INfusion VErsus STimulation in Parkinson's Disease

Parkinson's Disease Clinical Trial

— INVEST  

Official title:

Treatment in Advanced Parkinson's Disease: Continuous Intrajejunal Levodopa INfusion VErsus Deep Brain STimulation

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02480803
• Other study ID #: 2014_336
• Secondary ID: 2014-004501-32
• Status: Completed
• Phase: Phase 4
• Start date: December 19, 2014
• Est. completion date: January 26, 2024

Study information

• Verified date: February 2024
• Source: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 51
• Est. completion date: January 26, 2024
• Est. primary completion date: December 7, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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;

Related Conditions & MeSH terms

• Parkinson Disease
• Parkinson's Disease

Intervention

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

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

Locations

Country	Name	City	State
Netherlands	Academic Medical Center	Amsterdam	Noord Holland

Sponsors (2)

Lead Sponsor	Collaborator
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)	ZonMw: The Netherlands Organisation for Health Research and Development

Country where clinical trial is conducted

Netherlands, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cost effectiveness in costs per changed unit on PDQ-39	The costs per changed unit on the PDQ-39.	12 months
Primary	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.	12 months
Secondary	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)	12, 24 and 36 months
Secondary	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)	12, 24 and 36 months
Secondary	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)	12 and 36 months
Secondary	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	12, 24 and 36 months
Secondary	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)	12, 24 and 36 months
Secondary	Dyskinesia	Change from Baseline on clinical Dyskinesia Rating Scale (CDRS; score 0-28, high score is more dyskinesia)	12 and 36 months
Secondary	PD-medication (levodopa-equivalent dose)	Change from Baseline expressed in levodopa-equivalent dose	12, 24 and 36 months
Secondary	Functional health status	Change from Baseline on Amsterdam Linear Disability Score (ALDS, 29 items; 0-100, high score is high level of functional status)	12, 24 and 36 months
Secondary	Non-motor symptoms (Non Motor Symptom Checklist)	Changes from Baseline on Non Motor Symptom Checklist	12, 24 and 36 months
Secondary	Non-motor symptoms (Rotterdam Symptom Checklist	Change from Baseline on Rotterdam Symptom Checklist	12, 24 and 36 months
Secondary	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)	12, 24 and 36 months
Secondary	Disability	Change from Baseline in Hoehn and Yahr stage (H&Y stage; 1-5: a higher score is more disease progression)	12, 24 and 36 months
Secondary	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)	12 and 36 months
Secondary	Cognitive functioning Mattis	Change from Baseline in Mattis Dementia Rating score (score 0-144, higher score is better cognitive function)	12 and 36 months
Secondary	Neuropsychologic functioning BNT	Change from Baseline in Boston Naming Test (range 0-30, higher is better)	12 and 36 months
Secondary	Neuropsychologic functioning Letter Fluency	Change from Baseline in Letter Fluency (score 0-100, higher is better)	12 and 36 months
Secondary	Neuropsychologic functioning WAIS IV	Change from Baseline in WAIS IV (Wechsler Adult Intelligence Scale IV - subsection similarities; score 0-36, higher is better)	12 and 36 months
Secondary	Neuropsychologic functioning Reading	Change from Baseline in Dutch Reading Test (0-100, higher is better)	12 and 36 months
Secondary	Neuropsychologic functioning Word Test	Change from Baseline in 15 word test (0-75, higher is better)	12 and 36 months
Secondary	Neuropsychologic functioning Memory	Change from Baseline in Rivermead Behavioral memory test (subsection stores; score 0-42, higher is better)	12 and 36 months
Secondary	Neuropsychologic functioning Trail making	Change from Baseline in Trail making test (score 10-500, higher score is longer time, i.e. worse score)	12 and 36 months
Secondary	Neuropsychologic functioning Color Word	Change from Baseline in Stroop Color Word Test (score 10-1000, higher is better)	12 and 36 months
Secondary	Neuropsychologic functioning Line Orientation	Change from Baseline in Judgement of line orientation (score 0-30, higher is better)	12 and 36 months
Secondary	Neuropsychologic functioning Clock	Change from Baseline in Clock construction (score 0-14, higher is better)	12 and 36 months
Secondary	Psychiatric disease	Change from Baseline in Mini International Neuropsychiatric Interview	12 and 36 months
Secondary	Apathy	Change from Baseline in Starkstein's Apathy Scale (SAS; score 0-42, high score is more signs of apathy)	12, 24 and 36 months
Secondary	Compulsive Disorders	Change in presence of Compulsive Disorder from Baseline assessed with Parkinson's Disease Impulsive-Compulsive Disorders Questionnaire (QUIP, utilizing established thresholds)	12, 24 and 36 months
Secondary	Anxiety	Changes from Baseline on Hamilton Anxiety Scale (HAM-A; 0-56, high score is worse outcome)	12 and 36 months
Secondary	Depression	Change from Baseline on Hamilton Depression Rating Scale (HDRS; 0-68, higher score is worse outcome)	12 and 36 months
Secondary	Suicidality	Changes from Baseline on Columbia Suicide Severity Rating Scale (range 0-25, higher score is worse outcome)	12 and 36 months
Secondary	Adverse effects	Number of participants with adverse effects and description of these	12, 24 and 36 months
Secondary	Complications and description of complications	Number of participants with complications and description of these	12, 24 and 36 months
Secondary	Stopping allocated treatment	Number of participants who stopped treatment	12, 24 and 36 months
Secondary	Treatment failure	Number of participants with treatment failure	12, 24 and 36 months
Secondary	Treatment cross-over	Number of participants with treatment cross-over	12, 24 and 36 months
Secondary	Patient satisfaction	Descriptive questionnaire, no scale applied, descriptive statistics	12, 24 and 36 months
Secondary	Patients attitude to treatment	Change from Baseline on Patient Reported Outcome Scale (range 0-128, high score is worse outcome)	12, 24 and 36 months
Secondary	Medical costs	Calculation of the total costs in euro by means of iMCQ (iMTA Medical Consumption Questionnaire)	12, 24 and 36 months
Secondary	Non-medical care costs	Calculation of the total costs in euro by means of iPCQ (iMTA Productivity Cost Questionnaire)	12, 24 and 36 months
Secondary	Caregiver burden	Descriptive questionnaire, no scale applied, descriptive statistics	12, 24 and 36 months