Trial document





This study has been imported from ClinicalTrials.gov without additional data checks.
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  DRKS00007526

Trial Description

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Title

One Pass thalamIc aNd subthalamIc stimulatiON

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Trial Acronym

OPINION

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URL of the Trial

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Brief Summary in Lay Language

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

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Brief Summary in Scientific Language

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 Versice™
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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Organizational Data

  •   DRKS00007526
  •   2014/11/17
  •   2014/11/03
  •   yes
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Secondary IDs

  •   NCT02288468  (ClinicalTrials.gov)
  •   P000568  (University Hospital Freiburg)
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Health Condition or Problem studied

  •   Parkinson's Disease
  •   G20 -  Parkinson disease
  •   R25.1 -  Tremor, unspecified
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Interventions/Observational Groups

  •   Device: Versice™ Deep Brain Stimulation System
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Characteristics

  •   Interventional
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  •   Randomized controlled trial
  •   Blinded
  •   patient/subject, assessor
  •   Active control
  •   Treatment
  •   Crossover
  •   N/A
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Primary Outcome

- 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

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Secondary Outcome

- 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
- 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)
- 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)
- 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
- Psychiatric assessments including C-SSRS, YMRS, MADRS and BIS-11; time frame: Screening, baseline, then every 3 months until month 10; Psychiatric assessments including Columbia Suicide Severity Rating Scale (C-SSRS), Young Mania Rating Scale (YMRS), Montgomery-Asberg Depression Scale (MADRS) and 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
- 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

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Countries of Recruitment

  •   Germany
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Locations of Recruitment

  •  
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Recruitment

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  •   2015/01/31
  •   18
  •   Monocenter trial
  •   National
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Inclusion Criteria

  •   Both, male and female
  •   35   Years
  •   75   Years
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Additional Inclusion Criteria

1. Male or female patients aged aged ≥ 35 and ≤ 75 years

2. Patients with Parkinson's disease according to the criteria of the British Brain
Bank. 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.

3. Disease duration > 4 years

4. PDQ-39 to be completed within 42 days prior surgery

5. Written informed consent

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Exclusion Criteria

1. Major Depression with suicidal thoughts or suicidal thoughts in history

2. Dementia (Mattis Dementia Rating Score ≤ 130)

3. Acute psychosis stated by a psychiatric physician

4. Nursing care at home

5. Unable to give written informed consent

6. Surgical contraindications

7. Medications that are likely to cause interactions in the opinion of the investigator

8. Known or persistent abuse of medication, drugs or alcohol

9. Persons who are in a relationship of dependence/employment with the sponsor or the
investigator

10. 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;

11. Current or planned pregnancy, nursing period

12. Contraindications according to device instructions or Investigator's Brochure:

- Diathermy (shortwave, microwave, and/or therapeutic ultrasound diathermy)

- Magnetic Resonance Imaging (MRI)

- Patient incapability

- Poor surgical risks

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Addresses

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    • University Hospital Freiburg
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    • Boston Scientific Corporation
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    • University Hospital Freiburg
    • Volker Coenen, MD 
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    • Volker Coenen, MD 
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Sources of Monetary or Material Support

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    • Bitte wenden Sie sich an den Sponsor / Please refer to primary sponsor
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Status

  •   Recruiting planned
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Trial Publications, Results and other Documents

  •   Hilker R, Benecke R, Deuschl G, Fogel W, Kupsch A, Schrader C, Sixel-Döring 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.; 19360386
  •   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.; 10084526
  •   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.; 12539209
  •   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.; 9400514
  •   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. Review.; 20680036
  •   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.; 15654041
  •   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. Erratum in: N Engl J Med. 2006 Sep 21;355(12):1289.; 16943402
  •   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. Review.; 18325819
  •   Coenen VA, Allert N, Paus S, Kronenbürger M, Urbach H, Mädler B. Modulation of the Cerebello-thalamo-cortical Network in Thalamic Deep Brain Stimulation for Tremor: A Diffusion Tensor Imaging Study. Neurosurgery. 2014 Aug 25. [Epub ahead of print]; 25161000
  •   LANCE JW, SCHWAB RS, PETERSON EA. Action tremor and the cogwheel phenomenon in Parkinson's disease. Brain. 1963 Mar;86:95-110.; 13928399
  •   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.; 18958389
  •   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. Review.; 21293165
  •   Coenen VA, Allert N, Mädler 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.; 21553318
  •   Coenen VA, Mädler 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. Erratum in: Neurosurgery. 2011 Jun;68(6):E1780-1.; 21242831
  •   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. Review.; 21069833
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The parameters in ClinicalTrials.gov and DRKS are not identical. Therefore the data import from ClinicalTrials.gov required adjustments. For full details please see the DRKS FAQs .
  •   2
  •   2014/11/16
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