NCT03970239 - Serotonin in Impulse Control Disorders in Parkinson's Disease | Crick

Eligibility

Sex: ALLMin age: 30 YearsMax age: 80 YearsHealthy volunteers:

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

Difference in binding potential of [18 Fluorine]-altanserin ([18F]-altanserin) and [11 Carbon]-3-amino-4-(2-dimethylaminomethylphenylsulfanyl)-benzonitrile ([11C]-DASB) ([11C]-DASB)

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)

Time frame: 2-3 days

Secondary Outcomes

Ardouin Scale of Behavior in Parkinson's Disease (ASBPD)

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.

Time frame: 2-3 days

Questionnaire For Impulsive-Compulsive Disorders In Parkinson's Disease-Rating Scale (QUIP-RS)

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.

Time frame: 2-3 days

Urgency, Premeditation (lack of), Perseverance (lack of), Sensation Seeking Impulsive Behavior Scale (UPPS Impulsive Behavior Scale)

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

Time frame: 2-3 days

Movement Disorder Society (MDS) Unified Parkinson's Disease Rating Scale (MDS-UPDRS)

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.

Time frame: 2-3 days

Beck Depression Inventory II (BDI-II)

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.

Time frame: 2-3 days

Starkstein Apathy Scale (SAS)

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.

Time frame: 2-3 days

State-Trait Anxiety Inventory -Y (STAI-Y)

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.

Time frame: 2-3 days

Snaith-Hamilton Pleasure Scale (SHAPS)

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.

Time frame: 2-3 days

Temporal Experience of Pleasure Scale (TEPS)

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.

Time frame: 2-3 days

Stop Signal Reaction Time (SSRT)

Stop Signal Task

Time frame: 2-3 days

Discounting rate

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.

Time frame: 2-3 days

Proportion of premature responses

4 Choice Serial Reaction Time Task

Time frame: 2-3 days

Polymorphism rs6313 (or T102C) of the serotonin 5-Hydroxytryptamine 2A (5-HT2A) receptor

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.

Time frame: 2-3 days

Polymorphism 5-HydroxyTryptamine (serotonin) Transporter Gene-Linked Polymorphic Region (5-HTTLPR)/rs25531 of the serotonin transporter (SERT)

Time frame: 2-3 days

Magnetic Resonance Imaging metrics: anatomical imaging

Anatomical imaging using a T1-weighted Magnetization-Prepared RApid Gradient-Echo (T1\_MPRAGE) sequence for morphometry.

Time frame: 2-3 days

Magnetic Resonance Imaging metrics: Diffusion Weighted imaging

Diffusion weighted imaging for Diffusion Tensor Imaging (DTI) and tractography

Time frame: 2-3 days

Magnetic Resonance Imaging metrics: Resting State Functional Imaging

Resting State Functional Imaging for functional connectivity

Time frame: 2-3 days

Serotonin in Impulse Control Disorders in Parkinson's Disease

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts