## Protocol Section
### Identification Module
**NCT ID:** NCT05579379

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

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

#### Organization Study ID Info
**ID:** 388/2022BO2
#### Organization
**Class:** OTHER
**Full Name:** University Hospital Tuebingen
### Status Module
#### Completion Date
**Date:** 2024-09

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2022-10-18

**Type:** ACTUAL

**Last Update Submit Date:** 2022-10-14

**Overall Status:** NOT_YET_RECRUITING

#### Primary Completion Date
**Date:** 2024-09

**Type:** ESTIMATED

#### Start Date
**Date:** 2022-10

**Type:** ESTIMATED

**Status Verified Date:** 2022-10

#### Study First Post Date
**Date:** 2022-10-13
**Type:** ACTUAL
**Study First Submit Date:** 2022-10-10
**Study First Submit QC Date:** 2022-10-10
### Sponsor Collaborators Module

#### Collaborators

**Class:** UNKNOWN

**Name:** STADAPHARM GmbH

#### Lead Sponsor

**Class:** OTHER

**Name:** University Hospital Tuebingen

#### Responsible Party

**Investigator Affiliation:** University Hospital Tuebingen

**Investigator Full Name:** Daniel Weiss

**Investigator Title:** Prof. Dr.

**Type:** PRINCIPAL_INVESTIGATOR

### Oversight Module

**Oversight Has DMC:** True

### Description Module

**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.

### Conditions Module

**Conditions:**

- Parkinson Disease

**Keywords:**

- Parkinson's disease

- dopaminergic sensitization

- hyperdopaminergic complications

- neuropsychiatric complications

- intestinal L-Dopa therapy

### Design Module

#### Design Info

**Observational Model:** COHORT

**Time Perspective:** PROSPECTIVE

#### Enrollment Info

**Count:** 20

**Type:** ESTIMATED

**Study Type:** OBSERVATIONAL

### Outcomes Module

#### Primary Outcomes

**Description:** 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.

**Measure:** Ardouin Behavioural Scale

**Time Frame:** At baseline, 3 months, 6 months and 12 months, respectively

#### Secondary Outcomes

**Description:** 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.

**Measure:** Neuropsychiatric Fluctuation Scale

**Time Frame:** At baseline, 3 months, 6 months and 12 months, respectively

**Description:** To assess the severity of impulsive-compulsive disorders. Minimum value: 0, maximum value: 112, higher score means worse outcome.

**Measure:** Questionnaire for impulsive-compulsive disorders in Parkinson's disease (QUIP)

**Time Frame:** At baseline, 3 months, 6 months and 12 months, respectively

**Description:** To quantify and characterize the apathy. Minimum value: 0, maximum value: 54, higher score means worse outcome.

**Measure:** Apathy Evaluation Scale

**Time Frame:** At baseline, 3 months, 6 months and 12 months, respectively

**Description:** To measure the severity of Parkinson symptoms. Minimum value: 0, maximum value: 132, higher score means worse outcome.

**Measure:** Movement Disorders Society -Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III

**Time Frame:** At baseline, 3 months, 6 months and 12 months, respectively

**Description:** To measure the severity of motor complications. Minimum value: 0, maximum value: 24, higher score means worse outcome.

**Measure:** Movement Disorders Society -Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part IV

**Time Frame:** At baseline, 3 months, 6 months and 12 months, respectively

**Description:** To evaluate involuntary movements. Minimum value: 0, maximum value: 104, higher score means worse outcome.

**Measure:** Unified Dyskinesia Rating Scale (UDyRS)

**Time Frame:** At baseline, 3 months, 6 months and 12 months, respectively

### Eligibility Module

**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).

**Maximum Age:** 80 Years

**Minimum Age:** 18 Years

**Sampling Method:** NON_PROBABILITY_SAMPLE

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

**Study Population:** We will enroll patients with Parkinson's disease, who are eligible for intestinal treatment with Lecigon® as a regular treatment option outside of the study protocol and under the accepted eligibility and indication criteria.

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** daniel.weiss@uni-tuebingen.de

**Name:** Daniel T Weiss, MD

**Phone:** 0049-7071-29-82340

**Role:** CONTACT

**Contact 2:**

**Email:** idil.cebi@med.uni-tuebingen.de

**Name:** Idil Cebi, MD

**Phone:** 0049-7071-29-85650

**Role:** CONTACT

#### Overall Officials

**Official 1:**

**Affiliation:** University Hospital Tuebingen

**Name:** Daniel Weiss, MD

**Role:** PRINCIPAL_INVESTIGATOR

### IPD Sharing Statement Module

**Description:** A study database will be established with our Institute for Clinical Epidemiology and Applied Biometry. Pseudonymized data can be made available after publication upon reasonable request to the Principal Investigator

**IPD Sharing:** UNDECIDED

### References Module

#### References

**Citation:** Weiss D, Volkmann J, Fasano A, Kuhn A, Krack P, Deuschl G. Changing Gears - DBS For Dopaminergic Desensitization in Parkinson's Disease? Ann Neurol. 2021 Nov;90(5):699-710. doi: 10.1002/ana.26164. Epub 2021 Jul 20.

