Cyclic Deep Brain Stimulation in Essential Tremor

• Sponsor: King's College Hospital NHS Trust (Other)
• Overall Status: Recruiting
• CT.gov ID: NCT04260971
• Collaborator: (none)
• Enrollment: 15
• Location: 1
• Arms: 2
• Anticipated Duration (Months): 34.2
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

The aim of the study is to prove the efficacy and safety of cyclical deep brain stimulation (DBS) in patients with essential tremor, and demonstrate non-inferiority of cyclical DBS on tremor control when compared to continuous stimulation.

Condition or Disease	Intervention/Treatment	Phase
Essential Tremor	Device: Abbott St Jude Medical Infinity 7 neurostimulator	N/A

Detailed Description

This study is a prospective, randomized, double-blind cross-over trials. Patients will be randomized into two groups in a cross-over fashion to have either continuous or cyclical stimulation for a total of three months. Following this, the trial will be unblinded and open-label follow up will continue for another nine months. Device use as per standard practice continues after the end of the trial.

If the hypothesis is proven correct, this will provide proof of concept that cyclical stimulation for the treatment of essential tremor results in improved battery life, reduced number of operations for battery changes, reduction in stimulation side-effects and enhancing quality of life.

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 15 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Intervention Model Description: Patients will be randomized into 2 groups with either cyclical or continuous stimulation. Patients will cross-over to the 2nd mode of stimulation after 1 month and then continued on the preferred mode of stimulation for the 3rd month. Open label follow-up starts at this point and continues for another 9 months.Patients will be randomized into 2 groups with either cyclical or continuous stimulation. Patients will cross-over to the 2nd mode of stimulation after 1 month and then continued on the preferred mode of stimulation for the 3rd month. Open label follow-up starts at this point and continues for another 9 months.
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Masking Description: This study adopts a blind design. Only the programmer is aware of the randomisation details and the parameters will be kept separately in order to keep others blind about the intervention. Unblinding of the study will occur at the 3rd month of the study.
• Primary Purpose: Treatment
• Official Title: Cyclic Versus Continuous Deep Brain Stimulation in Essential Tremor
• Actual Study Start Date: Feb 25, 2020
• Anticipated Primary Completion Date: Dec 31, 2022
• Anticipated Study Completion Date: Dec 31, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cyclical Stimulation This group will undergo cyclical stimulation mode of stimulation	Device: Abbott St Jude Medical Infinity 7 neurostimulator; The stimulator has the capability to deliver both continuous and cyclical modes of stimulation which is being investigated in this study
Active Comparator: Continuous Stimulation This group will undergo the standard continuous mode of stimulation	Device: Abbott St Jude Medical Infinity 7 neurostimulator; The stimulator has the capability to deliver both continuous and cyclical modes of stimulation which is being investigated in this study

Outcome Measures

Primary Outcome Measures

1. Fahn-Tolosa-Marin Tremor Rating Scale - total score difference [6 months compared to baseline]

   Change in Fahn-Tolosa-Marin tremor rating scale at 6 months compared to baseline. Minimum score is 0 and maximum score is 84. Higher scores indicate worse tremor control

Secondary Outcome Measures

1. EuroQol five dimensions questionnaire (EQ-5D) difference [6 months post activation compared to baseline]

   The total score of EQ-5D questionnaire at 6 months compared to baseline. Each dimension of the questionnaire has a minimum score of 1 and a maximum score of 5. Higher composite scores indicate increased levels of perceived problems

2. Beck's Depression Index questionnaire difference [6 months post activation compared to baseline]

   The total score of Beck's Depression Index questionnaire at 6 months compared to baseline. The minimum score is 0 and maximum score is 63. Higher scores indicate increasing severity of depression

3. Quality of Life in Essential Tremor (QUEST) questionnaire difference [6 months post activation compared to baseline]

   The total score of Quality of Life in Essential Tremor questionnaire at 6 months compared to baseline. Minimum score is 0 and maximum score is 120 with higher scores indicating worse quality of life due to tremor

4. Satisfaction with Treatment (SWT) questionnaire difference [6 months post activation compared to baseline]

   The difference in Satisfaction with Treatment outcomes at 6 months compared to baseline

5. Clinical Global Impression of Change (CGI) difference [6 months post activation compared to baseline]

   The difference in Clinical Global Impression of change outcome at 6 months compared to baseline

