RAD 1601: EDGE Radiosurgery for Intractable Essential Tremor and Tremor-Dominant Parkinson's Disease

NCT ID: NCT03305588

Last Updated: 2025-10-15

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: NA
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-12-05
• Study Completion Date: 2026-02-01

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.

Conditions

Essential Tremor; Parkinson Disease

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

130 Gy Radiation & Unframed Virtual Cone

130 Gy Virtual Cone Radiosurgery Unframed (Face Mask)

Group Type: EXPERIMENTAL

Unframed Virtual Cone

Intervention Type: DEVICE

The patient will undergo stereotactic radiosurgery. Radiosurgery is a single non-surgical radiation treatment and will be done as an outpatient procedure. High-energy radiation will be delivered to a small, precise area of the patient's brain using a linear accelerator. A face mask (unframed) will be placed over the patient's face to keep their head from moving during the procedure. During the procedure, the study doctor will confirm the exact location that needs to be treated using x-rays and optical imaging cameras. The face mask will hold the patient's head to prevent it from moving and to focus the x-rays and aim them on a small area in the thalamus of the patient's brain. For most patients, the actual time on the radiosurgery treatment machine is 30 to 60 minutes. The face mask will be removed after the treatment.

Interventions

Unframed Virtual Cone

The patient will undergo stereotactic radiosurgery. Radiosurgery is a single non-surgical radiation treatment and will be done as an outpatient procedure. High-energy radiation will be delivered to a small, precise area of the patient's brain using a linear accelerator. A face mask (unframed) will be placed over the patient's face to keep their head from moving during the procedure. During the procedure, the study doctor will confirm the exact location that needs to be treated using x-rays and optical imaging cameras. The face mask will hold the patient's head to prevent it from moving and to focus the x-rays and aim them on a small area in the thalamus of the patient's brain. For most patients, the actual time on the radiosurgery treatment machine is 30 to 60 minutes. The face mask will be removed after the treatment.

Intervention Type: DEVICE

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).

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 99 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Alabama at Birmingham

OTHER

Sponsor Role: lead

Responsible Party

John Fiveash, MD

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

John Fiveash, MD

Role: PRINCIPAL_INVESTIGATOR

University of Alabama at Birmingham

Locations

University of Alabama at Birmingham (UAB) Hazelrig-Salter Radiation Oncology Center

Birmingham, Alabama, United States

Countries

United States

References

Middlebrooks EH, Popple RA, Greco E, Okromelidze L, Walker HC, Lakhani DA, Anderson AR, Thomas EM, Deshpande HD, McCullough BA, Stover NP, Sung VW, Nicholas AP, Standaert DG, Yacoubian T, Dean MN, Roper JA, Grewal SS, Holland MT, Bentley JN, Guthrie BL, Bredel M. Connectomic Basis for Tremor Control in Stereotactic Radiosurgical Thalamotomy. AJNR Am J Neuroradiol. 2023 Feb;44(2):157-164. doi: 10.3174/ajnr.A7778. Epub 2023 Jan 26.

Reference Type: DERIVED

PMID: 36702499 (View on PubMed)

Other Identifiers

IRB-160811009

Identifier Type: -

Identifier Source: org_study_id