desensitize-pd: intestinal levodopa + entacapone therapy (lecigon®) to support dopaminergic desensitization in pd

Conditions: Parkinson Disease

Summary: 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.

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.

Eligibility criteria:
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).

Keywords: parkinson's disease dopaminergic sensitization hyperdopaminergic complications neuropsychiatric complications intestinal l-dopa therapy