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Serotonin in Impulse Control Disorders in Parkinson's Disease (Park-IMPULSE)

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ClinicalTrials.gov Identifier: NCT03970239
Recruitment Status : Recruiting
First Posted : May 31, 2019
Last Update Posted : April 8, 2020
Sponsor:
Information provided by (Responsible Party):
Hospices Civils de Lyon

Brief Summary:

Impulse control disorders are frequent and troublesome in patients with Parkinson's disease. However, the cerebral functional alterations related to impulse control disorders in Parkinson's disease are poorly understood and may involve the serotoninergic system besides alterations in the dopaminergic system.

The primary objective of this study is to investigate the cerebral functional alterations in the serotoninergic system in patients with Parkinson's disease and impulse control disorders using Positron Emission Tomography with highly specific radiotracers of serotonin transporter (SERT) using [11 Carbon]-3-amino-4-(2-dimethylaminomethylphenylsulfanyl)-benzonitrile ([11C]-DASB) and of serotonin 5-Hydroxytryptamine 2A (5-HT2A) receptor using [18 Fluorine]-altanserin ([18F]-altanserin), in comparison to patients with Parkinson's disease without impulse control disorders and healthy volunteers.


Condition or disease Intervention/treatment Phase
Parkinson Disease Impulse Control Disorders Drug: Positron Emission Tomography using [11 Carbon]-3-amino-4-(2-dimethylaminomethylphenylsulfanyl)-benzonitrile ([11C]-DASB) and [18 Fluorine]-altanserin ([18F]-altanserin) Drug: Positron Emission Tomography using [18 Fluorine]-altanserin ([18F]-altanserin) Not Applicable

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 45 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: Role of the Serotoninergic System in Impulse Control Disorders in Parkinson's Disease
Actual Study Start Date : May 13, 2019
Estimated Primary Completion Date : February 13, 2022
Estimated Study Completion Date : February 13, 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Parkinson's Disease patients

All study participants undergo functional imaging of the serotoninergic system with Positron Emission Tomography (PET) using [11 Carbon]-3-amino-4-(2-dimethylaminomethylphenylsulfanyl)-benzonitrile ([11C]-DASB) and [18 Fluorine]-altanserin ([18F]-altanserin). [11C] -DASB is a highly specific PET radiotracer which binds to the serotonin transporter (SERT).

[18F]-altanserin is a highly specific PET radiotracer which specifically binds to the serotonin 5-hydroxytryptamine receptor 2A (5-HT2A) receptor.

Drug: Positron Emission Tomography using [11 Carbon]-3-amino-4-(2-dimethylaminomethylphenylsulfanyl)-benzonitrile ([11C]-DASB) and [18 Fluorine]-altanserin ([18F]-altanserin)

Imaging of the serotoninergic system with Positron Emission Tomography using [11 Carbon]-3-amino-4-(2-dimethylaminomethylphenylsulfanyl)-benzonitrile ([11C]-DASB) and [18 Fluorine]-altanserin ([18F]-altanserin). During this study, subjects will receive a single intravenous administration of approximately 4 Megabecquerel/kilogram (MBq/kg) of [11C]-DASB immediately prior to imaging using Positron Emission Tomography (PET). The effective dose in human body is about 2.1 milliSievert (mSv).

On a separate day, subjects will receive a single intravenous administration of approximately 3.7 MBq/kg of [18F]-altanserin for 120 minutes prior to imaging using Positron Emission Tomography (PET). The effective dose in human body is about 8.4 mSv.


Experimental: Imaging of healthy volunteers

All healthy volunteers undergo functional imaging of the serotoninergic system with Positron Emission Tomography (PET) using [18F]-altanserin.

[18F]-altanserin is a highly specific PET radiotracer which specifically binds to the serotonin 5-hydroxytryptamine receptor 2A (5-HT2A) receptor.

Drug: Positron Emission Tomography using [18 Fluorine]-altanserin ([18F]-altanserin)
Imaging of the serotoninergic system with Positron Emission Tomography using [18 Fluorine]-altanserin ([18F]-altanserin). During this study, subjects will receive a single intravenous administration of approximately 3.7 Megabecquerel/kilogram (MBq/kg) of [18F]-altanserin 120 minutes prior to imaging using Positron Emission Tomography. The effective dose in human body is about 8.4 mSv.




