Parkinson Disease
Conditions
Keywords
Parkinson's disease, dopaminergic sensitization, hyperdopaminergic complications, neuropsychiatric complications, intestinal L-Dopa therapy
Brief 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.
Detailed description
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.
Interventions
None listed
Sponsors
STADAPHARM GmbH
University Hospital Tuebingen
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Ardouin Behavioural Scale | At baseline, 3 months, 6 months and 12 months, respectively | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Questionnaire for impulsive-compulsive disorders in Parkinson's disease (QUIP) | At baseline, 3 months, 6 months and 12 months, respectively | To assess the severity of impulsive-compulsive disorders. Minimum value: 0, maximum value: 112, higher score means worse outcome. |
| Apathy Evaluation Scale | At baseline, 3 months, 6 months and 12 months, respectively | To quantify and characterize the apathy. Minimum value: 0, maximum value: 54, higher score means worse outcome. |
| Neuropsychiatric Fluctuation Scale | At baseline, 3 months, 6 months and 12 months, respectively | 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. |
| Movement Disorders Society -Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part IV | At baseline, 3 months, 6 months and 12 months, respectively | To measure the severity of motor complications. Minimum value: 0, maximum value: 24, higher score means worse outcome. |
| Unified Dyskinesia Rating Scale (UDyRS) | At baseline, 3 months, 6 months and 12 months, respectively | To evaluate involuntary movements. Minimum value: 0, maximum value: 104, higher score means worse outcome. |
| Movement Disorders Society -Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III | At baseline, 3 months, 6 months and 12 months, respectively | To measure the severity of Parkinson symptoms. Minimum value: 0, maximum value: 132, higher score means worse outcome. |
Contacts
Primary ContactDaniel T Weiss, MD
Backup ContactIdil Cebi, MD
Outcome results
None listed