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Evaluation of the Nonmotor Symptomatology of Parkinsonian Patients Treated With Two Strategies Related to Apomorphine Pump Therapy in French Hospitals (AGAPO)

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ClinicalTrials.gov Identifier: NCT03693872
Recruitment Status : Recruiting
First Posted : October 3, 2018
Last Update Posted : May 29, 2019
Sponsor:
Information provided by (Responsible Party):
Rennes University Hospital

Brief Summary:
There is currently no consensus on the adequate concomitant treatment to apomorphine pump in Parkinson's disease (PD). In practice, some centers withdraw all dopaminergic agonists when initiating apomorphine pump therapy, whereas others combine the two. To date, there has been no study led to determine the best strategy for efficiently treating motor and nonmotor symptoms, as well as improving patients' quality of life (QoL). This preliminary study, entitled AGAPO, aims at identifying significant differences in patients' evolution (nonmotor symptoms and quality of life), over a course of 6 months, depending on the two strategies adopted in French centers (apomorphine pump with or without dopaminergic agonists), through the Non Motor Symptoms Scale (NMSS, Chaudhuri et al, 2017).

Condition or disease Intervention/treatment Phase
Parkinson Disease Drug: Apomorphine Drug: Dopaminergic Agonist + Apomorphine Not Applicable

Detailed Description:

The recruitment period will be 24 months. The duration of the study will be 6 months for each patient due to adjustments of apomorphine pump parameters and oral medication as well time needed for motor and nonmotor changes to develop and influence QoL.

This study will be done without any modification of the planned treatment plan for each patient included. The treatments are administered in accordance with their marketing authorization and according to the usual practices of each center. No additional visits are expected.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 42 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Interventional to minimal risks and constraints, non randomized, open
Masking: Single (Participant)
Masking Description: open
Primary Purpose: Other
Official Title: Evaluation of the Nonmotor Symptomatology of Parkinsonian Patients Treated With Two Strategies Related to Apomorphine Pump Therapy in French Hospitals
Actual Study Start Date : May 15, 2019
Estimated Primary Completion Date : November 15, 2021
Estimated Study Completion Date : March 15, 2022


Arm Intervention/treatment
Apomorphine
Withdrawal of dopaminergic agonists at pump initiation
Drug: Apomorphine
Apomorphine (5 mg/ml), supplied as solution for infusion in a 10 ml glass ampoule Hourly flow rate adjusted during the whole duration of the study to obtain the best effect in each patient
Other Name: APO

Dopaminergic Agonist + Apomorphine
Continuation of dopaminergic agonists at pump initiation
Drug: Dopaminergic Agonist + Apomorphine
Apomorphine (5 mg/ml), supplied as solution for infusion in a 10 ml glass ampoule Hourly flow rate adjusted during the whole duration of the study to obtain the best effect in each patient and associated with dopaminergic agonists
Other Name: AGAPO




Primary Outcome Measures :
  1. Difference in the Non Motor Symptoms Scale (NMSS) between the Baseline assessment and the assessment at 6 months' follow up [ Time Frame: 6 months ]
    The Non-Motor Symptoms Scale (NMSS) measures the frequency and severity of a range of non-motor symptoms in Parkinson's Disease, through 30 questions grouped into 9 domains: cardiovascular, sleep/fatigue, mood/cognition, perceptual problems/hallucinations, attention/memory, gastro-intestinal tract, urinary, sexual function, and miscellaneous (pain, taste/smell, weight change, excessive sweating). Severity is rated on a scale from 0 (none) to 3 (severe). Frequency is rated on a scale from 1 (rarely) to 4 (very frequent). Item scores are calculated as the product of severity and frequency; the total score is obtained by summing the item scores. The NMSS total score ranges from 0 to 360 with a lower score indicating fewer symptoms. A negative change from baseline indicates improvement in symptoms (reduced score).


Secondary Outcome Measures :
  1. Change in the Parkinson's Disease Quality of Life Questionnaire (PDQ39) between the Baseline assessment and the assessment at 6 months' follow up [ Time Frame: 6 months ]
    Parkinson's Disease Quality of Life Questionnaire (PDQ-39): the 39-Item Parkinson's Disease Questionnaire (PDQ-39) is a commonly used measure of self-appraisal in PD. It is a measure of health status and quality of life, by assessing difficulties in 8 dimensions of daily living: mobility (10 items), activities of daily living (6 items), emotional well-being (6 items), stigma (4 items), social support (3 items), cognition (4 items), communication (3 items) and bodily discomfort (3 items). The frequency of each event is determined by selecting one of 5 options: never (scored 0) / occasionally (scored 1) / sometimes (2) / often (3) / always (4). Each dimension total score range from 0 to 100, with lower scores reflecting better quality of life.

  2. Change in the Neurologist Global Impression of change (CGI) between the Baseline assessment and the assessment at 6 months' follow up [ Time Frame: 6 months ]
    The Change in the Neurologist (clinician) Global Impression of change (CGI) provides a brief, stand-alone assessment of the clinician's view of the patient's global functioning prior to and after initiating a study medication. It ranges from severely impaired to dramatically improved.

