Hallucinations in Parkinson's Disease

Parkinson Disease Psychosis Clinical Trial

Official title:

Unravelling Dysfunctional Brain Networks in Patients With Parkinson's Disease Suffering From Hallucinations

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04592965
• Other study ID #: UH_PD
• Status: Recruiting
• Phase: N/A
• Start date: August 17, 2020
• Est. completion date: December 1, 2021

Study information

• Verified date: October 2020
• Source: Ecole Polytechnique Fédérale de Lausanne
• Contact: Olaf Blanke
• Phone: +41 21 693 9621
• Email: olaf.blanke[@]epfl.ch
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Investigation on how robotically mediated sensorimotor stimulation induces and triggers presence hallucinations in different clinical groups of parkinsonian patients, and in aged-matched controls

Description:

Parkinson's Disease (PD) is a condition mostly known and characterized by motor symptoms, such as tremors, rigidity, bradykinesia, amongst others. Yet, recent bodies of research have identified a significant number of non-motor symptoms that also accompany the unfolding of this disease. These non-motor symptoms mainly focus on hallucinations that will develop with the course of the disease, and will affect approximately 50% of the patients suffering from Parkinson's. This number rises to 70% if minor hallucinations, mild phenomena and poorly-structured hallucinations, are included. Despite the potential impact in the patients' lives, and previous efforts to study these phenomena, the brain changes that underly hallucinations in PD are still poorly understood. With the current study the investigators aim to improve this understanding, by studying the most common minor hallucination in Parkinson's Disease, the Presence Hallucination (PH), which can be defined as the strange sensation of perceiving someone behind when no one is actually there. To study it in a controlled manner, the investigators will induce this hallucination with an extensively verified paradigm, which gives rise to this sensation through robotically-mediated sensorimotor stimulation, in both healthy individuals, and PD patients. The researchers intend to discern the sensitivity of different groups of PD patients to the induction of this hallucination, by targeting PD patients, with hallucinations including PH, with hallucinations but without PH, without any hallucinations, and an aged match control group with no neurological comorbidities. The investigators intended to extend previous work on the induction of the PH in PD patients, by identifying the neural correlates of this induction in these patients, in a similar fashion to previous work in healthy individuals. Moreover, the researchers also intend to extend the general understanding of the basis for hallucinations in PD by extending what was done in previous work, to more stratified cohorts of PD patients, that will not only be analysed in terms of static during rest, but also in terms of dynamic connectivity, and will also perform the PH-inducing task in the scanner, as mentioned before.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: December 1, 2021
• Est. primary completion date: December 1, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Diagnosed with Parkinson's disease (expect for healthy controls)
• Able to understand instructions and provide informed consent.
• Native speaking language of experimental site (or acquisition of language of experimental site before 6 years old).
• Montreal Cognitive Assessment (Nasreddine & Patel, 2016) with score = 22.
• Able to manipulate the robotic device.

Exclusion Criteria:

• For PD patients only: Neurological comorbidities other than Parkinson's disease (e.g. Alzheimer's disease, vascular dementia, multiple sclerosis, stroke, traumatic brain injury, epilepsy, chronic migraine, etc.)
• For healthy controls only: Parkinson's disease or other neurological illnesses
• History or current condition of substance abuse and/or dependence (e.g., alcohol, drugs).
• Suffering from or diagnosed with psychiatric illnesses according to DSM-V criteria (e.g., schizophrenia, bipolar disorders, autism, personality disorders, phobia etc.).
• Family history (1st and 2nd degree) of psychiatric disorders (e.g., schizophrenia or bipolar disorders).
• Severe somatic illnesses (e.g., cancer).
• Severe tremors or physical disability preventing optimal use of robotic device.
• Participating in a pharmacological study.
• Local or general anaesthesia 30 days prior experiment
• Inability to provide informed consent (legal guardianship)
• For the MRI part only: body weight exceeding 160kg, implanted metallic devices, implant for deep brain stimulation, foreign metallic objects, unstable angina, cardio-vascular diseases, tattoos with metallic components, external metallic objects, claustrophobia, pregnancy.

Related Conditions & MeSH terms

• Hallucinations
• Parkinson Disease
• Parkinson Disease Psychosis

Intervention

Behavioral:
• Clinical and neuropsychological assessments
The assessment of disease state, clinical condition, and of cognitive and neuropsychological attributes.
• Induction of PH and associated bodily states
Assessment of subjective sensitivity to the induction of the PH and associated bodily states, for different populations of PD patients and healthy aged-matched controls

Other:
• Resting-state fMRI acquisition
Investigation of neural mechanisms at rest, that are potentially disrupted at different degrees, for the different clinical groups of PD patients, compared to the healthy aged-matched controls
• Induction of PH and associated bodily states (MRI)
Assessment of subjective sensitivity to the induction of the PH and associated bodily states, for different populations of PD patients and healthy aged-matched controls Assessment and comparison of the neural mechanisms responsible for the induction of the PH and associated bodily illusions, in different groups of PD patients and healthy aged-matched controls

Locations

Country	Name	City	State
Spain	Hospital de la Santa Creu I Sant Pau	Barcelona
Switzerland	Inselspital	Bern
Switzerland	Campus Biotech	Geneva
Switzerland	Geneva University Hospital	Geneva
Switzerland	Centre Hospitalier Universitaire Vaudois	Lausanne	Vaud
Switzerland	Hôpital du Valais	Sion

Sponsors (6)

Lead Sponsor	Collaborator
Olaf Blanke	Centre Hospitalier Universitaire Vaudois, Hôpital du Valais, Hospital de Sant Pau, University Hospital Inselspital, Berne, University Hospital, Geneva

Countries where clinical trial is conducted

Spain,  Switzerland, 

References & Publications (23)

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* Note: There are 23 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Sensitivity to the induction bodily illusions of Presence Hallucination, Passivity experiences, loss of agency, and control questions, through lab-tailored questionnaires (7-point Likert-scale)	Note that for the measuring the sensitivity of each patient to the induction of the presence hallucination, passivity sensations, loss of agency, and control questions, the patients will perform two manipulations with the robotic system described in the introduction, in both the synchronous and asynchronous conditions	5 minutes, at the end of each participant's session in arm 2
Primary	Sensitivity to the induction bodily illusions of Presence Hallucination, Passivity experiences, loss of agency, and control questions, through lab-tailored questionnaires (7-point Likert-scale) in the MRI scanner	After the sensorimotor task in the MRI scanner that induces the presence hallucination, ratings for the strength of the perceived sense of presence and associated phenomena are collected with the participants	5 minutes, at the end of each participant's session in arm 4
Primary	fMRI blood-oxygen level dependent signal response during resting state	We will analyse resting state data from the different populations of PD patients in this study and healthy controls	Approximately 30 minutes, during arm 3
Primary	fMRI blood-oxygen level dependent signal during robotic stimulation	We will analyse neural data from PH-induction inside the scanner, from the different populations of PD patients in this study and healthy controls	Approximately 45 minutes, during arm 4
Secondary	Dosage of dopaminergic medication (in daily equivalent mg/day)	Dosage of dopaminergic medication (in daily equivalent mg/day)	Approximately 10 minutes during screening
Secondary	Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS)	The Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale provides assessment of both motor and non-motor symptoms experienced by the patients during the last 7 days prior the examination. The scale comprise both self-report and semi-structured evaluations. The severity of each symptom is measured on a Likert-type scale from 0 (normal) to 4 (severe). Therefore the higher the score, the more impaired is the patient. The MDS-UPDRS has 50 items, categorised into four parts, namely, I: Non-motor experiences of daily living (range 0-52) II: Motor experiences of daily living (range 0-52) III: Motor examination (range 0-124) IV: Motor complications (range 0-24) I: Non-motor experiences of daily living II: Motor experiences of daily living III: Motor examination IV: Motor complications	15 minutes during arm 1
Secondary	Scale for the Assessment of Positive Symptoms (SAPS)	The SAPS is a validated clinical rating scale measuring positive symptoms of schizophrenia, recommended by the MDS to assess psychotic symptoms in PD, in the absence of a reliable validated one. The scale is sub-categorised into 4 domains within which specific symptoms are evaluated from 0 (absent) to 5 (severe): Hallucinations (67 items + 1 global evaluation item) (e.g., visual, auditory) (range 0-30); Delusions (12 items + 1 global evaluation item) (e.g., persecution, thought insertion) (range 0-60); Bizarre behaviour (4 items + 1 global evaluation item) (e.g., agitation, social behaviour) (range 0-20); Positive formal thought disorder (8 items+ 1 global evaluation item) (e.g., incoherence) (range 0-40) A composite score is calculated by adding the scores of each non-global item.. A global score of severity of symptoms with regard to duration and persistence of symptoms can be calculated by adding the scores of the global evaluation items.	15 minutes during arm 1
Secondary	Hallucination questionnaire specific for PD	This questionnaire is based on previous lab research and is a semi-structured interview on hallucinations and other psychotic symptoms. The frequency of symptoms is evaluated on a scale from 0 to 4. Two scoring systems are proposed to evaluate severity of symptoms (from 1-3): Severity score 1 refers to the impact of the symptoms on the patients' environment (ex: caregivers, family) as defined by the patients; Severity score 2 refers to the clinical severity as estimated by the clinician during the clinical interview. A composite score for each symptom is calculated: Frequency x Severity 1 (and Frequency x Severity 2). The composite scores of each symptom are then added to obtain the total score for the Category. The total score of the full scale is calculated by adding the total scores of Category A to E. The greater the score, the more frequent and severe the symptoms are.	15 minutes during arm 1
Secondary	The Hospital Anxiety and Depression Scale (HADS)	The Hospital Anxiety and Depression Scale is a 14-item self-assessment scale found to be a reliable instrument for detecting states of depression and anxiety. Seven items are dedicated to assess anxiety and the 7 others for depression on a 4-point Likert scale from 0 to 3.. A score > greater than 11/21 for each domain (anxiety or depression) indicates a considerable symptomatology for depression or anxiety.	5 minutes during arm 1
Secondary	REM Sleep Behaviour Disorder Screening Questionnaire (RBDSQ)	The REM Sleep Behaviour Disorder Screening Questionnaire is a self-report 13-item questionnaire assessing clinical features of REM sleep, and is a potential marker for PD. A "yes" (score 1) or "no" (score 0) is provided for each item. A maximum score of 13 indicates severe REM sleep behaviour disorders.	5 minutes during arm 1
