Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Dual Lead Thalamic Deep Brain Recording (DBR)-DBS Interface for Closed Loop Control of Severe Essential Tremor

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04212780
Recruitment Status : Recruiting
First Posted : December 30, 2019
Last Update Posted : September 16, 2020
Sponsor:
Collaborators:
National Institute of Neurological Disorders and Stroke (NINDS)
Medtronic
Information provided by (Responsible Party):
University of Florida

Tracking Information
First Submitted Date  ICMJE December 19, 2019
First Posted Date  ICMJE December 30, 2019
Last Update Posted Date September 16, 2020
Actual Study Start Date  ICMJE December 24, 2019
Estimated Primary Completion Date November 30, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 24, 2019)
Efficacy Assessment - Tremor [ Time Frame: Up to 24 months ]
Tremor rating scale This 5-point scale rates tremor severity based on tremor amplitude, from 0 (no tremor) to 4 (severe tremor) in each part of the body, and includes assessments of specific abilities and functional disability.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Dual Lead Thalamic Deep Brain Recording (DBR)-DBS Interface for Closed Loop Control of Severe Essential Tremor
Official Title  ICMJE Dual Lead Thalamic DBR-DBS Interface for Closed Loop Control of Severe Essential Tremor
Brief Summary This is a feasibility study based on physician-initiated Investigational Device Exemption (IDE) including intraoperative experiments and chronic testing of implanted dual thalamic DBS lead systems. This study will inform protocols for optimal use of implanted next-gen DBS systems for primarily tremor control in refractory essential tremor.If the approach appears to be successful, the pilot data generated will be used to base a future pivotal trial for FDA approval for enhanced tremor control and adaptive DBS (aDBS) functionality of DBS systems.
Detailed Description

Ventralis intermedius nucleus of the thalamus (VIM) Deep Brain Stimulation (DBS) has emerged as a highly effective treatment for essential tremor, which is an incurable, degenerative brain disorder that results in progressively debilitating tremor, afflicting an estimated 7 million people in the US (2.2% of the population). Clinical observation shows, however, that disease progression results in eventual recurrence of debilitating tremor in 10 to 20% of VIM DBS patients. DBS revision surgery, with replacement of sub-optimally positioned VIM DBS leads and addition of an ipsilateral ventralis oralis (VO) DBS lead, has emerged as an effective rescue strategy for many such patients with delayed failure of VIM DBS therapy.

Since essential tremors are typically not continuous, tremor suppressing DBS therapy need not necessarily be delivered continuously and could theoretically be effective if delivered only when movement intent or tremor is present.

Our central hypothesis is that a VIM+VO DBS system capable of detecting the neurophysiologic markers of essential tremor (ET) associated with goal directed movements, and providing responsive dual lead thalamic stimulation in a targeted and personalized manner, would provide improved suppression of severe tremor, reduce adverse effects associated with continuous stimulation, and prolong the battery life of the implantable neurostimulator (INS), decreasing the frequency of surgical procedures necessary to replace devices with depleted batteries.

