INfusion VErsus STimulation in Parkinson's Disease (INVEST)

Study Description

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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. Secondary outcomes will be quality of life, neurological impairments, among others.

Condition or disease	Intervention/treatment	Phase
Parkinson's Disease	Drug: Continuous intrajejunal infusion of levodopa-carbidopa; Device: deep brain stimulation	Phase 4

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 6 specified assessment visits: at baseline, and 1 week, 3, 6, 9, and 12 months after start of the study treatment. The primary health economic outcomes are the costs per unit on the PDQ-39 and the costs per QALY for the cost-effectiveness and cost-utility analyses, respectively. The EQ-5D will be applied as the utility measure. Among the secondary outcomes are quality of life, functional health, complications and adverse effects, use of care and perceptions of patients and neurologists regarding both treatments.

Study Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	66 participants
Allocation:	Randomized
Intervention Model:	Single Group Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	Treatment in Advanced Parkinson's Disease: Continuous Intrajejunal Levodopa INfusion VErsus Deep Brain STimulation
Study Start Date :	December 2014
Estimated Primary Completion Date :	December 2018
Estimated Study Completion Date :	December 2018

Arms and Interventions

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Arm	Intervention/treatment
Active Comparator: continuous levodopa infusion; continuous intrajejunal infusion of levodopa-carbidopa	Drug: Continuous intrajejunal infusion of levodopa-carbidopa; Continuous delivery of levodopa-carbidopa intestinal gel through an intrajejunal percutaneous tube (Duodopa, CLI, CILI); Other Names: Duodopa infusion; Intestinal levodopa-carbidopa infusion
Active Comparator: deep brain stimulation; Bilateral deep brain stimulation (DBS) of the subthalamic nucleus (STN)	Device: deep brain stimulation; Bilateral deep brain stimulation (DBS) of the subthalamic nucleus (STN); Other Names: DBS; DBS-STN

Outcome Measures

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Primary Outcome Measures :

1. Cost effectiveness in costs per unit on PDQ-39 [ Time Frame: 12 months ]
   The costs per unit on the PDQ-39.
2. Cost-utility in costs per QALY [ Time Frame: 12 months ]
   The costs per QALY. The EQ-5D will be applied as the utility measure.

Secondary Outcome Measures :