Secondary	Beck Cognitive Insight Scale (BCIS)	a 15-item self-report questionnaire assessing the cognitive processes involved in the re-evaluation of anomalous experiences and their misinterpretations, i.e., distancing, objectivity, perspective, and self-correction. Subjects will rate on a scale from 0 (do not agree at all) to 3 (agree completely) how much they agree with each statement. A general insight ratio can also be calculated: self-reflectiveness sore/self-certainty score. High score reflects better cognitive insight (max=6).	3 minutes during arm 1
Secondary	UCLA loneliness questionnaire	This is a 3-item scale assessing the overall subjective feeling of loneliness in elderly populations from 1 (hardly) to 3 (often). A maximum score of 9 indicates the highest level of subjective feeling of loneliness.	2 minutes during arm 1
Secondary	Dimensional Apathy Scale (DAS)	The Dimensional Apathy Scale is a 24-item self-report questionnaire assessing three apathetic subtypes; namely cognitive, emotional-affective and auto-activation apathy. Subjects rate on a scale from 0 (almost always) to 3 (hardly ever) how much they agree with each statement. The scale provides the following sub-scores: (1) executive subscale, (2) emotional subscale and (3) behaviour/cognitive initiation subscale. A total score can be calculated. The maximum of each sub-scale is 24 and the total is 72. The cut-off score for each sub-scale are as follows: Executive: 14 Emotional: 15 Initiation: 16 Scoring below the cut-off indicates substantial clear apathetic symptoms.	5 minutes during arm 1
Secondary	Questionnaire for Impulsive-compulsive Disorders in Parkinson's Disease (QUIP)	The Questionnaire for Impulsive-compulsive Disorders in Parkinson's Disease self-rating assesses 7 major behaviours :1. Gambling, 2. Sex, 3. Buying, 4. Binge eating, 5. Hobbyism, 6. Punding and 7. Excessive medication use. Each behaviour is assessed by means of 4 questions on a Liket type scale from 0 (never) to 4 (very often). The scores of for each behaviour range from 0-16, and the total score to the scale ranges from 0-112. High scores reveal impulsive-compulsive disorders.	5 minutes during arm 1
Secondary	Neuropsychiatric Fluctuations Scale for Parkinson's Disease (NPS)	The Neuropsychiatric Fluctuations Scale for Parkinson's Disease is a 20-item self-report questionnaire. Ten items represent neuropsychiatric symptoms typically reported by patients in the OFF-medication condition and ten items measure neuropsychological symptoms typically reported by patients in the ON-medication condition. Subjects rate on a scale from 0 (no) to 3 (a lot) how much they agree with each statement. The scale provides two sub-scores, one for the ON-Items and one for the OFF-Items, ranging from 0-30. High scores indicate either ON-behaviours corresponding to ON-states (eg. euphoria, excitement) or OFF-states behaviours such as anxiety, lack of energy and fatigue.	5 minutes during arm 1
Secondary	Parkinson's disease - Cognitive Rating Scale (PD-CRS)	Parkinson's disease - Cognitive Rating Scale is a battery of neuropsychological tests specifically designed to capture the whole spectrum of cognitive impairment in patients with PD. This battery provides, as stated by the Movement Disorders Society: Frontal subcortical tasks (sustained attention, working memory, alternating and action verbal fluency, clock drawing, immediate and delayed free recall verbal memory). Scores range from 0-104.; Posterior cortical tasks (confrontation naming and clock copying), with scores ranging from 0 to 30.; Total scores range from 0-134 High scores are indicative of preserved cognitive functions.	25 minutes during arm 1
Secondary	Semantic and phonemic verbal fluency	Within 2 minutes, participants generate orally as many animal names as possible for the semantic fluency task, and as many words starting with letter P for the phonemic task, while respecting the following rules: no repetition and no word with the same root, and no proper nouns. The total number of words correctly named, and the number of errors are taken into account. Z-scores will be calculated.	4 minutes during arm 1
Secondary	Modified 5-point test (non-verbal fluency)	The test consists of squares containing 5 dots (like the number five on a dice). Participants are instructed to draw as many different patterns as possible, within 3 minutes, by connecting the dots by means of straight lines. The number of unique designs (maximum=80) and errors are counted. Z-scores will be calculated.	3 minutes during arm 1
Secondary	Trail Making Test A and B (TMT A; TMT B)	The Trail Making Test is a test during which the execution of the task is timed. The time taken to complete the test are noted as well as the number of errors. Z-scores will be calculated.Part A explores perceptual-motor speed (visuo-motor tracking) while part B requires more psychomotor speed and working memory.	maximum of 3 minutes during arm 1
Secondary	Symbol search	This sub-test, derived from the Wechsler Adult Intelligence Scale, assesses visuo-motor information processing speed within 2 minutes. Participants scan a search group and indicate whether one of the non-verbal symbols in the target group matches. The raw scores obtained are converted to standard scores with respect to participant's age. Cuff off of standard score = 10. Scores below 10 are considered under the normal range.	2 minutes during arm 1

External Links

•   Bernasconi F, Blondiaux E, Potheegadoo J, Stripeikyte G, ..., Blanke O. (2020) Sensorimotor hallucinations in Parkinson's Disease