Primary Outcome Measures :
  1. Difference in binding potential of [18 Fluorine]-altanserin ([18F]-altanserin) and [11 Carbon]-3-amino-4-(2-dimethylaminomethylphenylsulfanyl)-benzonitrile ([11C]-DASB) ([11C]-DASB) [ Time Frame: 2-3 days ]
    Between-group difference of binding potential of [18 Fluorine]-altanserin ([18F]-altanserin) and [11 Carbon]-3-amino-4-(2-dimethylaminomethylphenylsulfanyl)-benzonitrile ([11C]-DASB) ([11C]-DASB)


Secondary Outcome Measures :
  1. Ardouin Scale of Behavior in Parkinson's Disease (ASBPD) [ Time Frame: 2-3 days ]
    The Ardouin Scale of Behavior in Parkinson's Disease (ASBPD) evaluates hypo- and hyperdopaminergic behaviors and can also detect and quantify neuropsychiatric fluctuations by evaluating OFF-drug dysphoria and ON-drug euphoria. It is based on a semi-structured interview that encompasses the whole spectrum of behavioral spectrum from hypo-to hyperdopaminergic syndromes as well as non-motor fluctuations. The scale consists of 18 items addressing non-motor symptoms, grouped in four parts: general psychological evaluation, apathy, non-motor fluctuations and hyperdopaminergic behaviors. The rating in five points (0-4 from absent to severe) is carried out during a semi-structured interview. Open-ended questions introduce each item, allowing patients to express themselves as freely as possible. Close-ended questions permit the rating of severity and intensity.

  2. Questionnaire For Impulsive-Compulsive Disorders In Parkinson's Disease-Rating Scale (QUIP-RS) [ Time Frame: 2-3 days ]
    The Questionnaire For Impulsive-Compulsive Disorders In Parkinson's Disease-Rating Scale (QUIP-RS) is designed to measure severity of symptoms and support a diagnosis of impulse control disorders and related disorders in Parkinson's Disease (PD). The QUIP-RS is administered with an instruction sheet that provides examples of the behaviors being assessed and a brief description of the categories for frequency (never [0] = not at all, rarely [1] = infrequently or 1 day/week, etc.). Scores for each Impulsive Compulsive Disorder (ICD) and related disorder range from 0 to 16, with a higher score indicating greater severity (frequency) of symptoms. The total QUIP-RS score for all ICDs and related disorders combined ranges from 0 to 112.

  3. Urgency, Premeditation (lack of), Perseverance (lack of), Sensation Seeking Impulsive Behavior Scale (UPPS Impulsive Behavior Scale) [ Time Frame: 2-3 days ]

    The full version of the UPPS-P Scale is composed of 59 items, with 10-14 items per scale. Items are scored on a 4-point scale:

    Agree Strongly = 1 Agree Some = 2 Disagree Some = 3 Disagree Strongly = 4

    Higher values translate into higher levels of impulsivity. The results allow assessement of the patient according to five impulsive personality traits:

    • Negative urgency: tendency to act rashly under extreme negative emotions
    • Lack of Premeditation: tendency to act without thinking
    • Lack of Perseverance: inability to remain focused on a task
    • Sensation Seeking: tendency to seek out novel and thrilling experiences
    • Positive Urgency: tendency to act rashly under extreme positive emotions

  4. Movement Disorder Society (MDS) Unified Parkinson's Disease Rating Scale (MDS-UPDRS) [ Time Frame: 2-3 days ]
    The MDS-UPDRS is composed of four parts, namely, I: Non-motor Experiences of Daily Living; II: Motor Experiences of Daily Living; III: Motor Examination; IV: Motor Complications and includes 65 items. Each question has five responses that are linked to commonly accepted clinical terms: 0 = normal, 1 = slight, 2 = mild, 3 = moderate, and 4 = severe. The overall progression of disability is given a score ranging from 0 = no disability 1= slight disability 2= moderate disability 3= high disability and 4= severe disability.

  5. Beck Depression Inventory II (BDI-II) [ Time Frame: 2-3 days ]

    The Beck Depression Inventory (BDI-II) is used to measure the severity of depression. It contains 21 questions, each answer being scored on a scale value of 0 to 3. Higher total scores indicate more severe depressive symptoms:

    • 0-13: minimal depression
    • 14-19: mild depression
    • 20-28: moderate depression
    • 29-63: severe depression.

  6. Starkstein Apathy Scale (SAS) [ Time Frame: 2-3 days ]
    For this scale, patients are asked to answer 14 questions, each of which is scored on a 4-point scale of 0-3, and apathy is rated as more severe as the total score (0-42) increases.

