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

Sponsor

University Hospital Tuebingen (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05579379

Collaborator

STADAPHARM GmbH (Other)

Enrollment

Anticipated Duration (Months)

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Parkinson Disease

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.

Study Design

Study Type:

Observational

Anticipated Enrollment :

20 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

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

Anticipated Study Start Date :

Oct 1, 2022

Anticipated Primary Completion Date :

Sep 1, 2024

Anticipated Study Completion Date :

Sep 1, 2024

Outcome Measures

Primary Outcome Measures

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 Outcome Measures

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.
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.
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.
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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).