Stereotactic Radiosurgery in the Treatment of Essential Tremor (EASIER)

Stereotactic Radiosurgery in the Treatment of Tremor in Patients with Essential Tremor - a Randomized Phase II Study

The goal of this interventional study is to evaluate the effectiveness of treatment using stereotactic radiosurgery in the treatment of essential tremor in adult patients

Study Overview

• Status: Recruiting
• Conditions: Essential Tremor
• Intervention / Treatment: Radiation: Stereotactic Radiosurgery; Radiation: Stereotactic Radiosurgery

Detailed Description

The study will include patients diagnosed with essential tremor who have insufficient tremor control despite the use of available pharmacotherapy methods. The study will include patients who have been disqualified from the Deeply Brain Stimulation procedure or who do not consent to its performance. Additional conditions for the examination are age over 50 and the duration of the disease over 5 years.

After qualifying and giving written informed consent, the patient will be randomly assigned to one of two study arms:

1. control arm: patients irradiated with the CyberKnife with a dose of 130 Gy
2. test arm: patients irradiated with the CyberKnife with a dose of 80 Gy

The primary aim of the study is to determine the effectiveness of radiosurgery in patients with essential tremor. Secondary objectives will be to determine the impact of treatment on the quality of life of, as well as to assess the safety and possible complications of radiosurgery.

• Study Type: Interventional
• Enrollment (Estimated): 42
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Aleksandra Napieralska; Phone Number: 48322788056; Email: aleksandra.napieralska@gliwice.nio.gov.pl
• Study Contact Backup: Name: Agnieszka Szczyrba; Phone Number: 48322788001; Email: agnieszka.szczyrba@gliwice.nio.gov.pl

Study Locations

• Poland
  • Gliwice, Poland, 44-101
    • Recruiting
    • Maria Skłodowska-Curie National Research Institute of Oncology, Gliwice Branch
    • Contact: Aleksandra Napieralska; Phone Number: 48322788056; Email: aleksandra.napieralska@gliwice.nio.gov.pl

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Essential tremor diagnosed, Parkinson's disease and other causes of tremor excluded.
• Insufficient tremor control despite the use of available pharmacotherapy methods.
• Disqualification from the Deeply Brain Stimualtion procedure/lack of consent to perform it on the side qualified for Stereotactic Radiosurgery
• Consent to participate in a clinical trial.

Exclusion Criteria:

• Age under 50
• Pregnancy
• Duration of the disease less than 5 years
• Dementia, psychosis or other condition that prevents giving informed consent to participate in the study
• Poor general condition, serious comorbidities
• Structural changes in the basal ganglia or major atrophic changes
• Previous radiotherapy to the brain covering the potential treatment area
• Medical contraindications to magnetic resonance imaging

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: A; Patients irradiated with the CyberKnife with a dose of 130 Gy	Radiation: Stereotactic Radiosurgery; Frameless Stereotactic Radiosurgery- CyberKnife with a dose of 80 Gy; Radiation: Stereotactic Radiosurgery; Frameless Stereotactic Radiosurgery- CyberKnife with a dose of 130 Gy
Experimental: B; Patients irradiated with the CyberKnife with a dose of 80 Gy	Radiation: Stereotactic Radiosurgery; Frameless Stereotactic Radiosurgery- CyberKnife with a dose of 80 Gy; Radiation: Stereotactic Radiosurgery; Frameless Stereotactic Radiosurgery- CyberKnife with a dose of 130 Gy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Treatment Efficacy	Efficacy of radiosurgery treatment in patients with essential tremor assessed on a dedicated tremor severity scale - Fahn-Tolosa-Marin (FTM)	24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quality of life	The impact of treatment on the quality of life of patients based on the dedicated Quality of Life in Essential Tremor questionnaire	24 months
Safety	Safety and possible complications of radiosurgery assesed in Common Terminology Criteria for Adverse Events (CTCAE) v5.0	24 months

Collaborators and Investigators

• Sponsor: Maria Sklodowska-Curie National Research Institute of Oncology
• Investigators: Principal Investigator: Aleksandra Napieralska, Maria Skłodowska-Curie National Research Institute of Oncology, Gliwice Branch