  7. State-Trait Anxiety Inventory -Y (STAI-Y) [ Time Frame: 2-3 days ]
    The State-Trait Anxiety Inventory measures anxiety by assessing someone's state (S) and trait (T) anxiety at the same time. Its combined format consists of 40 questions. The S-Anxiety scale (STAI Form Y-1) consists of twenty statements that evaluate how the respondent feels "right now, at this moment". The T- Anxiety scale (STAI Form Y-2) consists of twenty statements that evaluate how the respondent feels "generally". In responding to the S-Anxiety scale, the subjects choose the number that best describes the intensity of their feelings: (1) not at all, (2) somewhat, (3) moderately, (4) very much so. In responding to the T-Anxiety scale, subjects rate the frequency of their feelings on the following four-point scale: (1) almost never, (2) sometimes, (3) often, (4) almost always. Each STAI item is given a weighted score of 1 to 4. Scores for both the S-Anxiety and the T-Anxiety scales can vary from a minimum of 20 to a maximum of 80 with higher scores correlating to higher anxiety.

  8. Snaith-Hamilton Pleasure Scale (SHAPS) [ Time Frame: 2-3 days ]
    The SHAPS measures the subject's ability to experience pleasure (hedonic tone) and its absence (anhedonia). It consists of 14 items with 4 possible responses: Definitely Agree, Agree, Disagree, Definitely Disagree. A score from 0- 14 is possible (1 point for each response in the Disagree category and 0 points for each response in the Agree category). The higher the score the less the subject is able to experience pleasure.

  9. Temporal Experience of Pleasure Scale (TEPS) [ Time Frame: 2-3 days ]
    Measure specifically designed to capture the anticipatory and consummatory facets of pleasure. It consists of 10 questions assessing anticipatory pleasure (TEPS-ANT) and 8 questions assessing consummatory pleasure (TEPS-CON) using a 6-point fixed choice response format ranging from 1 = very false for me to 6 = very true for me. The higher the score for each section, the more the subject experiences anticipatory pleasure and consummatory pleasure, respectively.

  10. Stop Signal Reaction Time (SSRT) [ Time Frame: 2-3 days ]
    Stop Signal Task

  11. Discounting rate [ Time Frame: 2-3 days ]
    27-item Monetary Choice Questionnaire: for each question, patients will choose between two different monetary values (a high monitary value versus a low monitary value) in order to determine the patient's level of impulsiveness.

  12. Proportion of premature responses [ Time Frame: 2-3 days ]
    4 Choice Serial Reaction Time Task

  13. Polymorphism rs6313 (or T102C) of the serotonin 5-Hydroxytryptamine 2A (5-HT2A) receptor [ Time Frame: 2-3 days ]
    Polymorphism rs6313 also called T102C or C102T is a gene variation, a single nucleotide polymorphism (SNP) in the human Hydroxytryptamine Receptor 2A (HTR2A) gene that codes for the 5-HT2A receptor. The SNP is a synonymous substitution located in exon 1 of the gene where it is involved in coding the 34th amino acid as serine.

  14. Polymorphism 5-HydroxyTryptamine (serotonin) Transporter Gene-Linked Polymorphic Region (5-HTTLPR)/rs25531 of the serotonin transporter (SERT) [ Time Frame: 2-3 days ]
    Polymorphism 5-HydroxyTryptamine (serotonin) Transporter Gene-Linked Polymorphic Region (5-HTTLPR)/rs25531 of the serotonin transporter (SERT)

  15. Magnetic Resonance Imaging metrics: anatomical imaging [ Time Frame: 2-3 days ]
    Anatomical imaging using a T1-weighted Magnetization-Prepared RApid Gradient-Echo (T1_MPRAGE) sequence for morphometry.

  16. Magnetic Resonance Imaging metrics: Diffusion Weighted imaging [ Time Frame: 2-3 days ]
    Diffusion weighted imaging for Diffusion Tensor Imaging (DTI) and tractography

  17. Magnetic Resonance Imaging metrics: Resting State Functional Imaging [ Time Frame: 2-3 days ]
    Resting State Functional Imaging for functional connectivity



Information from the National Library of Medicine

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Ages Eligible for Study:   30 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

Group 1 Patients with Parkinson's disease and impulse control disorders

  • Patients with a diagnosis of clinically established or clinically probable Parkinson's disease according to the Movement Disorder Society (MDS) Clinical Diagnostic Criteria for Parkinson's Disease
  • Patients aged ≥ 30 and ≤ 80 years old
  • Patients presenting currently with impulse control disorders or having presented with impulse control disorders in the last 2 years (Ardouin Behavior Scale score ≥2 for one or more of the following items: eating behavior; compulsive buying; pathological gambling; hypersexuality) , following the diagnosis of Parkinson's disease
  • Patients able to sign the consent document and willing to participate in all aspects of the study