  3. Change in non-motor aspects of experiences of daily living (MDS-UPDRS I) between the Baseline assessment and the assessment at 6 months' follow up [ Time Frame: 6 months ]
    The Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) is the standard validated tool for the assessment of patients with Parkinson's Disease (PD). This combined scale includes subsections collecting data regarding: nonmotor experiences of daily living (part I), their motor experiences of daily living (part II) an examination of the motor features of PD (part III), and motor complications arising from the use of dopamine replacement (part IV). The Part I include 13 items (6 semistructured interview items and 7 self‐reported items) scored on a scale from 0 (normal) to 4 (severe). Higher scores reflect worse condition.

  4. Change in apathy assessed on the long version of Lille Apathy Rating Scale between the Baseline assessment and the assessment at 6 months' follow up (LARS) [ Time Frame: 6 months ]
    The Lille apathy rating scale (LARS) is a measure of apathy through nine domains (each corresponding to a clinical manifestation of apathy: everyday productivity, interests, taking the initiative, novelty seeking, motivation - Voluntary actions, emotional responses, concern, social life & self-awareness) and 33 queries. The interview is structured, with a precise scoring mode for each reply (-2 to 2); when an item does not apply to the patient or the reply cannot be classified, it is scored "0" (for non-applicable and/or non-classifiable) The scale's overall score ranges from -36 to +36, with highest scores reflecting apathy severity. 4 factorial sub-scores (intellectual curiosity, emotion, action initiation and self-awareness) are calculated from sub-scale scores.

  5. Change in occurrence of anxiety (STAI-YA) between the Baseline assessment and the assessment at 6 months' follow up [ Time Frame: 6 months ]
    Present feelings

  6. Change in occurrence of anxiety (STAI-YB) between the Baseline assessment and the assessment at 6 months' follow up [ Time Frame: 6 months ]
    General feelings

  7. Change in behavioral symptoms assessed by Ardouin Scale between the Baseline assessment and the assessment at 6 months' follow up [ Time Frame: 6 months ]
    Changes from baseline in hyper and hypo dopaminergic symptoms scores will be assessed through the Ardouin Scale of Behavior in Parkinson's Disease (ASBPD). It is designed for assessing mood and behavior with a view to quantifying changes related to Parkinson's disease, to dopaminergic medication, and to non‐motor fluctuations. Its 21 items address nonmotor symptoms and are grouped into four dimensions: general psychological assessment, apathy, nonmotor fluctuations and hyperdopaminergic behaviors, with a 5-point rating scale ranging from 0 (Absent) to 4 (Severe). A score ≥ 2 is considered as a warning sign.

  8. Change in emotional function assessed by the short form of the TEIQue between the Baseline assessment and the assessment at 6 months' follow upscale [ Time Frame: 6 months ]
    The Trait Emotional Intelligence Questionnaire-Short Form (TEIQue-SF) aims at evaluating emotional intelligence through a self-report inventory that measure global trait emotional intelligence (trait EI) through a 30-item questionnaire. The trait EI is about perceptions and not about abilities, competencies or skills ; high scores are not necessarily adaptive (good) and low scores are not necessarily maladaptive (bad).

  9. Change in emotional function assessed by the short form of the BEQ scale between the Baseline assessment and the assessment at 6 months' follow up [ Time Frame: 6 months ]
    The Berkeley Expressivity Questionnaire (BEQ) is a self-report measure of three emotional expressivity facets related to emotional expressivity: expressivity of negative and positive emotions, and strength of expression impulse. Each of the 16 items is answered on a 7-point Likert-type ranging from 1 (strongly disagree) to 7 (strongly agree). The 3 facets can be kept as separate scores or combined to form an overall Emotional Expressivity score.

  10. Change in motor aspects of experiences of daily in "on" and "off" medication (MDS-UPDRS II) between the Baseline assessment and the assessment at 6 months' follow up [ Time Frame: 6 months ]
    The Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) is the standard validated tool for the assessment of patients with Parkinson's Disease (PD). This combined scale includes subsections collecting data regarding: nonmotor experiences of daily living (part I), their motor experiences of daily living (part II) an examination of the motor features of PD (part III), and motor complications arising from the use of dopamine replacement (part IV). The Part II include 13 self‐reported items) scored on a scale from 0 (normal) to 4 (severe). Higher scores reflect worse condition.

  11. Change in motor examination during "on" periods (MDS-UPDRS III) between the Baseline assessment and the assessment at 6 months' follow up [ Time Frame: 6 months ]
    The Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) is the standard validated tool for the assessment of patients with Parkinson's Disease (PD). This combined scale includes subsections collecting data regarding: nonmotor experiences of daily living (part I), their motor experiences of daily living (part II) an examination of the motor features of PD (part III), and motor complications arising from the use of dopamine replacement (part IV). The Part III include 18 items scored on a scale from 0 (normal) to 4 (severe). Higher scores reflect worse condition.