Publications and helpful links

General Publications

• Hooper AK, Okun MS, Foote KD, Fernandez HH, Jacobson C, Zeilman P, Romrell J, Rodriguez RL. Clinical cases where lesion therapy was chosen over deep brain stimulation. Stereotact Funct Neurosurg. 2008;86(3):147-52. doi: 10.1159/000120426. Epub 2008 Mar 12.
• Niranjan A, Jawahar A, Kondziolka D, Lunsford LD. A comparison of surgical approaches for the management of tremor: radiofrequency thalamotomy, gamma knife thalamotomy and thalamic stimulation. Stereotact Funct Neurosurg. 1999;72(2-4):178-84. doi: 10.1159/000029723.
• Young RF, Shumway-Cook A, Vermeulen SS, Grimm P, Blasko J, Posewitz A, Burkhart WA, Goiney RC. Gamma knife radiosurgery as a lesioning technique in movement disorder surgery. J Neurosurg. 1998 Aug;89(2):183-93. doi: 10.3171/jns.1998.89.2.0183.
• Stancanello J, Romanelli P, Pantelis E, Sebastiano F, Modugno N. Atlas-based functional radiosurgery: early results. Med Phys. 2009 Feb;36(2):457-63. doi: 10.1118/1.3056460.
• LEKSELL L. The stereotaxic method and radiosurgery of the brain. Acta Chir Scand. 1951 Dec 13;102(4):316-9. No abstract available.
• Lindquist C, Kihlstrom L, Hellstrand E. Functional neurosurgery--a future for the gamma knife? Stereotact Funct Neurosurg. 1991;57(1-2):72-81. doi: 10.1159/000099557.
• Duma CM. Movement disorder radiosurgery--planning, physics and complication avoidance. Prog Neurol Surg. 2007;20:249-266. doi: 10.1159/000100168.
• Franzini A, Marchetti M, Brait L, Milanesi I, Messina G, Forapani E, Broggi G, Fariselli L. Deep brain stimulation and frameless stereotactic radiosurgery in the treatment of bilateral parkinsonian tremor: target selection and case report of two patients. Acta Neurochir (Wien). 2011 May;153(5):1069-75. doi: 10.1007/s00701-011-0962-0. Epub 2011 Feb 20.
• Yu C, Main W, Taylor D, Kuduvalli G, Apuzzo ML, Adler JR Jr. An anthropomorphic phantom study of the accuracy of Cyberknife spinal radiosurgery. Neurosurgery. 2004 Nov;55(5):1138-49. doi: 10.1227/01.neu.0000141080.54647.11.
• Hopfner F, Haubenberger D, Galpern WR, Gwinn K, Van't Veer A, White S, Bhatia K, Adler CH, Eidelberg D, Ondo W, Stebbins GT, Tanner CM, Helmich RC, Lenz FA, Sillitoe RV, Vaillancourt D, Vitek JL, Louis ED, Shill HA, Frosch MP, Foroud T, Kuhlenbaumer G, Singleton A, Testa CM, Hallett M, Elble R, Deuschl G. Knowledge gaps and research recommendations for essential tremor. Parkinsonism Relat Disord. 2016 Dec;33:27-35. doi: 10.1016/j.parkreldis.2016.10.002. Epub 2016 Oct 4.
• Louis ED, Ferreira JJ. How common is the most common adult movement disorder? Update on the worldwide prevalence of essential tremor. Mov Disord. 2010 Apr 15;25(5):534-41. doi: 10.1002/mds.22838.
• Bhatia KP, Bain P, Bajaj N, Elble RJ, Hallett M, Louis ED, Raethjen J, Stamelou M, Testa CM, Deuschl G; Tremor Task Force of the International Parkinson and Movement Disorder Society. Consensus Statement on the classification of tremors. from the task force on tremor of the International Parkinson and Movement Disorder Society. Mov Disord. 2018 Jan;33(1):75-87. doi: 10.1002/mds.27121. Epub 2017 Nov 30.
• Jackson AL, Murphy LL. Role of the hypothalamic-pituitary-adrenal axis in the suppression of luteinizing hormone release by delta-9-tetrahydrocannabinol. Neuroendocrinology. 1997 Jun;65(6):446-52. doi: 10.1159/000127208.
