Both Continuous intrajejunal Levodopa Infusion (CLI) and Deep Brain Stimulation (DBS) are accepted therapies for the treatment of advanced Parkinson's disease (PD). To date, no comparative studies have been executed. The INVEST study is an open label randomised controlled trial with cost-effectiveness as primary outcome. The main clinical outcome is quality of life; secondary outcomes are motor symptoms and neurological impairments, among others.
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 8 specified assessment visits: at baseline, and 1 week, 3, 6, 9, 12, 24 and 36 months after start of the study treatment. The primary health economic outcomes are the costs per changed unit on the PDQ-39 (and the costs per changed QALY for the cost-effectiveness and cost-utility analyses, respectively. The EQ-5D will be applied as the utility measure. Change in quality of life (expressed in the between group difference in change from baseline to 12 months on the PDQ-39 summary index score) is the main clinical outcome. Among the secondary outcomes are functional health, complications and adverse effects, use of care and perceptions of patients and neurologists regarding both treatments.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
51
Continuous delivery of levodopa-carbidopa intestinal gel through an intrajejunal percutaneous tube (Duodopa, CLI, CILI)
Bilateral deep brain stimulation (DBS) of the subthalamic nucleus (STN)
Academic Medical Center
Amsterdam, North Holland, Netherlands
Cost effectiveness in costs per changed unit on PDQ-39
The costs per changed unit on the PDQ-39.
Time frame: 12 months
Cost-utility in costs per changed Quality Adjusted Life Year (QALY, years)
The costs per QALY. The EuroQol 5D-3L (EQ-5D; 5 questions, each score 1-3, providing a health state, to be translated with provided Valuation set) will be applied as the utility measure.
Time frame: 12 months
Quality of life (on PDQ-39)
Changes from Baseline on Parkinson's Disease Questionnaire-39 (PDQ-39; score 0-100, higher score is lower quality of life)
Time frame: 12, 24 and 36 months
Quality of life (on EQ-5D)
Change from Baseline on EuroQol 5D-3L (EQ-5D; 5 questions, each score 1-3, providing a health state, to be translated with provided Valuation set)
Time frame: 12, 24 and 36 months
Motor symptoms
Score changes from Baseline in off and on state on Movement Disorder Society's Unified Parkinson Disease Rating Scale (MDS-UPDRS part 3; 0-132, high score is more motor symptoms)
Time frame: 12 and 36 months
Motor symptoms: time in off and on-state
Change from Baseline in time in off-state, on-state without dyskinesias, on-state without troublesome dyskinesias and on-state with troublesome dyskinesias measured with motor symptom diary
Time frame: 12, 24 and 36 months
Motor experiences of daily living
Changes from Baseline on MDS-UPDRS part 2 (Movement Disorder Society's Unified Parkinson Disease Rating Scale (MDS-UPDRS part 2; score 0-52, high score is more worse health)
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Time frame: 12, 24 and 36 months
Dyskinesia
Change from Baseline on clinical Dyskinesia Rating Scale (CDRS; score 0-28, high score is more dyskinesia)
Time frame: 12 and 36 months
PD-medication (levodopa-equivalent dose)
Change from Baseline expressed in levodopa-equivalent dose
Time frame: 12, 24 and 36 months
Functional health status
Change from Baseline on Amsterdam Linear Disability Score (ALDS, 29 items; 0-100, high score is high level of functional status)
Time frame: 12, 24 and 36 months
Non-motor symptoms (Non Motor Symptom Checklist)
Changes from Baseline on Non Motor Symptom Checklist
Time frame: 12, 24 and 36 months
Non-motor symptoms (Rotterdam Symptom Checklist
Change from Baseline on Rotterdam Symptom Checklist
Time frame: 12, 24 and 36 months
Non-motor symptoms (SCOPA-AUT)
Change from Baseline on SCOPA-AUT (SCales for Outcomes in PArkinson's Autonomic symptoms; score 0-92, higher score is more symptoms)
Time frame: 12, 24 and 36 months
Disability
Change from Baseline in Hoehn and Yahr stage (H\&Y stage; 1-5: a higher score is more disease progression)
