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

Not yet recruiting

• Conditions: Parkinson Disease

• Registration Number: NCT05579379
• Lead Sponsor: University Hospital Tuebingen

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.

Study Timeline

• Status Verified: 2022-10
• Study Start: 2022-10
• Study First Submitted: 2022-10-10
• Study First Submitted QC: 2022-10-10
• Study First Posted: 2022-10-13
• Last Update Submitted: 2022-10-14
• Last Update Posted: 2022-10-18
• Primary Completion: 2024-09
• Study Completion: 2024-09

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 20

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).

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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 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.
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 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.
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.