INfusion VErsus STimulation in Parkinson's Disease (INVEST)

• Cost effectiveness in costs per unit on PDQ-39 [ Time Frame: 12 months ]
  The costs per unit on the PDQ-39.
  
  
• Cost-utility in costs per QALY [ Time Frame: 12 months ]
  The costs per QALY. The EQ-5D will be applied as the utility measure.
  
  

• Change from Baseline in quality of life: changes on PDQ-39 at 12 months [ Time Frame: 12 months ]
  Parkinson's Disease Questionnaire-39
  
  
• Change from Baseline in quality of life: changes on EQ-5D [ Time Frame: 12 months ]
  EQ-5D questionnaire
  
  
• Change from Baseline in motor symptoms: score changes in off and on state on MDS-UPDRS [ Time Frame: 12 months ]
  MDS-UPDRS part 3, motor symptom diary, clinical dyskinesia rating scale
  
  
• Change from Baseline in motor symptoms: changes in off-state, on-state without dyskinesias, on-state without troublesome dyskinesias and on-state with troublesome dyskinesias [ Time Frame: 12 months ]
  measured with motor symptom diary
  
  
• Change from Baseline in motor symptoms: changes on clinical Dyskinesia Rating Scale [ Time Frame: 12 months ]
  clinical dyskinesia rating scale
  
  
• Change from Baseline in non-motor symptoms: changes on Non Motor Symptom Checklist [ Time Frame: 12 months ]
  Non Motor Symptom Checklist
  
  
• Change from Baseline in non-motor symptoms: changes on Rotterdam Symptom Checklist [ Time Frame: 12 months ]
  Rotterdam Symptom Checklist
  
  
• Change from Baseline in non-motor symptoms: changes on SCOPA-AUT [ Time Frame: 12 months ]
  SCOPA-AUT
  
  
• Change from Baseline in non-motor symptoms: changes on MDS-UPDRS part 2 [ Time Frame: 12 months ]
  MDS-UPDRS part 2
  
  
• Number of participants with adverse effects and description of adverse effects at 12 months [ Time Frame: 12 months ]
  
• Number of participants with complications and description of complications at 12 months [ Time Frame: 12 months ]
  
• Number of participants with treatment failure at 12 months [ Time Frame: 12 months ]
  
• Number of participants who stopped treatment at 12 months [ Time Frame: 12 months ]
  
• Number of participants with treatment cross-over at 12 months [ Time Frame: 12 months ]
  
• Change from Baseline in PD-medication (levodopa-equivalent dose) at 12 months [ Time Frame: 12 months ]
  levodopa-equivalent dose
  
  
• Change from Baseline in disability: change of Hoehn and Yahr stage [ Time Frame: 12 months ]
  Hoehn and Yahr stage
  
  
• Change from Baseline in functional health status: changes on AMC Linear Disability Score) [ Time Frame: 12 months ]
  The AMC Linear Disability Score
  
  
• Change from Baseline in patient satisfaction (questionnaire) [ Time Frame: 12 months ]
  questionnaire
  
  
• Change from Baseline in patients attitude to treatment on PRO-Likert Scale [ Time Frame: 12 months ]
  PRO-Likert Scale
  
  
• Change from Baseline in cognition: changes on Mattis Dementia Rating Score [ Time Frame: 12 months ]
  Neuropsychologic assessment: Mattis Dementia Rating Score
  
  
• Change from Baseline in cognition: changes on PD-CRS [ Time Frame: 12 months ]
  Neuropsychologic assessment: Parkinson's Disease- Cognitive Rating Scale
  
  
• Change from Baseline in language: changes on Boston Naming Test [ Time Frame: 12 months ]
  Neuropsychologic assessment: Dutch version of Boston Naming Test
  
  
• Change from Baseline in language: changes on letter fluency test [ Time Frame: 12 months ]
  Neuropsychologic assessment: Dutch version of letter fluency test
  
  
• Change from Baseline in intelligence: changes on WAIS IV [ Time Frame: 12 months ]
  Neuropsychologic assessment: WAIS IV
  
  
• Change from Baseline in intelligence: changes on Dutch Reading test for Adults [ Time Frame: 12 months ]
  Neuropsychologic assessment: Dutch Reading test for Adults
  
  
• Change from Baseline in memory: changes on 15 word test [ Time Frame: 12 months ]
  Neuropsychologic assessment: Dutch 15 word test
  
