DESENSITIZE-PD: Intestinal Levodopa + Entacapone Therapy (Lecigon®) to Support Dopaminergic Desensitization in Parkinson's Disease
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 20
- 主要终点
- Ardouin Behavioural Scale
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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).
排除标准
- •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).
结局指标
主要结局
Ardouin Behavioural Scale
时间窗: 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.
次要结局
- Questionnaire for impulsive-compulsive disorders in Parkinson's disease (QUIP)(At baseline, 3 months, 6 months and 12 months, respectively)
- Apathy Evaluation Scale(At baseline, 3 months, 6 months and 12 months, respectively)
- Movement Disorders Society -Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part IV(At baseline, 3 months, 6 months and 12 months, respectively)
- Neuropsychiatric Fluctuation Scale(At baseline, 3 months, 6 months and 12 months, respectively)
- Movement Disorders Society -Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III(At baseline, 3 months, 6 months and 12 months, respectively)
- Unified Dyskinesia Rating Scale (UDyRS)(At baseline, 3 months, 6 months and 12 months, respectively)
研究者
Daniel Weiss
Prof. Dr.
University Hospital Tuebingen