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Outcomes Assessor)
Primary Purpose: Device Feasibility
Condition  ICMJE Essential Tremor
Intervention  ICMJE
  • Device: Medtronic Summit Rechargable (RC)+S
    Dual channel closed-loop pulse generator with connection to both new DBS leads for deep stimulation of VIM vs VO
  • Procedure: ipsilateral thalamic (VIM+VO) DBS
    Implantation of two new ipsilateral thalamic (VIM+VO) DBS
  • Procedure: standard ET DBS
    Single Lead VIM
  • Procedure: ipsilateral VO
    second lead in the ipsilateral VO
Study Arms  ICMJE
  • Active Comparator: Treatment Naive
    Participants receiving Long-term stimulation of the thalamus via dual leads for Essential Tremor
    Interventions:
    • Device: Medtronic Summit Rechargable (RC)+S
    • Procedure: standard ET DBS
    • Procedure: ipsilateral VO
  • Active Comparator: Refractory Participants
    Patients with recurrent, debilitating intention tremor despite ongoing, optimized VIM DBS therapy
    Interventions:
    • Device: Medtronic Summit Rechargable (RC)+S
    • Procedure: ipsilateral thalamic (VIM+VO) DBS
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: December 24, 2019)
10
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE November 30, 2022
Estimated Primary Completion Date November 30, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Patient gives an informed consent.
  • Patient is over 21 years of age.
  • Patient is diagnosed with a postural-intention (essential) tremor for at least 3 years, meets diagnostic criteria for ET, has been evaluated and examined by a movement disorders fellowship trained neurologist, and is being treated with traditional VIM DBS therapy.
  • Patient has no evidence of non-ET central nervous system disease or injury and has had a significantly disabling, upper extremity tremor despite ongoing VIM DBS therapy for at least three (3) months prior to DBS revision surgery.
  • Patient has a postural or kinetic tremor severity score of at least 2 out of 4 in the extremity intended for treatment on the Fahn-Tolosa-Marin Clinical Rating Scale for Tremor (TRS) despite ongoing VIM DBS therapy.
  • Patient has a TRS score of 2 or above in any one of the items 16-23 from the Disability subsection of the TRS: speaking, feeding other than liquids, bringing liquids to mouth, hygiene, dressing, writing, working and social activities despite ongoing VIM DBS therapy.
  • Patient's tremor is refractory to adequate trials of at least two medications, one of which should be either propranolol or primidone. An adequate medication trial is defined as a therapeutic dose of each medication or the development of side effects as the medication dose is titrated.
  • Patient is available for appropriate follow-up times for the length of the study

Exclusion Criteria:

  • Any previous neurosurgical intervention other than VIM DBS, including ablative brain lesions for tremor suppression.
  • Medication related movement disorders.
  • Any suspicion of Parkinson's disease, including presence of Parkinsonian features such as bradykinesia, rigidity, or postural instability.
  • Any behaviors consistent with alcohol or substance abuse as defined by the criteria outlined in Diagnostic and Statistical Manual of Mental Disorders (DSM-V).
  • Severe medical co-morbidity including cardiovascular disorder, lung disorder, kidney disease, continuous neurological disease, hematological disease, or frailty that impact tolerability of the surgery as judged by the screening physicians.
  • Abnormal brain MRI including hydrocephalus, stroke, structural lesions, demyelinating lesions, or infectious lesions. Also excluded will be subjects with severe brain atrophy.
  • Any uncontrolled symptoms or signs of increased intracranial pressure (e.g., headache, nausea, vomiting, lethargy, papilledema).
  • A history of seizures within the past year.
  • A dementia rating scale score (DRS) <130 signifying significant cognitive dysfunction and a potential for inability to cooperate with tasks involved in the study.
  • Any attempt or intent of suicide during the previous six months.
  • Presence or history of psychosis.
  • Significant or active mood disorders including depression. For the purpose of this study, we consider a significant mood disorder to include any subject who has:

    • Scores ≥ 20 on the Patient Health Questionnaire - 9 (PHQ-9).
    • Currently under the care of a psychiatrist
    • Currently participating in cognitive-behavioral therapy
    • Been hospitalized for the treatment of a psychiatric illness within 12 months
    • Ever received transcranial magnetic stimulation
    • Ever received electroconvulsive therapy
  • In addition, patients who are pregnant or plan to become pregnant will be excluded from this study.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 21 Years to 99 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE
Contact: Cami Swartz 352-733-2429 cami.swartz@neurology.ufl.edu
Contact: Karim Oweiss, PhD 352-294-1898 koweiss@ufl.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04212780
Other Study ID Numbers  ICMJE IRB201901021
OCR29622 ( Other Identifier: University of Florida )
1UH3NS109845-01 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: Yes
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party University of Florida
Study Sponsor  ICMJE University of Florida
Collaborators  ICMJE
  • National Institute of Neurological Disorders and Stroke (NINDS)
  • Medtronic
Investigators  ICMJE
Principal Investigator: Karin Oweiss, PhD University of Florida
PRS Account University of Florida
Verification Date September 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP