Clinical trial NCT02288468: One Pass thalamIc aNd subthalamIc stimulatiON
Official title: One Pass thalamIc aNd subthalamIc stimulatiON
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Parkinson's Disease
Keywords: Parkinson's Disease
Lead sponsor: University Hospital Freiburg
Sponsor class: OTHER
Collaborators: name: Boston Scientific Corporation
First posted: 2014-11-11
Enrollment: 12
Sex: ALL
Minimum age (years): 35
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.

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 of the randomized study will be performed. After that, patients will be asked to take part in an open label extension phase of the study where they will be treated unblinded according to established guidelines and according to their own preferred stimulation mode, just as they would be in a clinical routine setting. The extension phase is concluded by an end of study visit at 36 months after implantation.

After the 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.

Eligibility 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.

Primary outcomes:
measure: Change in PDQ-39 total score
timeFrame: From baseline every 3 months up to 9 months
Secondary outcomes:
measure: Change in FTMTRS
timeFrame: From baseline every 3 months up to 9 months, and at 36 months
measure: Change in UPDRS motor score (part III, except items 20 & 21)
timeFrame: From baseline every 3 months up to 9 months, and at 36 months
measure: Change in UPDRS (part III, tremor subscore (items 20 & 21)) or total power of accelerometry recording at the tremor peak in tremor analysis
timeFrame: From baseline every 3 months up to 9 months, and at 36 months
measure: Clinical Global Impression Scale (CGI-I)
timeFrame: Screening, baseline, then every 3 months until month 10, and at 36 months
measure: Change in PDQ-39 total score at 36 months
timeFrame: Baseline, month 36
measure: Psychiatric assessment: C-SSRS
timeFrame: Screening, baseline, then every 3 months until month 10, and at 36 months
measure: Psychiatric assessment: YMRS
timeFrame: Screening, baseline, then every 3 months until month 10, and at 36 months
measure: Psychiatric assessment: MADRS
timeFrame: Screening, baseline, then every 3 months until month 10, and at 36 months
measure: Psychiatric assessment: BIS-11
timeFrame: Screening, baseline, then every 3 months until month 10, and at 36 months
measure: Assessment of (Serious) Adverse Events related to Investigational Medical Device, surgical procedures, stimulation settings and/or changes to medication
timeFrame: Starting from implantation of device until last visit at month 36
Other outcomes:
Locations:
city: Freiburg
country: Germany
facility: University of Freiburg - Medical Center - Dept. of Stereotactic and Functional Neurosurgery
Study officials:
affiliation: University Hospital Freiburg
name: Volker Coenen, MD
role: PRINCIPAL_INVESTIGATOR
References:
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