6. Implantable Pulse Generator (IPG) power consumption and longevity [6 months compared to baseline]

   Total amount of implantable pulse generator consumption used compared between the 2 groups

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Participant is at least 18 years of age

2. Participant has confirmed diagnosis of medically-refractory essential tremor

3. Participant meets criteria for implantation of DBS system

4. Participant understands the study requirements and treatments procedures and provides informed consent before any study-specific tests or procedures are performed

Exclusion Criteria:

1. Participant meets any contraindications for implantation of DBS system

2. Participant is undergoing or has had previous thalamic stimulation either in a research trial or with a permanent implant

3. Participant is unwilling or unable to comply with all study required follow-up evaluations

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	King's College Hospital NHS Foundation Trust	London		United Kingdom	SE5 9RS

Sponsors and Collaborators

• King's College Hospital NHS Trust

Investigators

• Principal Investigator: Keyoumars Ashkan, MD, King's College Hospital NHS Trust

Study Documents (Full-Text)

None provided.

More Information

Publications

• Ferreira JJ, Mestre TA, Lyons KE, Benito-León J, Tan EK, Abbruzzese G, Hallett M, Haubenberger D, Elble R, Deuschl G; MDS Task Force on Tremor and the MDS Evidence Based Medicine Committee. MDS evidence-based review of treatments for essential tremor. Mov Disord. 2019 Jul;34(7):950-958. doi: 10.1002/mds.27700. Epub 2019 May 2. Review.
• Flora ED, Perera CL, Cameron AL, Maddern GJ. Deep brain stimulation for essential tremor: a systematic review. Mov Disord. 2010 Aug 15;25(11):1550-9. doi: 10.1002/mds.23195. Review.
• Hariz GM, Blomstedt P, Koskinen LO. Long-term effect of deep brain stimulation for essential tremor on activities of daily living and health-related quality of life. Acta Neurol Scand. 2008 Dec;118(6):387-94. doi: 10.1111/j.1600-0404.2008.01065.x. Epub 2008 Jul 8.
• Koller WC, Lyons KE, Wilkinson SB, Troster AI, Pahwa R. Long-term safety and efficacy of unilateral deep brain stimulation of the thalamus in essential tremor. Mov Disord. 2001 May;16(3):464-8.
• Paschen S, Forstenpointner J, Becktepe J, Heinzel S, Hellriegel H, Witt K, Helmers AK, Deuschl G. Long-term efficacy of deep brain stimulation for essential tremor: An observer-blinded study. Neurology. 2019 Mar 19;92(12):e1378-e1386. doi: 10.1212/WNL.0000000000007134. Epub 2019 Feb 20.
• Rehncrona S, Johnels B, Widner H, Törnqvist AL, Hariz M, Sydow O. Long-term efficacy of thalamic deep brain stimulation for tremor: double-blind assessments. Mov Disord. 2003 Feb;18(2):163-70.
• Tröster AI, Pahwa R, Fields JA, Tanner CM, Lyons KE. Quality of life in Essential Tremor Questionnaire (QUEST): development and initial validation. Parkinsonism Relat Disord. 2005 Sep;11(6):367-73.
• Wharen RE Jr, Okun MS, Guthrie BL, Uitti RJ, Larson P, Foote K, Walker H, Marshall FJ, Schwalb J, Ford B, Jankovic J, Simpson R, Dashtipour K, Phibbs F, Neimat JS, Stewart RM, Peichel D, Pahwa R, Ostrem JL; SJM DBS ET Study Group. Thalamic DBS with a constant-current device in essential tremor: A controlled clinical trial. Parkinsonism Relat Disord. 2017 Jul;40:18-26. doi: 10.1016/j.parkreldis.2017.03.017. Epub 2017 Mar 30.

• Responsible Party: King's College Hospital NHS Trust
• ClinicalTrials.gov Identifier: NCT04260971
• Other Study ID Numbers: KCH20-025; 270731
• First Posted: Feb 7, 2020
• Last Update Posted: Sep 2, 2021
• Last Verified: Sep 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by King's College Hospital NHS Trust: Essential Tremor; Deep Brain Stimulation
• Additional relevant MeSH terms: Tremor; Essential Tremor

Study Results

No Results Posted as of Sep 2, 2021