INfusion VErsus STimulation in Parkinson's Disease (INVEST)

Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Status and phase: Completed; Phase 4

Conditions: Parkinson's Disease

Treatments: Device: deep brain stimulation; Drug: Continuous intrajejunal infusion of levodopa-carbidopa

Study type: Interventional

Funder types: Other

Identifiers

NCT02480803

2014-004501-32 (EudraCT Number)

2014_336

Details and patient eligibility

About

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.

Full 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.

Enrollment: 51 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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;

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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51 participants in 2 patient groups

continuous levodopa infusion

Active Comparator group

Description:

continuous intrajejunal infusion of levodopa-carbidopa

Treatment:

Drug: Continuous intrajejunal infusion of levodopa-carbidopa

deep brain stimulation

Active Comparator group

Description:

Bilateral deep brain stimulation (DBS) of the subthalamic nucleus (STN)

Treatment:

Device: deep brain stimulation