  
• Change from Baseline in memory: changes on Rivermead Behavioral Memory Test [ Time Frame: 12 months ]
  Neuropsychologic assessment: Rivermead Behavioral Memory Test
  
  
• Change from Baseline in attention and executive functions: changes on trail making test [ Time Frame: 12 months ]
  Neuropsychologic assessment: trail making test
  
  
• Change from Baseline in attention and executive functions: changes on Stroop test [ Time Frame: 12 months ]
  Neuropsychologic assessment: Stroop I, II, III
  
  
• Change from Baseline in complex visual perception: changes in judgement of line orientation [ Time Frame: 12 months ]
  Neuropsychologic assessment: judgement of line orientation test
  
  
• Change from Baseline in constructive skills: changes in ability to draw a Clock drawing [ Time Frame: 12 months ]
  Neuropsychologic assessment: Drawing of a clock
  
  
• Change from Baseline in psychiatric disease: changes in psychiatric examination [ Time Frame: 12 months ]
  psychiatric examination
  
  
• Change from Baseline in psychiatric disease: changes on MINI [ Time Frame: 12 months ]
  Mini International Neuropsychiatric Interview
  
  
• Change from Baseline in psychiatric disease: changes on Columbia Suicide Severity Rating Scale [ Time Frame: 12 months ]
  changes in Columbia Suicide Severity Rating Scale
  
  
• Change from Baseline in psychiatric disease: changes on Hamilton Anxiety Scale [ Time Frame: 12 months ]
  Hamilton Anxiety Scale
  
  
• Change from Baseline in psychiatric disease: changes on Hamilton Depression Scale [ Time Frame: 12 months ]
  Hamilton Depression Scale
  
  
• Medical and non-medical care costs [ Time Frame: 12 months ]
  calculation of the costs by means of iMCQ and iPCQ questionnaire
  
  
• Change from Baseline in caregiver burden [ Time Frame: 12 months ]
  questionnaire
  
  
• Change from Baseline in Compulsive Disorders (Parkinson's Disease Impulsive-Compulsive Disorders Questionnaire (QUIP) [ Time Frame: 12 Months ]
  Parkinson's Disease Impulsive-Compulsive Disorders Questionnaire (QUIP)
  
  
• Change from Baseline in apathy (Starkstein's Apathy Scale) [ Time Frame: 12 Months ]
  Starkstein's Apathy Scale
  
  

Rationale: Both Continuous intrajejunal Levodopa Infusion (CLI) and Deep Brain Stimulation (DBS) are accepted therapies for the treatment of advanced Parkinson's disease (PD). As directly comparative studies are lacking, it is unknown whether one of the therapies is more effective. Besides, CLI seems to be more expensive. To determine the optimal treatment in advanced PD, a comparative study of CLI and DBS is warranted.

Hypothesis: We hypothesize that CLI is a more expensive therapy in advanced PD than DBS and that the surplus in costs is not cost-effective with regard to benefits for the patient and caregivers in quality of life, PD symptoms and adverse events.

Objective: To realize a cost-effective treatment strategy in advanced PD. Study design: Prospective, randomized, open label multicentre trial, with two additional patient preference treatment arms ("patient preference randomized trial").

Study population: Patients with PD who, despite optimal pharmacological treatment, have severe response fluctuations, dyskinesias, painful dystonia, or bradykinesia. A total of 66 patients will be randomized, at least 120 patients will be included in the patient preference arms.

Intervention: Patients will be randomized to DBS or CLI. For DBS treatment, 2 electrodes will be implanted in the brain. The electrodes are connected to an implanted pulse generator, which will be placed subcutaneously in the subclavian area. For CLI treatment, a tube will be placed in the jejunum via a percutaneous endoscopic gastrostomy (PEG). This tube is connected to an external pump that delivers the levodopa-gel.

Main study parameters: There are 6 specified assessment visits: at baseline, and 1 week, 3, 6, 9, and 12 months after start of the study treatment. The primary health economic outcomes are the costs per unit on the PDQ-39 and the costs per QALY for the cost-effectiveness and cost-utility analyses, respectively. The EQ-5D will be applied as the utility measure. Among the secondary outcomes are quality of life, functional health, complications and adverse effects, use of care and perceptions of patients and neurologists regarding both treatments.