, a significant subset of patients simply does not wish to undergo the awake craniotomy required for DBS lead placement for tremor. Stereotactic radiosurgery (SRS) thalamotomy is an alternative for those patients. SRS thalamotomy targets the ventral intermediate (VIM) nucleus of the thalamus based on predetermined stereotactic coordinates.

Almost all prior SRS thalamotomy studies performed have used the Leksell Gamma Knife treatment unit and demonstrate that about 80% of properly selected patients respond. The efficacy of Gamma Knife radiosurgery for tremor has been studied prospectively and has been modeled based upon prognostic factors in larger retrospective studies. These studies provide benchmarks for measuring the safety and efficacy of frameless Virtual Cone radiosurgery in this trial. In order for possible frameless Virtual Cone radiosurgery to be a standard of care in the treatment of tremor, additional clinical data is required. This pilot trial of Virtual Cone radiosurgery will assess the safety and efficacy of this treatment. A target of forty patients will be treated to confirm the feasibility of the protocol procedures, efficacy, and safety of the treatment. Secondary endpoints will include quality of life and patient satisfaction. The investigators hypothesize that the recent improvements in LINAC delivery, image guidance, and patient position monitoring will allow a safe frameless procedure that has a high patient satisfaction and low toxicity.

Eligibility criteria: Inclusion Criteria:

* Patients with medical refractory essential tremor or tremor-dominant Parkinson's disease that are not candidates for deep brain stimulation (DBS), either by medical/surgical co-morbidities or by choice.
* Patients must have an ECOG status of 0, 1, or 2.
* Patients must be at least 18 years of age.
* All patients must be given written informed consent.

Exclusion Criteria:

* Patients who have had prior radiosurgery or therapeutic brain radiation therapy.
* Patients with medical contra-indications to MRI imaging (e.g. pacemaker).

Primary outcomes:
measure: Overall tremor reduction proportion evaluated by the Fahn-Tolosa-Marin Tremor Rating Scale (FTMTRS)
timeFrame: From Baseline up to 36 months following completion of radiosurgery
Secondary outcomes:
measure: Number of Participants with treatment-related adverse events
timeFrame: From Baseline up to 36 months following completion of radiosurgery
measure: Changes in resting-state functional MRI (fMRI) and diffusion tensor patterns associated with Radiosurgical thalamotomy
timeFrame: From Baseline up to 36 months following completion of radiosurgery
measure: Mean of Quality of Life Scores measured by SF-36 questionnaire
timeFrame: From Baseline up to 36 months following completion of radiosurgery
measure: Mean of Quality of Life Scores measured by PROMIS Upper Extremity Questionnaire
timeFrame: From Baseline up to 36 months following completion of radiosurgery
measure: Patient Satisfaction Scores
timeFrame: 3 Month Follow-Up Visit
measure: Define Targeting Methods within Thalamus based on Structural and Functional Connectivity
timeFrame: From Baseline up to 36 months following completion of radiosurgery
measure: Mean of Quality of Life Scores measured by the Essential Tremor Rating Assessment Scale (TETRAS)
timeFrame: From Baseline up to 36 months following completion of radiosurgery
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham (UAB) Hazelrig-Salter Radiation Oncology Center
state: Alabama
Study officials:
affiliation: University of Alabama at Birmingham
name: John Fiveash, MD
role: PRINCIPAL_INVESTIGATOR
References: