One Pass thalamIc aNd subthalamIc stimulatiON

NCT02288468 | Completed

• 2 other identifiers: P000568DRKS00007526
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

Main part of the study: 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 Open Label Extension: After study treatment as described above, patients will be treated unblinded in their preferred stimulation mode until 36 months after implantation.

Conditions

Parkinson's Disease

Keywords

Parkinson's Disease

Outcome Measures

Primary Outcomes (1)

• Change in PDQ-39 total score

  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

  From baseline every 3 months up to 9 months

Secondary Outcomes (10)

• Change in FTMTRS

  From baseline every 3 months up to 9 months, and at 36 months

• Change in UPDRS motor score (part III, except items 20 & 21)

  From baseline every 3 months up to 9 months, and at 36 months

• Change in UPDRS (part III, tremor subscore (items 20 & 21)) or total power of accelerometry recording at the tremor peak in tremor analysis

  From baseline every 3 months up to 9 months, and at 36 months

• Clinical Global Impression Scale (CGI-I)

  Screening, baseline, then every 3 months until month 10, and at 36 months

• Change in PDQ-39 total score at 36 months

  Baseline, month 36

Study Arms (3)

STN

EXPERIMENTAL

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

Vim/DRT

EXPERIMENTAL

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

STN+Vim/DRT

EXPERIMENTAL

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

Interventions

Vercise™ Deep Brain Stimulation System DEVICE

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.

Also known as: Vercise DBS

STN; STN+Vim/DRT; Vim/DRT

Eligibility Criteria

• Age: 35 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female patients aged ≥ 35 and ≤ 75 years with a life expectancy of at least 5 years
• Patients with Parkinson's disease according to the criteria of the British Brain Bank as diagnosed by an in movement disorder specialized neurologist
• 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.
• Absence of postural instability (which would be aggravated under STN DBS)
• Hoehn \& Yahr stage 1-3. After stadium 3 patients will show increased incidence of falling that can be aggravated by (typical) STN DBS
• 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
• PDQ-39 to be completed within 42 days prior surgery
• Written informed consent

You may not qualify if:

• Major Depression with suicidal thoughts
• Dementia (Mattis Dementia Rating Score ≤ 130)
• Patients with lifetime primary psychotic disorder, schizophrenia, or schizoaffective disorder
• Patients with acute psychosis as diagnosed by a psychiatrist
• Nursing care at home
• Unable to give written informed consent
• 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
• Patients with advanced stage cardiovascular disease
• Patients under immunosuppressive or chemotherapy because of malignant disease
• Patients who had previous intracranial surgery
• Patients who are already under DBS therapy
• Patients with aneurysm clips
• Patients with cochlear implants
• 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)
• Medications that are likely to cause interactions in the opinion of the investigator

Sponsors & Collaborators

• University Hospital Freiburg: lead
• Boston Scientific Corporation: collaborator

Study Sites (1)

University of Freiburg - Medical Center - Dept. of Stereotactic and Functional Neurosurgery

Freiburg im Breisgau, 79110, Germany

Location

Related Publications (19)

• Hilker R, Benecke R, Deuschl G, Fogel W, Kupsch A, Schrader C, Sixel-Doring F, Timmermann L, Volkmann J, Lange M; German Deep Brain Stimulation Association. [Deep brain stimulation for Parkinson's disease. Consensus recommendations of the German Deep Brain Stimulation Association]. Nervenarzt. 2009 Jun;80(6):646-55. doi: 10.1007/s00115-009-2695-3. German.

  PMID: 19360386 BACKGROUND

• Limousin P, Speelman JD, Gielen F, Janssens M. Multicentre European study of thalamic stimulation in parkinsonian and essential tremor. J Neurol Neurosurg Psychiatry. 1999 Mar;66(3):289-96. doi: 10.1136/jnnp.66.3.289.

  PMID: 10084526 BACKGROUND

• Rehncrona S, Johnels B, Widner H, Tornqvist 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. doi: 10.1002/mds.10309.

  PMID: 12539209 BACKGROUND

• Krack P, Pollak P, Limousin P, Benazzouz A, Benabid AL. Stimulation of subthalamic nucleus alleviates tremor in Parkinson's disease. Lancet. 1997 Dec 6;350(9092):1675. doi: 10.1016/s0140-6736(97)24049-3. No abstract available.

  PMID: 9400514 BACKGROUND

• Volkmann J, Daniels C, Witt K. Neuropsychiatric effects of subthalamic neurostimulation in Parkinson disease. Nat Rev Neurol. 2010 Sep;6(9):487-98. doi: 10.1038/nrneurol.2010.111. Epub 2010 Aug 3.

  PMID: 20680036 BACKGROUND

• Fraix V, Pollak P, Moro E, Chabardes S, Xie J, Ardouin C, Benabid AL. Subthalamic nucleus stimulation in tremor dominant parkinsonian patients with previous thalamic surgery. J Neurol Neurosurg Psychiatry. 2005 Feb;76(2):246-8. doi: 10.1136/jnnp.2003.022707.

  PMID: 15654041 BACKGROUND

• Deuschl G, Schade-Brittinger C, Krack P, Volkmann J, Schafer H, Botzel K, Daniels C, Deutschlander A, Dillmann U, Eisner W, Gruber D, Hamel W, Herzog J, Hilker R, Klebe S, Kloss M, Koy J, Krause M, Kupsch A, Lorenz D, Lorenzl S, Mehdorn HM, Moringlane JR, Oertel W, Pinsker MO, Reichmann H, Reuss A, Schneider GH, Schnitzler A, Steude U, Sturm V, Timmermann L, Tronnier V, Trottenberg T, Wojtecki L, Wolf E, Poewe W, Voges J; German Parkinson Study Group, Neurostimulation Section. A randomized trial of deep-brain stimulation for Parkinson's disease. N Engl J Med. 2006 Aug 31;355(9):896-908. doi: 10.1056/NEJMoa060281.

  PMID: 16943402 BACKGROUND

• Okun MS, Rodriguez RL, Foote KD, Sudhyadhom A, Bova F, Jacobson C, Bello B, Zeilman P, Fernandez HH. A case-based review of troubleshooting deep brain stimulator issues in movement and neuropsychiatric disorders. Parkinsonism Relat Disord. 2008 Nov;14(7):532-8. doi: 10.1016/j.parkreldis.2008.01.001. Epub 2008 Mar 5.

  PMID: 18325819 BACKGROUND

• Coenen VA, Allert N, Paus S, Kronenburger M, Urbach H, Madler B. Modulation of the cerebello-thalamo-cortical network in thalamic deep brain stimulation for tremor: a diffusion tensor imaging study. Neurosurgery. 2014 Dec;75(6):657-69; discussion 669-70. doi: 10.1227/NEU.0000000000000540.

  PMID: 25161000 BACKGROUND

• LANCE JW, SCHWAB RS, PETERSON EA. Action tremor and the cogwheel phenomenon in Parkinson's disease. Brain. 1963 Mar;86:95-110. doi: 10.1093/brain/86.1.95. No abstract available.

  PMID: 13928399 BACKGROUND

• Coenen VA, Prescher A, Schmidt T, Picozzi P, Gielen FL. What is dorso-lateral in the subthalamic Nucleus (STN)?--a topographic and anatomical consideration on the ambiguous description of today's primary target for deep brain stimulation (DBS) surgery. Acta Neurochir (Wien). 2008 Nov;150(11):1163-5; discussion 1165. doi: 10.1007/s00701-008-0136-x. Epub 2008 Oct 29.

  PMID: 18958389 BACKGROUND

• Zrinzo L, Holl EM, Petersen EA, Limousin P, Foltynie T, Hariz MI. Skewering the subthalamic nucleus via a parietal approach. Stereotact Funct Neurosurg. 2011;89(2):70-5. doi: 10.1159/000323371. Epub 2011 Feb 2.

  PMID: 21293165 BACKGROUND

• Coenen VA, Allert N, Madler B. A role of diffusion tensor imaging fiber tracking in deep brain stimulation surgery: DBS of the dentato-rubro-thalamic tract (drt) for the treatment of therapy-refractory tremor. Acta Neurochir (Wien). 2011 Aug;153(8):1579-85; discussion 1585. doi: 10.1007/s00701-011-1036-z. Epub 2011 May 8.

  PMID: 21553318 BACKGROUND

• Coenen VA, Madler B, Schiffbauer H, Urbach H, Allert N. Individual fiber anatomy of the subthalamic region revealed with diffusion tensor imaging: a concept to identify the deep brain stimulation target for tremor suppression. Neurosurgery. 2011 Apr;68(4):1069-75; discussion 1075-6. doi: 10.1227/NEU.0b013e31820a1a20.

  PMID: 21242831 BACKGROUND

• Tomlinson CL, Stowe R, Patel S, Rick C, Gray R, Clarke CE. Systematic review of levodopa dose equivalency reporting in Parkinson's disease. Mov Disord. 2010 Nov 15;25(15):2649-53. doi: 10.1002/mds.23429.

  PMID: 21069833 BACKGROUND

• Patel DM, Walker HC, Brooks R, Omar N, Ditty B, Guthrie BL. Adverse events associated with deep brain stimulation for movement disorders: analysis of 510 consecutive cases. Neurosurgery. 2015 Mar;11 Suppl 2(Suppl 2):190-9. doi: 10.1227/NEU.0000000000000659.

  PMID: 25599204 BACKGROUND

• Deuschl G, Bain P, Brin M. Consensus statement of the Movement Disorder Society on Tremor. Ad Hoc Scientific Committee. Mov Disord. 1998;13 Suppl 3:2-23. doi: 10.1002/mds.870131303.

  PMID: 9827589 BACKGROUND

• Reinacher PC, Amtage F, Rijntjes M, Piroth T, Prokop T, Jenkner C, Katzler J, Coenen VA. One Pass Thalamic and Subthalamic Stimulation for Patients with Tremor-Dominant Idiopathic Parkinson Syndrome (OPINION): Protocol for a Randomized, Active-Controlled, Double-Blinded Pilot Trial. JMIR Res Protoc. 2018 Jan 30;7(1):e36. doi: 10.2196/resprot.8341.

  PMID: 29382631 DERIVED

• Coenen VA, Rijntjes M, Prokop T, Piroth T, Amtage F, Urbach H, Reinacher PC. One-pass deep brain stimulation of dentato-rubro-thalamic tract and subthalamic nucleus for tremor-dominant or equivalent type Parkinson's disease. Acta Neurochir (Wien). 2016 Apr;158(4):773-781. doi: 10.1007/s00701-016-2725-4. Epub 2016 Feb 15.

  PMID: 26876564 DERIVED

MeSH Terms

Conditions

Parkinson Disease

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases

Study Officials

• Volker Coenen, MD

  University Hospital Freiburg

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof. Dr.

Study Record Dates

• First Submitted: November 3, 2014
• First Posted: November 11, 2014
• Study Start: July 1, 2015
• Primary Completion: May 1, 2019
• Study Completion: November 18, 2020
• Last Updated: July 21, 2021

Record last verified: 2021-07

Locations

DE (1)