Clinical trial NCT02480803: INfusion VErsus STimulation in Parkinson's Disease
Official title: Treatment in Advanced Parkinson's Disease: Continuous Intrajejunal Levodopa INfusion VErsus Deep Brain STimulation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Parkinson's Disease
Keywords: Parkinson
Parkinson's Disease
Deep Brain Stimulation
levodopa-carbidopa
Duodopa
continuous intrajejunal infusion
Lead sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Sponsor class: OTHER
Collaborators: name: ZonMw: The Netherlands Organisation for Health Research and Development
First posted: 2015-06-25
Enrollment: 51
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized Clinical Trial
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* Idiopathic Parkinson's Disease with bradykinesia and at least two of the following signs; resting tremor, rigidity, and asymmetry;
* Despite optimal pharmacological treatment, at least one of the following symptoms: severe response fluctuations, dyskinesias, painful dystonia or bradykinesia;
* A life expectancy of at least two years.

Exclusion Criteria:

* Age below 18 years
* Previous PD-neurosurgery (e.g., DBS, pallidotomy, thalamotomy);
* Previous CLI (through a PEG-tube or Nasal Jejuna\| tube);
* Hoehn and Yahr stage 5 at the best moment during the day;
* Other severely disabling disease;
* Dementia or signs of severe cognitive impairment
* Psychosis;
* Current depression;
* Contraindications for DBS surgery, such as a physical disorder making surgery hazardous;
* Contraindications for PEG surgery such as interposed organs, ascites and oesophagogastric varices, or for Duodopa;
* Pregnancy, breastfeeding, and women of child bearing age not using a reliable method of contraception;
* No informed consent;
* Legally incompetent adults;

Primary outcomes:
measure: Cost effectiveness in costs per changed unit on PDQ-39
timeFrame: 12 months
measure: Cost-utility in costs per changed Quality Adjusted Life Year (QALY, years)
timeFrame: 12 months
Secondary outcomes:
measure: Quality of life (on PDQ-39)
timeFrame: 12, 24 and 36 months
measure: Quality of life (on EQ-5D)
timeFrame: 12, 24 and 36 months
measure: Motor symptoms
timeFrame: 12 and 36 months
measure: Motor symptoms: time in off and on-state
timeFrame: 12, 24 and 36 months
measure: Motor experiences of daily living
timeFrame: 12, 24 and 36 months
measure: Dyskinesia
timeFrame: 12 and 36 months
measure: PD-medication (levodopa-equivalent dose)
timeFrame: 12, 24 and 36 months
measure: Functional health status
timeFrame: 12, 24 and 36 months
measure: Non-motor symptoms (Non Motor Symptom Checklist)
timeFrame: 12, 24 and 36 months
measure: Non-motor symptoms (Rotterdam Symptom Checklist
timeFrame: 12, 24 and 36 months
measure: Non-motor symptoms (SCOPA-AUT)
timeFrame: 12, 24 and 36 months
measure: Disability
timeFrame: 12, 24 and 36 months
measure: Cognitive functioning
timeFrame: 12 and 36 months
measure: Cognitive functioning Mattis
timeFrame: 12 and 36 months
measure: Neuropsychologic functioning BNT
timeFrame: 12 and 36 months
measure: Neuropsychologic functioning Letter Fluency
timeFrame: 12 and 36 months
measure: Neuropsychologic functioning WAIS IV
timeFrame: 12 and 36 months
measure: Neuropsychologic functioning Reading
timeFrame: 12 and 36 months
measure: Neuropsychologic functioning Word Test
timeFrame: 12 and 36 months
measure: Neuropsychologic functioning Memory
timeFrame: 12 and 36 months
measure: Neuropsychologic functioning Trail making
timeFrame: 12 and 36 months
measure: Neuropsychologic functioning Color Word
timeFrame: 12 and 36 months
measure: Neuropsychologic functioning Line Orientation
timeFrame: 12 and 36 months
measure: Neuropsychologic functioning Clock
timeFrame: 12 and 36 months
measure: Psychiatric disease
timeFrame: 12 and 36 months
measure: Apathy
timeFrame: 12, 24 and 36 months
measure: Compulsive Disorders
timeFrame: 12, 24 and 36 months
measure: Anxiety
timeFrame: 12 and 36 months
measure: Depression
timeFrame: 12 and 36 months
measure: Suicidality
timeFrame: 12 and 36 months
measure: Adverse effects
timeFrame: 12, 24 and 36 months
measure: Complications and description of complications
timeFrame: 12, 24 and 36 months
measure: Stopping allocated treatment
timeFrame: 12, 24 and 36 months
measure: Treatment failure
timeFrame: 12, 24 and 36 months
measure: Treatment cross-over
timeFrame: 12, 24 and 36 months
measure: Patient satisfaction
timeFrame: 12, 24 and 36 months
measure: Patients attitude to treatment
timeFrame: 12, 24 and 36 months
measure: Medical costs
timeFrame: 12, 24 and 36 months
measure: Non-medical care costs
timeFrame: 12, 24 and 36 months
measure: Caregiver burden
timeFrame: 12, 24 and 36 months
Other outcomes:
Locations:
city: Amsterdam
country: Netherlands
facility: Academic Medical Center
state: Noord Holland
Study officials:
affiliation: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
name: Joke M Dijk, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: van Poppelen D, Sisodia V, de Haan RJ, Dijkgraaf MGW, Schuurman PR, Geurtsen GJ, Berk AEM, de Bie RMA, Dijk JM. Protocol of a randomized open label multicentre trial comparing continuous intrajejunal levodopa infusion with deep brain stimulation in Parkinson's disease - the INfusion VErsus STimulation (INVEST) study. BMC Neurol. 2020 Jan 31;20(1):40. doi: 10.1186/s12883-020-1621-y.