1. Change from Baseline in quality of life: changes on PDQ-39 at 12 months [ Time Frame: 12 months ]
   Parkinson's Disease Questionnaire-39
2. Change from Baseline in quality of life: changes on EQ-5D [ Time Frame: 12 months ]
   EQ-5D questionnaire
3. Change from Baseline in motor symptoms: score changes in off and on state on MDS-UPDRS [ Time Frame: 12 months ]
   MDS-UPDRS part 3, motor symptom diary, clinical dyskinesia rating scale
4. Change from Baseline in motor symptoms: changes in off-state, on-state without dyskinesias, on-state without troublesome dyskinesias and on-state with troublesome dyskinesias [ Time Frame: 12 months ]
   measured with motor symptom diary
5. Change from Baseline in motor symptoms: changes on clinical Dyskinesia Rating Scale [ Time Frame: 12 months ]
   clinical dyskinesia rating scale
6. Change from Baseline in non-motor symptoms: changes on Non Motor Symptom Checklist [ Time Frame: 12 months ]
   Non Motor Symptom Checklist
7. Change from Baseline in non-motor symptoms: changes on Rotterdam Symptom Checklist [ Time Frame: 12 months ]
   Rotterdam Symptom Checklist
8. Change from Baseline in non-motor symptoms: changes on SCOPA-AUT [ Time Frame: 12 months ]
   SCOPA-AUT
9. Change from Baseline in non-motor symptoms: changes on MDS-UPDRS part 2 [ Time Frame: 12 months ]
   MDS-UPDRS part 2
10. Number of participants with adverse effects and description of adverse effects at 12 months [ Time Frame: 12 months ]
11. Number of participants with complications and description of complications at 12 months [ Time Frame: 12 months ]
12. Number of participants with treatment failure at 12 months [ Time Frame: 12 months ]
13. Number of participants who stopped treatment at 12 months [ Time Frame: 12 months ]
14. Number of participants with treatment cross-over at 12 months [ Time Frame: 12 months ]
15. Change from Baseline in PD-medication (levodopa-equivalent dose) at 12 months [ Time Frame: 12 months ]
    levodopa-equivalent dose
16. Change from Baseline in disability: change of Hoehn and Yahr stage [ Time Frame: 12 months ]
    Hoehn and Yahr stage
17. Change from Baseline in functional health status: changes on AMC Linear Disability Score) [ Time Frame: 12 months ]
    The AMC Linear Disability Score
18. Change from Baseline in patient satisfaction (questionnaire) [ Time Frame: 12 months ]
    questionnaire
19. Change from Baseline in patients attitude to treatment on PRO-Likert Scale [ Time Frame: 12 months ]
    PRO-Likert Scale
20. Change from Baseline in cognition: changes on Mattis Dementia Rating Score [ Time Frame: 12 months ]
    Neuropsychologic assessment: Mattis Dementia Rating Score
21. Change from Baseline in cognition: changes on PD-CRS [ Time Frame: 12 months ]
    Neuropsychologic assessment: Parkinson's Disease- Cognitive Rating Scale
22. Change from Baseline in language: changes on Boston Naming Test [ Time Frame: 12 months ]
    Neuropsychologic assessment: Dutch version of Boston Naming Test
23. Change from Baseline in language: changes on letter fluency test [ Time Frame: 12 months ]
    Neuropsychologic assessment: Dutch version of letter fluency test
24. Change from Baseline in intelligence: changes on WAIS IV [ Time Frame: 12 months ]
    Neuropsychologic assessment: WAIS IV
25. Change from Baseline in intelligence: changes on Dutch Reading test for Adults [ Time Frame: 12 months ]
    Neuropsychologic assessment: Dutch Reading test for Adults
26. Change from Baseline in memory: changes on 15 word test [ Time Frame: 12 months ]
    Neuropsychologic assessment: Dutch 15 word test
27. Change from Baseline in memory: changes on Rivermead Behavioral Memory Test [ Time Frame: 12 months ]
    Neuropsychologic assessment: Rivermead Behavioral Memory Test
28. Change from Baseline in attention and executive functions: changes on trail making test [ Time Frame: 12 months ]
    Neuropsychologic assessment: trail making test
29. Change from Baseline in attention and executive functions: changes on Stroop test [ Time Frame: 12 months ]
    Neuropsychologic assessment: Stroop I, II, III
30. Change from Baseline in complex visual perception: changes in judgement of line orientation [ Time Frame: 12 months ]
    Neuropsychologic assessment: judgement of line orientation test
31. Change from Baseline in constructive skills: changes in ability to draw a Clock drawing [ Time Frame: 12 months ]
    Neuropsychologic assessment: Drawing of a clock
32. Change from Baseline in psychiatric disease: changes in psychiatric examination [ Time Frame: 12 months ]
    psychiatric examination
33. Change from Baseline in psychiatric disease: changes on MINI [ Time Frame: 12 months ]
    Mini International Neuropsychiatric Interview
34. Change from Baseline in psychiatric disease: changes on Columbia Suicide Severity Rating Scale [ Time Frame: 12 months ]
    changes in Columbia Suicide Severity Rating Scale
35. Change from Baseline in psychiatric disease: changes on Hamilton Anxiety Scale [ Time Frame: 12 months ]
    Hamilton Anxiety Scale
36. Change from Baseline in psychiatric disease: changes on Hamilton Depression Scale [ Time Frame: 12 months ]
    Hamilton Depression Scale
37. Medical and non-medical care costs [ Time Frame: 12 months ]
    calculation of the costs by means of iMCQ and iPCQ questionnaire
38. Change from Baseline in caregiver burden [ Time Frame: 12 months ]
    questionnaire
39. Change from Baseline in Compulsive Disorders (Parkinson's Disease Impulsive-Compulsive Disorders Questionnaire (QUIP) [ Time Frame: 12 Months ]
    Parkinson's Disease Impulsive-Compulsive Disorders Questionnaire (QUIP)
40. Change from Baseline in apathy (Starkstein's Apathy Scale) [ Time Frame: 12 Months ]
    Starkstein's Apathy Scale

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

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;

Contacts and Locations

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Contacts

Contact: Daniel van Poppelen, MD	+31205663447	d.vanpoppelen@amc.uva.nl

Locations

Netherlands
Academic Medical Center	Recruiting
Amsterdam, Noord Holland, Netherlands, 1100ZZ
Contact: Daniel van Poppelen, MD 0031205663447 invest@amc.nl
Contact: Joke M Dijk, MD PhD 0031205669111 j.m.dijk@amc.nl

Sponsors and Collaborators

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

ZonMw: The Netherlands Organisation for Health Research and Development

Investigators

Principal Investigator:	Joke M Dijk, MD, PhD	Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

More Information

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Additional Information:

English version of Study Website 

Study Website 

Responsible Party:	J.M. Dijk, J.M. Dijk, MD, PhD, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
ClinicalTrials.gov Identifier:	NCT02480803 History of Changes
Other Study ID Numbers:	2014_336; 2014-004501-32 ( EudraCT Number )
First Posted:	June 25, 2015
Last Update Posted:	February 2, 2017
Last Verified:	January 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:	Undecided

Keywords provided by J.M. Dijk, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA):

Parkinson; Parkinson's Disease; Deep Brain Stimulation	levodopa-carbidopa; Duodopa; continuous intrajejunal infusion

Additional relevant MeSH terms:

Parkinson Disease; Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Neurodegenerative Diseases; Levodopa; Carbidopa; Carbidopa, levodopa drug combination	Antiparkinson Agents; Anti-Dyskinesia Agents; Dopamine Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Physiological Effects of Drugs; Aromatic Amino Acid Decarboxylase Inhibitors; Enzyme Inhibitors; Adjuvants, Immunologic; Immunologic Factors; Dopamine Agonists