Time frame: 12, 24 and 36 months
Cognitive functioning
Change from Baseline on Parkinson's Disease Cognition Rating Scale (PD-CRS; 0-134, higher score is a result of better cognitive performance)
Time frame: 12 and 36 months
Cognitive functioning Mattis
Change from Baseline in Mattis Dementia Rating score (score 0-144, higher score is better cognitive function)
Time frame: 12 and 36 months
Neuropsychologic functioning BNT
Change from Baseline in Boston Naming Test (range 0-30, higher is better)
Time frame: 12 and 36 months
Neuropsychologic functioning Letter Fluency
Change from Baseline in Letter Fluency (score 0-100, higher is better)
Time frame: 12 and 36 months
Neuropsychologic functioning WAIS IV
Change from Baseline in WAIS IV (Wechsler Adult Intelligence Scale IV - subsection similarities; score 0-36, higher is better)
Time frame: 12 and 36 months
Neuropsychologic functioning Reading
Change from Baseline in Dutch Reading Test (0-100, higher is better)
Time frame: 12 and 36 months
Neuropsychologic functioning Word Test
Change from Baseline in 15 word test (0-75, higher is better)
Time frame: 12 and 36 months
Neuropsychologic functioning Memory
Change from Baseline in Rivermead Behavioral memory test (subsection stores; score 0-42, higher is better)
Time frame: 12 and 36 months
Neuropsychologic functioning Trail making
Change from Baseline in Trail making test (score 10-500, higher score is longer time, i.e. worse score)
Time frame: 12 and 36 months
Neuropsychologic functioning Color Word
Change from Baseline in Stroop Color Word Test (score 10-1000, higher is better)
Time frame: 12 and 36 months
Neuropsychologic functioning Line Orientation
Change from Baseline in Judgement of line orientation (score 0-30, higher is better)
Time frame: 12 and 36 months
Neuropsychologic functioning Clock
Change from Baseline in Clock construction (score 0-14, higher is better)
Time frame: 12 and 36 months
Psychiatric disease
Change from Baseline in Mini International Neuropsychiatric Interview
Time frame: 12 and 36 months
Apathy
Change from Baseline in Starkstein's Apathy Scale (SAS; score 0-42, high score is more signs of apathy)
Time frame: 12, 24 and 36 months
Compulsive Disorders
Change in presence of Compulsive Disorder from Baseline assessed with Parkinson's Disease Impulsive-Compulsive Disorders Questionnaire (QUIP, utilizing established thresholds)
Time frame: 12, 24 and 36 months
Anxiety
Changes from Baseline on Hamilton Anxiety Scale (HAM-A; 0-56, high score is worse outcome)
Time frame: 12 and 36 months
Depression
Change from Baseline on Hamilton Depression Rating Scale (HDRS; 0-68, higher score is worse outcome)
Time frame: 12 and 36 months
Suicidality
Changes from Baseline on Columbia Suicide Severity Rating Scale (range 0-25, higher score is worse outcome)
Time frame: 12 and 36 months
Adverse effects
Number of participants with adverse effects and description of these
Time frame: 12, 24 and 36 months
Complications and description of complications
Number of participants with complications and description of these
Time frame: 12, 24 and 36 months
Stopping allocated treatment
Number of participants who stopped treatment
Time frame: 12, 24 and 36 months
Treatment failure
Number of participants with treatment failure
Time frame: 12, 24 and 36 months
Treatment cross-over
Number of participants with treatment cross-over
Time frame: 12, 24 and 36 months
Patient satisfaction
Descriptive questionnaire, no scale applied, descriptive statistics
Time frame: 12, 24 and 36 months
Patients attitude to treatment
Change from Baseline on Patient Reported Outcome Scale (range 0-128, high score is worse outcome)
Time frame: 12, 24 and 36 months
Medical costs
Calculation of the total costs in euro by means of iMCQ (iMTA Medical Consumption Questionnaire)
Time frame: 12, 24 and 36 months
Non-medical care costs
Calculation of the total costs in euro by means of iPCQ (iMTA Productivity Cost Questionnaire)
Time frame: 12, 24 and 36 months
Caregiver burden
Descriptive questionnaire, no scale applied, descriptive statistics
Time frame: 12, 24 and 36 months