**PMID:** 34235776

**Citation:** Weiss D, Ebersbach G, Moller JC, Schwarz J, Arlt C, Fritz B, Sensken SC, Eggert K. Do we start too late? Insights from the real-world non-interventional BALANCE study on the present use of levodopa/carbidopa intestinal gel in advanced Parkinson's disease in Germany and Switzerland. Parkinsonism Relat Disord. 2022 Oct;103:85-91. doi: 10.1016/j.parkreldis.2022.08.018. Epub 2022 Aug 24.

**PMID:** 36087571

**Citation:** Schmitt E, Krack P, Castrioto A, Klinger H, Bichon A, Lhommee E, Pelissier P, Fraix V, Thobois S, Moro E, Martinez-Martin P. The Neuropsychiatric Fluctuations Scale for Parkinson's Disease: A Pilot Study. Mov Disord Clin Pract. 2018 Mar 23;5(3):265-272. doi: 10.1002/mdc3.12607. eCollection 2018 May-Jun.

**PMID:** 30363450

**Citation:** Papay K, Mamikonyan E, Siderowf AD, Duda JE, Lyons KE, Pahwa R, Driver-Dunckley ED, Adler CH, Weintraub D. Patient versus informant reporting of ICD symptoms in Parkinson's disease using the QUIP: validity and variability. Parkinsonism Relat Disord. 2011 Mar;17(3):153-5. doi: 10.1016/j.parkreldis.2010.11.015. Epub 2010 Dec 24.

**PMID:** 21186135

**Citation:** Probst CC, Winter LM, Moller B, Weber H, Weintraub D, Witt K, Deuschl G, Katzenschlager R, van Eimeren T. Validation of the questionnaire for impulsive-compulsive disorders in Parkinson's disease (QUIP) and the QUIP-rating scale in a German speaking sample. J Neurol. 2014 May;261(5):936-42. doi: 10.1007/s00415-014-7299-6. Epub 2014 Mar 9. Erratum In: J Neurol. 2015 Sep;262(9):2200.

**PMID:** 24609972

**Citation:** Weintraub D, Mamikonyan E, Papay K, Shea JA, Xie SX, Siderowf A. Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease-Rating Scale. Mov Disord. 2012 Feb;27(2):242-7. doi: 10.1002/mds.24023. Epub 2011 Dec 1.

**PMID:** 22134954

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000020734

- Term: Parkinsonian Disorders

- ID: D000001480

- Term: Basal Ganglia Diseases

- ID: D000001927

- Term: Brain Diseases

- ID: D000002493

- Term: Central Nervous System Diseases

- ID: D000009422

- Term: Nervous System Diseases

- ID: D000009069

- Term: Movement Disorders

- ID: D000080874

- Term: Synucleinopathies

- ID: D000019636

- Term: Neurodegenerative Diseases

### Condition Browse Module - Browse Branches

- Abbrev: BC10

- Name: Nervous System Diseases

- Abbrev: All

- Name: All Conditions

- Abbrev: BC04

- Name: Neoplasms

- Abbrev: BC17

- Name: Skin and Connective Tissue Diseases

- Abbrev: BC18

- Name: Nutritional and Metabolic Diseases

### Condition Browse Module - Browse Leaves

- ID: M13213

- Name: Parkinson Disease

- Relevance: HIGH

- As Found: Parkinson's Disease

- ID: M22494

- Name: Parkinsonian Disorders

- Relevance: LOW

- As Found: Unknown

- ID: M25603

- Name: Ganglion Cysts

- Relevance: LOW

- As Found: Unknown

- ID: M16358

- Name: Synovial Cyst

- Relevance: LOW

- As Found: Unknown

- ID: M4774

- Name: Basal Ganglia Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M5204

- Name: Brain Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M5742

- Name: Central Nervous System Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M12029

- Name: Movement Disorders

- Relevance: LOW

- As Found: Unknown

- ID: M2217

- Name: Synucleinopathies

- Relevance: LOW

- As Found: Unknown

- ID: M21558

- Name: Neurodegenerative Diseases

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000010300

- Term: Parkinson Disease

### Intervention Browse Module - Browse Branches

- Abbrev: CaAg

- Name: Cardiotonic Agents

- Abbrev: All

- Name: All Drugs and Chemicals

- Abbrev: AnDyAg

- Name: Anti-Dyskinesia Agents

### Intervention Browse Module - Browse Leaves

- ID: M7473

- Name: Dopamine

- Relevance: LOW

- As Found: Unknown

- ID: M10982

- Name: Levodopa

- Relevance: LOW

- As Found: Unknown

- ID: M252093

- Name: Entacapone

- Relevance: LOW

- As Found: Unknown

- ID: M20595

- Name: Dopamine Agonists

- Relevance: LOW

- As Found: Unknown

- ID: M7471

- Name: Dihydroxyphenylalanine

- Relevance: LOW

- As Found: Unknown

### Misc Info Module

- Version Holder: 2024-05-24
