INfusion VErsus STimulation in Parkinson's Disease

NCT ID: NCT02480803

Last Updated: 2024-02-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 51 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-12-19
• Study Completion Date: 2024-01-26

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.

Conditions

Parkinson's Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

continuous levodopa infusion

continuous intrajejunal infusion of levodopa-carbidopa

Group Type: ACTIVE_COMPARATOR

Continuous intrajejunal infusion of levodopa-carbidopa

Intervention Type: DRUG

Continuous delivery of levodopa-carbidopa intestinal gel through an intrajejunal percutaneous tube (Duodopa, CLI, CILI)

deep brain stimulation

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

Group Type: ACTIVE_COMPARATOR

deep brain stimulation

Intervention Type: DEVICE

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

Interventions

Continuous intrajejunal infusion of levodopa-carbidopa

Continuous delivery of levodopa-carbidopa intestinal gel through an intrajejunal percutaneous tube (Duodopa, CLI, CILI)

Intervention Type: DRUG

deep brain stimulation

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

Intervention Type: DEVICE

Other Intervention Names

Duodopa infusion; Intestinal levodopa-carbidopa infusion; DBS; DBS-STN

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;

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

ZonMw: The Netherlands Organisation for Health Research and Development

OTHER

Sponsor Role: collaborator

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

OTHER

Sponsor Role: lead

Responsible Party

J.M. Dijk

J.M. Dijk, MD, PhD, Neurologist, Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Joke M Dijk, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

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

Locations

Academic Medical Center

Amsterdam, North Holland, Netherlands

Countries

Netherlands

References

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.

Reference Type: BACKGROUND

PMID: 32005175 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2014-004501-32

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

2014_336

Identifier Type: -

Identifier Source: org_study_id