DESENSITIZE-PD: Intestinal Levodopa + Entacapone Therapy (Lecigon®) to Support Dopaminergic Desensitization in PD

Study Overview
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Brief Summary
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20 patients with idiopathic Parkinson's disease, who are planned to undergo intestinal L-Dopa + entacapone (Lecigon®) treatment will be included into this observational single-armed study. These patient will be observed for hyperdopaminergic complications and neuropsychiatric fluctuations postprocedure at 3, 6 and 12 months.

Detailed Description
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This study is planned as non-interventional observational single-armed study in patients that are planned to undergo intestinal L-Dopa + entacapone (Lecigon®) treatment as regular treatment choice outside the study protocol and under the accepted regulatory approval and indication criteria (according to German Fachinformation Lecigon®). Patients will be observed at the pre-interventional baseline (oral treatment, before treatment initiation with Lecigon®), 3-month, 6-month follow-up, and final 12-month follow-up. As primary interest, the investigator will analyze the contrast of the pre-interventional baseline and 12-month follow-up in terms of the Ardouin Behavioural Scale which evaluates the hyperdopaminergic complications and neuropsychiatric fluctuations in a semi-structured interview. As additional exploratory outcomes, the investigator will study the Neuropsychiatric fluctuation scale, impulse control disorders with the QUIP rating scale (QUIP-RS). Moreover, the investigator will study apathy outcomes using the Apathy Evaluation Scale that mainly relates to the dopaminergic off-state. Outcomes of post-interventional apathy are particularly important, since i) they may coincide with hypodopaminergic off-states, and ii) since outcomes of postoperative apathy are a limitation of existing DBS therapy. Avoiding worsening of apathy might be a strength of intestinal L-Dopa therapy in this regard. Further, the investigator will study established measures of motor sensitization/de-sensitization in particular motor fluctuations and dyskinesia (MDS-UPDRS IV) and Unified Dyskinesia Rating Scale (UDysRS). For completeness, the investigator will characterize MDS-UPDRS III motor state in addition. Since dopaminergic desensitization occurs with considerable delay of rather weeks and months after changing oral to continuous treatment, the investigator expect a reduction of dopaminergic motor and neuropsychiatric complications within the first 6 months from introducing Lecigon® together with a stable course until final 12-month follow-up. The outcomes will be decided as contrast of the pre-interventional baseline (V0) in best oral treatment compared to 12 month follow-up of Lecigon® treatment.

Official Title
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DESENSITIZE-PD: Intestinal Levodopa + Entacapone Therapy (Lecigon®) to Support Dopaminergic Desensitization in Parkinson's Disease

Conditions
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Parkinson Disease

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written declaration of consent Age > 18 years and < 80 years Idiopathic Parkinson's syndrome (according to British Brain Bank criteria), including genetic forms L-dopa responsive Parkinson's syndrome Duration of disease > 5 years The treatment decision for Lecigon® was made as a regular treatment decision according to the established indication criteria outside the study Motor fluctuations on oral dopaminergic therapy with uncontrolled motor off symptoms Presence or history of dyskinesia based on available medical records or self-reported history History of dopaminergic neuropsychiatric therapy complications based on available physician's letters or self-reported history: impulse control disorders or dopamine dysregulation syndrome or off-condition apathy or affective response fluctuations or affective hypomanic or manic complications hyperdopaminergic behavioral complications (such as binge eating or hobbyism or punding or increased creativity or risk seeking behavior; analogous to Ardouin Behaviour Scale Chapter IV - hyperdopaminergic behaviors). Exclusion Criteria: Dementia according to ICD-10 criteria; mild cognitive impairment (MCI) according to screening tools such as MoCA or MMSE is not considered an exclusion criterion as long as ICD-10 criteria for dementia are not met regardless of MoCA/MMSE score. Acute paranoid psychosis or suicidality (however, impulse control disorder or dopamine dysregulation syndrome is not an exclusion criterion; illusions or (pseudo)-hallucinations are also not an exclusion criterion, as long as there is no risk to the patient or others according to clinical judgment; patients may be allowed to participate in the study after remission of the psychosis/suicidality) Pregnancy Contraindications to therapy with Lecigon® according the Summary of Product Characteristics (SmPC) Hypersensitivity to the active ingredients of Lecigon®. Narrow-angle glaucoma Severe heart failure Severe cardiac arrhythmia Acute stroke Severe impairment of liver function Non-selective MAO inhibitors and selective type A MAO inhibitors must not be used concomitantly with Lecigon®. These inhibitors must have been discontinued at least two weeks prior to starting treatment with Lecigon®. Lecigon® may be used concomitantly with the manufacturer's recommended dose of an MAO inhibitor with selectivity for MAO type B (e.g., selegiline hydrochloride) Conditions in which sympathomimetics (adrenergics) are contraindicated, e.g., pheochromocytoma, hyperthyroidism, and Cushing's syndrome. Previous malignant neuroleptic syndrome (NMS) and/or nontraumatic rhabdomyolysis. Suspected undiagnosed skin lesions or history of melanoma (levodopa could activate malignant melanoma).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ardouin Behavioural Scale | To evaluate the hyperdopaminergic complications and neuropsychiatric fluctuations from baseline to 12-months follow-up. Minimum value: 0, maximum value: 84, higher score means worse outcome. | At baseline, 3 months, 6 months and 12 months, respectively | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Neuropsychiatric Fluctuation Scale | To identify and quantify neuropsychiatric fluctuations during motor fluctuations. Minimum value for OFF items: 0, maximum value for OFF items: 30, higher score means worse outcome. Minimum value for ON items: 0, maximum value for ON items: 30, higher score means worse outcome. | At baseline, 3 months, 6 months and 12 months, respectively | 
| Questionnaire for impulsive-compulsive disorders in Parkinson's disease (QUIP) | To assess the severity of impulsive-compulsive disorders. Minimum value: 0, maximum value: 112, higher score means worse outcome. | At baseline, 3 months, 6 months and 12 months, respectively | 
| Apathy Evaluation Scale | To quantify and characterize the apathy. Minimum value: 0, maximum value: 54, higher score means worse outcome. | At baseline, 3 months, 6 months and 12 months, respectively | 
| Movement Disorders Society -Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III | To measure the severity of Parkinson symptoms. Minimum value: 0, maximum value: 132, higher score means worse outcome. | At baseline, 3 months, 6 months and 12 months, respectively | 
| Movement Disorders Society -Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part IV | To measure the severity of motor complications. Minimum value: 0, maximum value: 24, higher score means worse outcome. | At baseline, 3 months, 6 months and 12 months, respectively | 
| Unified Dyskinesia Rating Scale (UDyRS) | To evaluate involuntary movements. Minimum value: 0, maximum value: 104, higher score means worse outcome. | At baseline, 3 months, 6 months and 12 months, respectively | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Parkinson's disease, dopaminergic sensitization, hyperdopaminergic complications, neuropsychiatric complications, intestinal L-Dopa therapy