  12. Change in motor complications with MDS-UPDRS IV between the Baseline assessment and the assessment at 6 months' follow up [ Time Frame: 6 months ]
    The Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) is the standard validated tool for the assessment of patients with Parkinson's Disease (PD). This combined scale includes subsections collecting data regarding: nonmotor experiences of daily living (part I), their motor experiences of daily living (part II) an examination of the motor features of PD (part III), and motor complications arising from the use of dopamine replacement (part IV). The Part IV include 6 items assessed in a semistructured interview, scored on a scale from 0 (normal) to 4 (severe). Higher scores reflect worse condition.

  13. Change in motor examination with the Schwab and England scale between the Baseline assessment and the assessment at 6 months' follow up [ Time Frame: 6 months ]

    The Schwab & England activities of daily living evaluates patients' autonomy through a percentage ranging from 0% (=Vegetative functions such as swallowing, bladder and bowel functions are not functioning. Bedridden.) to 100% ( = Completely independent. Able to do all chores without slowness, difficulty or impairment. Essentially normal).

    Unaware of any difficulty.


  14. Change in motor examination with the Hoehn & Yarr scale [ Time Frame: 6 months ]
    The severity of PD is assessed through the Modified Hoehn & Yahr rating scale, consisting of 10levels comprised between 0 (best), 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5 (worst).

  15. Change in cognitive function assessed by the MoCA scale between the Baseline assessment and the assessment at 6 months' follow up [ Time Frame: 6 months ]
    The Montreal Cognitive Assessment (MoCA) is a short tool (one-page 30-point test administered in approximately 10 minutes) to evaluate a multitude of cognitive domains (visuospatial / executive functioning, object naming, memory, attention, language, abstraction, orientation). MoCA scores range between 0 and 30; a score ≥ 26 is considered to be normal.

  16. Change of dose for treatments assessed by levodopa (L-DOPA) équivalents between the Baseline assessment and the assessment at 6 months' follow up [ Time Frame: 6 months ]
  17. Frequency, type and severity of therapy-related adverse events [ Time Frame: 6 months ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Adults aged = or > 18 years,
  • Idiopathic PD (According to British Brain Bank Criteria) without any other known or suspected cause of symptoms,
  • Indicated for apomorphine pump therapy and according to the centers' practice, treatment with apomorphine pump association with dopamine agonists or apomorphine pump therapy alone
  • Presence of fluctuations for > 3 years,
  • Patients covered with social insurance.
  • Written informed consent

Exclusion Criteria:

  • Neurological (other than Parkinson's disease) or severe psychiatric history (depression, schizophrenia, addiction, bipolar disorder, anxiety and depressive disorders);
  • Severe neurocognitive disorders (DSM-V)
  • History of use of apomorphine pump treatment or deep brain stimulation or lesional surgery for PD or intrajejunal L-Dopa;
  • History or current drug or alcohol abuse or dependencies;
  • History of impulse control disorders;
  • Adults legally protected (under judicial protection, guardianship or supervision), persons deprived of their liberty;
  • Inability to understand the information given on the study, to express informed consent.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03693872


Contacts
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Contact: Marc VERIN, PH 299289842 ext +33 marc.verin@chu-rennes.fr
Contact: Manon Auffret

Locations
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France
CHU La Timone Not yet recruiting
Marseille, France
Contact: Alexandre EUSEBIO, PH         
Contact       alexandre.eusebio@ap-hm.fr   
Hôpital Gui de Chauliac Active, not recruiting
Montpellier, France, 34295
CH Caremeau Active, not recruiting
Nîmes, France, 30029
CHU La Pitié Salpêtrière Active, not recruiting
Paris, France, 75013
CHU de Reims- hôpital Maison Blanche Recruiting
Reims, France, 51100
Contact: Anne DOE DE MAINDREVILLE, MD         
Contact       adoedemaindreville@chu-reims.fr   
CHU de Rennes Active, not recruiting
Rennes, France, 35033
CHU Charles Nicolle Active, not recruiting
Rouen, France, 76000
Sponsors and Collaborators
Rennes University Hospital
Investigators
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Principal Investigator: Marc VERIN, PH Rennes University Hospital

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Responsible Party: Rennes University Hospital
ClinicalTrials.gov Identifier: NCT03693872     History of Changes
Other Study ID Numbers: 35RC18_9721_AGAPO
First Posted: October 3, 2018    Key Record Dates
Last Update Posted: May 29, 2019
Last Verified: May 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Rennes University Hospital:
Parkinson
Nonmotor symptomatology

Additional relevant MeSH terms:
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Parkinson Disease
Parkinsonian Disorders
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Movement Disorders
Neurodegenerative Diseases
Dopamine
Apomorphine
Dopamine Agonists
Cardiotonic Agents
Sympathomimetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Dopamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Protective Agents
Emetics
Gastrointestinal Agents