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One Pass thalamIc aNd subthalamIc stimulatiON (OPINION)

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ClinicalTrials.gov Identifier: NCT02288468
Recruitment Status : Active, not recruiting
First Posted : November 11, 2014
Last Update Posted : November 13, 2017
Sponsor:
Collaborator:
Boston Scientific Corporation
Information provided by (Responsible Party):
Prof. Dr. Volker Arnd Coenen, University Hospital Freiburg

Brief Summary:
Randomised, active controlled, double blinded (patient and observer blinded), monocentric trial with three treatments, three periods and six treatment sequences allocated according to a Williams design

Condition or disease Intervention/treatment Phase
Parkinson's Disease Device: Vercise™ Deep Brain Stimulation System Not Applicable

Detailed Description:

Tremor is the most salient symptom of Parkinson's disease (IPS=idiopathic Parkinson syndrome). Other symptoms are bradykinesia, rigidity and postural instability. As much as 75% of patients with IPS show resting tremor. Initially, tremor is typically unilateral and only visible in stress situation. In the later stage of the disease it becomes bilateral. The OPINION trial aims at the investigation of a combined approach to thalamic/subthalamic deep brain stimulation (DBS) for the treatment of patients with tremor dominant IPS or patients with equivalent type IPS who perceive tremor to be their dominant symptom. The planned approach will for the first time allow for the direct comparison of each condition in a homogeneous patient population and will furthermore allow an intra-individual comparison of the different stimulation conditions (Ventral intermediate nucleus (Vim/DRT) - Subthalamic nucleus (STN) - Vim/DRT+STN) with the outcome parameter "quality of life".

Patients will be registered to the trial and will undergo screening procedures (for eligibility criteria please see Inclusion and Exclusion criteria). If the patient is eligible the Investigational Medical Device (IMD) will be implanted (which is the Vercise™ Deep Brain Stimulation System manufactured by Boston Scientific). After implantation the IMD will remain OFF for a period of 1 month.

1 month after implantation treatment will be started. Patients will be randomized to one of the following 3 treatment groups: Subthalamic nucleus (STN) or Ventral intermediate nucleus (Vim/DRT) or combined stimulation (Vim/DRT+STN). Patients will undergo all three treatment groups each lasting 3 months. The patient is blinded meaning that study patients will not know what kind of treatment (e.g. mode/region of stimulation) they receive.

10 months after implantation the final visit (end of study visit) will be performed. After end of the trial, further treatment will be performed at the Department of Stereotactic and Functional Neurosurgery in Freiburg (Germany) according to established guidelines. Devices will be monitored 3-6 monthly Patient's medications will be adjusted as to the level of best treatment adjunct to stimulation.

Study endpoints (e.g. quality of life) will be evaluated by a blinded rater. In addition, an external video rating will be performed.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 18 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double (Participant, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: One Pass thalamIc aNd subthalamIc stimulatiON
Actual Study Start Date : July 2015
Estimated Primary Completion Date : March 2020
Estimated Study Completion Date : August 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: STN

Deep Brain Stimulation of Nucleus subthalamicus with Vercise™ Deep Brain Stimulation System.

The STN will be typically reached with the most distal contacts of the DBS electrode (8 contact). Imaging studies (postop helical CT and re-fusion to planning MRI data) will allow for the identification of contacts located in the STN. We expect the STN to be typically covered by contacts 1-4 of the Vercise™ DBS lead. Typically, only the most superficial contacts (3,4) will be activated after a monopolar review of each contact. In this monopolar review the therapeutic widths of each contact will be tested for its effectiveness in tremor reduction, reduction of rigidity and bradykinesia. Typical settings will be: Frequency 130-180 Hz, pulse width 60-90 us, Amplitude 1-7 mA.

Device: Vercise™ Deep Brain Stimulation System

The Vercise™ DBS System includes a Stimulator with DBS Leads for unilateral or bilateral stimulation. There are also DBS Extensions that allow the DBS Leads mounted in the skull to be extended to reach the Stimulator implanted near the clavicle.

The rechargeable Vercise DBS System utilizes current steering across eight contacts per DBS Lead to provide precise positioning of stimulation. The Stimulator is controlled by a handheld Remote Control, and can be interfaced with a Clinician's Programmer using the Bionic Navigator™ Software. Periodically, the Stimulator battery must be replenished with an RF (radiofrequency) charging device provided in the Patient DBS Charging Kit.

Other Name: Vercise DBS

Experimental: Vim/DRT

Deep Brain Stimulation of Ventral intermediate nucleus with Vercise™ Deep Brain Stimulation System.

The thalamic target (Vim/DRT) will be typically reached with the proximal contacts. Imaging studies (postop helical CT and re-fusion to planning MRI data) will allow for the identification of contacts located the thalamic target. We expect the thalamic target to be typically covered by contacts 5-8 of the Vercise™ DBS lead. We will perform a monopolar review of each contact. In this monopolar review the therapeutic widths of each contact will be tested for its effectiveness in tremor reduction and the occurrence of side effects (typically capsular e.g. facial contraction). Typical settings will be: Frequency 130-180 Hz, pulse width 60-90 us, Amplitude 1-7 mA.

Device: Vercise™ Deep Brain Stimulation System

The Vercise™ DBS System includes a Stimulator with DBS Leads for unilateral or bilateral stimulation. There are also DBS Extensions that allow the DBS Leads mounted in the skull to be extended to reach the Stimulator implanted near the clavicle.

The rechargeable Vercise DBS System utilizes current steering across eight contacts per DBS Lead to provide precise positioning of stimulation. The Stimulator is controlled by a handheld Remote Control, and can be interfaced with a Clinician's Programmer using the Bionic Navigator™ Software. Periodically, the Stimulator battery must be replenished with an RF (radiofrequency) charging device provided in the Patient DBS Charging Kit.

Other Name: Vercise DBS

Experimental: STN+Vim/DRT

Combined Deep Brain Stimulation of Nucleus subthalamicus and Ventral intermediate nucleus with Vercise™ Deep Brain Stimulation System.

STN+Vim/DRT stimulation is essentially a combination of the previously described procedure.

Device: Vercise™ Deep Brain Stimulation System

The Vercise™ DBS System includes a Stimulator with DBS Leads for unilateral or bilateral stimulation. There are also DBS Extensions that allow the DBS Leads mounted in the skull to be extended to reach the Stimulator implanted near the clavicle.

The rechargeable Vercise DBS System utilizes current steering across eight contacts per DBS Lead to provide precise positioning of stimulation. The Stimulator is controlled by a handheld Remote Control, and can be interfaced with a Clinician's Programmer using the Bionic Navigator™ Software. Periodically, the Stimulator battery must be replenished with an RF (radiofrequency) charging device provided in the Patient DBS Charging Kit.

Other Name: Vercise DBS




Primary Outcome Measures :
  1. Change in PDQ-39 total score [ Time Frame: From baseline every 3 months up to 9 months ]
    Change in PDQ-39 total score from base value (i.e. mean value of screening and baseline visit) until end of each treatment (Vim/DRT-DBS, STN-DBS, combined STN+Vim/DRT-DBS) 3 months after start of each treatment up to 9 months


Secondary Outcome Measures :
  1. Change in FTMTRS [ Time Frame: From baseline every 3 months up to 9 months ]
    Change in Fahn-Tolosa-Marin Tremor Rating Scale (FTMTRS) every three months after start of each treatment (Vim/DRT-DBS, STN-DBS, combined STN+Vim/DRT-DBS) compared to base value (i.e. mean value of screening and baseline visit)recording at the tremor peak in tremor analysis

  2. Change in UPDRS motor score (part III, except items 20 & 21) [ Time Frame: From baseline every 3 months up to 9 months ]
    Change in Unified Parkinson's Disease Rating Scale (UPDRS) motor score (part III, except items 20 & 21) every three months after start of each treatment (Vim/DRT-DBS, STN-DBS, combined STN+Vim/DRT-DBS) compared to base value (i.e. mean value of screening and baseline visit)

  3. Change in UPDRS (part III, tremor subscore (items 20 & 21)) or total power of accelerometry recording at the tremor peak in tremor analysis [ Time Frame: From baseline every 3 months up to 9 months ]
    Change in UPDRS (part III, tremor subscore (items 20 & 21)) or total power of accelerometry recording at the tremor peak in tremor analysis every three months after start of each treatment (Vim/DRT-DBS, STN-DBS, combined STN+Vim/DRT-DBS) compared to base value (i.e. mean value of screening and baseline visit)

  4. Clinical Global Impression Scale (CGI-I) [ Time Frame: Screening, baseline, then every 3 months until month 10 ]
    Assessment of Clinical Global Impression Scale (CGI-I) at screening, at baseline (month 1) and then every three months after start of each treatment (Vim/DRT-DBS, STN-DBS, combined STN+Vim/DRT-DBS) until month 10

  5. Psychiatric assessment: C-SSRS [ Time Frame: Screening, baseline, then every 3 months until month 10 ]
    Psychiatric assessment: Columbia Suicide Severity Rating Scale (C-SSRS) at screening, at baseline (month 1) and then every three months after start of each treatment (Vim/DRT-DBS, STN-DBS, combined STN+Vim/DRT-DBS) until month 10

  6. Psychiatric assessment: YMRS [ Time Frame: Screening, baseline, then every 3 months until month 10 ]
    Psychiatric assessment: Young Mania Rating Scale (YMRS) at screening, at baseline (month 1) and then every three months after start of each treatment (Vim/DRT-DBS, STN-DBS, combined STN+Vim/DRT-DBS) until month 10

  7. Psychiatric assessment: MADRS [ Time Frame: Screening, baseline, then every 3 months until month 10 ]
    Psychiatric assessment: Montgomery-Asberg Depression Scale (MADRS) at screening, at baseline (month 1) and then every three months after start of each treatment (Vim/DRT-DBS, STN-DBS, combined STN+Vim/DRT-DBS) until month 10

  8. Psychiatric assessment: BIS-11 [ Time Frame: Screening, baseline, then every 3 months until month 10 ]
    Psychiatric assessment: Barratt Impulsiveness Scale (BIS-11) at screening, at baseline (month 1) and then every three months after start of each treatment (Vim/DRT-DBS, STN-DBS, combined STN+Vim/DRT-DBS) until month 10

  9. Assessment of (Serious) Adverse Events related to Investigational Medical Device, surgical procedures, stimulation settings and/or changes to medication [ Time Frame: Starting from implantation of device until last visit at month 10 ]
    Assessment of Adverse Events (AEs) and Serious Adverse Events (SAEs) related to Investigational Medical Device (IMD), surgical procedures, stimulation settings and/or surgical procedures



Information from the National Library of Medicine

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Ages Eligible for Study:   35 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Male or female patients aged ≥ 35 and ≤ 75 years with a life expectancy of at least 5 years
  2. Patients with Parkinson's disease according to the criteria of the British Brain Bank as diagnosed by an in movement disorder specialized neurologist
  3. Parkinson patients are included with a medical treatment resistant and disabling resting and/or postural tremor as their major complaint and with a less prominent or absent hypokinetic-rigid component of their disease.
  4. Absence of postural instability (which would be aggravated under STN DBS)
  5. Hoehn & Yahr stage 1-3. After stadium 3 patients will show increased incidence of falling that can be aggravated by (typical) STN DBS
  6. Disease duration for at least 2 years and routine DAT-scan shows clear indication for Parkinsonism and atypical Parkinson syndromes are ruled out by routine glucose (FDG) PET
  7. PDQ-39 to be completed within 42 days prior surgery
  8. Written informed consent

Exclusion Criteria:

  1. Major Depression with suicidal thoughts
  2. Dementia (Mattis Dementia Rating Score ≤ 130)
  3. Patients with lifetime primary psychotic disorder, schizophrenia, or schizoaffective disorder
  4. Patients with acute psychosis as diagnosed by a psychiatrist
  5. Nursing care at home
  6. Unable to give written informed consent
  7. Surgical contraindications like deformed or displaced or not discernable target region, scarring after brain disease (infarction), need for continuous anticoagulation that cannot be bridged in order to obtain normal coagulation
  8. Patients with advanced stage cardiovascular disease
  9. Patients under immunosuppressive or chemotherapy because of malignant disease
  10. Patients who had previous intracranial surgery
  11. Patients who are already under DBS therapy
  12. Patients with aneurysm clips
  13. Patients with cochlear implants
  14. Simultaneous participation or previous participation within 30 days prior to start of screening in a clinical trial involving investigational medicinal product(s) or investigational medical device(s)
  15. Medications that are likely to cause interactions in the opinion of the investigator
  16. Known or persistent abuse of medication, drugs or alcohol
  17. Persons who are in a relationship of dependence/employment with the sponsor or the investigator
  18. Fertile women not using adequate contraceptive methods: female condoms, diaphragm or coil, each used in combination with spermicides; intra-uterine device; hormonal contraception in combination with a mechanical method of contraception;
  19. Current or planned pregnancy, nursing period
  20. Contraindications according to device instructions or Investigator's Brochure:

    • Diathermy: Shortwave, microwave, and/or therapeutic ultrasound diathermy. The energy generated by diathermy can be transferred to the Vercise™ DBS System, causing tissue damage at the contact site resulting in severe patient injury or death.
    • Magnetic Resonance Imaging (MRI): Patients implanted with the Vercise™ DBS System should not be subjected to MRI.
    • Patient incapability: Patients who are unable to properly operate the Remote Control and Charging System should not be implanted with the Vercise™ DBS System.
    • Poor surgical risks: The Vercise™ DBS System is not recommended for patients who - because of their primary disease or additional co-morbidities - are not likely to benefit from the DBS system implantation.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02288468


Locations
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Germany
University of Freiburg - Medical Center - Dept. of Stereotactic and Functional Neurosurgery
Freiburg, Germany, 79110
Sponsors and Collaborators
University Hospital Freiburg
Boston Scientific Corporation
Investigators
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Principal Investigator: Volker Coenen, MD University Hospital Freiburg

Publications:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Prof. Dr. Volker Arnd Coenen, Prof. Dr., University Hospital Freiburg
ClinicalTrials.gov Identifier: NCT02288468     History of Changes
Other Study ID Numbers: P000568
DRKS00007526 ( Registry Identifier: German Clinical Trials Register )
First Posted: November 11, 2014    Key Record Dates
Last Update Posted: November 13, 2017
Last Verified: November 2017

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Prof. Dr. Volker Arnd Coenen, University Hospital Freiburg:
Parkinson's Disease

Additional relevant MeSH terms:
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Parkinson Disease
Parkinsonian Disorders
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Movement Disorders
Neurodegenerative Diseases