Patients with Parkinson's disease and without impulse control disorders

  • Patients with a diagnosis of clinically established or clinically probable Parkinson's disease according to the MDS Clinical Diagnostic Criteria for Parkinson's Disease
  • Patients aged ≥ 30 and ≤ 80 years old
  • Patients not currently presenting with impulse control disorders and other hyperdopaminergic behaviors and not having ever presented with impulse control disorders
  • Patients able to sign a consent document and willing to participate in all aspects of the study

Group 2 : Healthy volunteers

Subjects aged ≥ 30 and ≤ 80 years old

  • Subjects not currently presenting with impulse control disorders or hyperdopaminergic behaviors and not having ever presented with impulse control disorders
  • Subjects able to sign a consent document and willing to participate in all aspects of the study

Exclusion Criteria:

Group 1 :

Patients with Parkinson's disease and impulse control disorders

  • Patients with Montreal Cognitive Assessment score ≤24 or Frontal Assessment Battery score ≤14
  • Patients not able to perform Positron Emission Tomography (PET) or Magnetic Resonance Imaging (MRI)
  • Patients presenting with other severe medical condition or other parkinsonian syndrome
  • Patients treated with Deep Brain Stimulation or levodopa pump
  • Patients treated with drugs or consuming recreative drugs specifically interfering with the serotoninergic, noradrenergic or opiate systems in the last 3 months
  • Patients presenting with substance dependence, except for tobacco
  • Patients with Body Mass Index ≥ 35kilogram/meters2 (kg/m2)

Patients with Parkinson's disease and without impulse control disorders

  • Patients with Montreal Cognitive Assessment score ≤24 or Frontal Assessment Battery score ≤14
  • Patients not able to perform Positron Emission Tomography or Magnetic Resonance Imaging
  • Patients presenting with other severe medical condition or other parkinsonian syndrome
  • Patients treated with Deep Brain Stimulationor levodopa pump
  • Patients treated with drugs or consuming recreative drugs specifically interfering with the serotoninergic, noradrenergic or opiate systems in the last 3 months
  • Patients presenting with substance dependence, except for tobacco
  • Patients with Body Mass Index ≥35kg/m2

Group 2 : Healthy volunteers

  • Subjects with Montreal Cognitive Assessment score ≤24 or Frontal Assessment Battery score ≤14
  • Subjects not able to perform Positron Emission Tomography or Magnetic Resonance Imaging
  • Subjects presenting with neurologic, psychiatric or other severe medical condition
  • Subjects treated with drugs or consuming recreative drugs specifically interfering with the serotoninergic, noradrenergic or opiate systems in the last 3 months
  • Subjects presenting with substance dependence, except for tobacco
  • Subjects with Body Mass Index ≥35kg/m2

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): NCT03970239


Contacts
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Contact: Stéphane THOBOIS, PhD 4 72 35 72 18 ext 33 stephane.thobois@chu-lyon.fr

Locations
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France
Hospices Civils de Lyon Recruiting
Bron, France
Contact: THOBOIS STEPHANE         
Sponsors and Collaborators
Hospices Civils de Lyon
Investigators
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Principal Investigator: Stéphane THOBOIS, PhD Hospices Civils de Lyon
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Responsible Party: Hospices Civils de Lyon
ClinicalTrials.gov Identifier: NCT03970239    
Other Study ID Numbers: 69HCL18_0012
2019-000340-99 ( EudraCT Number )
First Posted: May 31, 2019    Key Record Dates
Last Update Posted: April 8, 2020
Last Verified: February 2020

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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 Hospices Civils de Lyon:
Parkinson's disease
Impulse control disorders
Serotoninergic system
Positron Emission Tomography (PET)
Additional relevant MeSH terms:
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Parkinson Disease
Disease
Disruptive, Impulse Control, and Conduct Disorders
Pathologic Processes
Parkinsonian Disorders
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Movement Disorders
Neurodegenerative Diseases
Mental Disorders
Ketanserin
Fluorides
Altanserin
Cariostatic Agents
Protective Agents
Physiological Effects of Drugs
Serotonin Antagonists
Serotonin Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Antihypertensive Agents
Platelet Aggregation Inhibitors