• Bretsztajn L, Gedroyc W. Brain-focussed ultrasound: what's the "FUS" all about? A review of current and emerging neurological applications. Br J Radiol. 2018 Jul;91(1087):20170481. doi: 10.1259/bjr.20170481. Epub 2018 Mar 6.
• Martinez-Moreno NE, Sahgal A, De Salles A, Hayashi M, Levivier M, Ma L, Paddick I, Regis J, Ryu S, Slotman BJ, Martinez-Alvarez R. Stereotactic radiosurgery for tremor: systematic review. J Neurosurg. 2018 Feb 23;130(2):589-600. doi: 10.3171/2017.8.JNS17749. Print 2019 Feb 1.
• 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.
• Kim W, Sharim J, Tenn S, Kaprealian T, Bordelon Y, Agazaryan N, Pouratian N. Diffusion tractography imaging-guided frameless linear accelerator stereotactic radiosurgical thalamotomy for tremor: case report. J Neurosurg. 2018 Jan;128(1):215-221. doi: 10.3171/2016.10.JNS161603. Epub 2017 Feb 24.
• Goc B, Roch-Zniszczol A, Larysz D, Zarudzki L, Stapor-Fudzinska M, Rozek A, Wozniak G, Boczarska-Jedynak M, Miszczyk L, Napieralska A. The Effectiveness and Toxicity of Frameless CyberKnife Based Radiosurgery for Parkinson's Disease-Phase II Study. Biomedicines. 2023 Jan 20;11(2):288. doi: 10.3390/biomedicines11020288.
• Solberg TD, Medin PM, Mullins J, Li S. Quality assurance of immobilization and target localization systems for frameless stereotactic cranial and extracranial hypofractionated radiotherapy. Int J Radiat Oncol Biol Phys. 2008;71(1 Suppl):S131-5. doi: 10.1016/j.ijrobp.2007.05.097.
• Luo G, Neimat JS, Cmelak A, Kirschner AN, Attia A, Morales-Paliza M, Ding GX. Margin of error for a frameless image guided radiosurgery system: Direct confirmation based on posttreatment MRI scans. Pract Radiat Oncol. 2017 May-Jun;7(3):e223-e231. doi: 10.1016/j.prro.2016.08.006. Epub 2016 Aug 20.
• Campbell AM, Glover J, Chiang VL, Gerrard J, Yu JB. Gamma knife stereotactic radiosurgical thalamotomy for intractable tremor: a systematic review of the literature. Radiother Oncol. 2015 Mar;114(3):296-301. doi: 10.1016/j.radonc.2015.01.013. Epub 2015 Feb 14.
• Hashim M, Vincken T, Kroi F, Gebregergish S, Spencer M, Wang J, Kampfenkel T, Lam A, He J. A systematic review of noninferiority margins in oncology clinical trials. J Comp Eff Res. 2021 Apr;10(6):443-455. doi: 10.2217/cer-2020-0200. Epub 2021 Mar 17.
• Palesch YY. Some common misperceptions about P values. Stroke. 2014 Dec;45(12):e244-6. doi: 10.1161/STROKEAHA.114.006138. Epub 2014 Nov 6. No abstract available.
• Chow S-C., Shao J., Wang H., Lokhnygina Y. Sample Size Calculations in Clinical Research. Third ed: Chapman and Hall/CRC; 2017.

Study record dates

Study Major Dates

• Study Start (Actual): December 16, 2024
• Primary Completion (Estimated): May 1, 2030
• Study Completion (Estimated): May 1, 2030

Study Registration Dates

• First Submitted: February 6, 2025
• First Submitted That Met QC Criteria: February 6, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 6, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Keywords: stereotactic radiosurgery; CyberKnife; tremor; frameless radiosurgery; essenstial tremor
• Additional Relevant MeSH Terms: Neurologic Manifestations; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Dyskinesias; Tremor; Essential Tremor
• Other Study ID Numbers: EASIER

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No