Parkinson Disease PsychosisNCT04592965
Hallucinations in Parkinson's Disease
A study testing Clinical and neuropsychological assessments, Induction of PH and associated bodily states and Resting-state fMRI acquisition in people with Parkinson Disease Psychosis, run by Olaf Blanke at 6 sites in 2 countries.
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 Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Parkinson Disease Psychosis
- What is being tested?
- Clinical and neuropsychological assessments, Induction of PH and associated bodily states and Resting-state fMRI acquisition
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 6 sitesin 2 countries
- Study dates
- 17 Aug 2020to 1 Dec 2021
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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).
Show all 11Show fewer
- 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.
Trial locations and contacts
6 sites in 2 countries.
6 sites in 2 countries
Switzerland5 sites, 4 recruiting
- Recruiting
Inselspital
Bern, 1310
Paul Krack, +41 21 664 03 71, paul.krack@insel.ch
Paul Krack
- Active, not recruiting
Campus Biotech
Geneva, 1202
- Recruiting
Geneva University Hospital
Geneva, 1202
Pierre Burkhard, +41 22 372 83 18, pierre.burkhard@hcuge.ch
Pierre Burkhrad
- Not yet recruiting
Centre Hospitalier Universitaire Vaudois
Lausanne, Canton of Vaud, 1011
David Benninger, +41 21 314 1 90, david.bennigner@chuv.ch
David Bennigner
- Recruiting
Hôpital du Valais
Sion, 1951
Joseph-André Ghika, +41 27 603 40 89, joseph-andre.ghika@hopitalvs.ch
Joseph-André Ghika
Spain1 site, 1 recruiting
- Not yet recruiting
Hospital de la Santa Creu I Sant Pau
Barcelona, 08041
Jaime Kulisevsky, +34 935565986, JKulisevsky@santpau.cat
Javier Pagonabarraga, +34 647618844, JPagonabarraga@santpau.cat
About this study
Official title: Unravelling Dysfunctional Brain Networks in Patients With Parkinson's Disease Suffering From Hallucinations
Investigation on how robotically mediated sensorimotor stimulation induces and triggers presence hallucinations in different clinical groups of parkinsonian patients, and in aged-matched controls
Read the detailed 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.
- Conditions
- Parkinson Disease Psychosis
- Being tested
- Clinical and neuropsychological assessments, Induction of PH and associated bodily states, Resting-state fMRI acquisition, Induction of PH and associated bodily states (MRI)
- Keywords
- Parkinson, fMRI, hallucinations, presence hallucination, sense of presence, connectivity
- Medical subject headings
- Hallucinations
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Clinical and neuropsychological assessmentsBehavioural
The assessment of disease state, clinical condition, and of cognitive and neuropsychological attributes.
Induction of PH and associated bodily statesBehavioural
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
Resting-state fMRI acquisitionOther
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)Other
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
| Study group | Role | What they receive |
|---|---|---|
| Clinical and neuropsychological examinations | Experimental | Participants will be assessed by means of validated and lab-tailored clinical scales, alongside with semi-structured interviews, to assess the status of the disease (PD), amongst others, such as cognitive capabilities. Receives: Behavioral: Clinical and neuropsychological assessments |
| Robot induced PH, through sensorimotor stimulation | Experimental | Participants will manipulate a patented robotic system designed to induce the PH and other accompanying bodily illusions. At the end, participants will report on various subjective experiences, by answering a structured questionnaire. Receives: Behavioral: Induction of PH and associated bodily states |
| Resting-state fMRI acquistion | Experimental | We will acquire resting-state data in the MRI scanner for all the participants. Respiration and heart beat rate data will also be acquired. Receives: Other: Resting-state fMRI acquisition |
| Robot induced PH, through sensorimotor stimulation (MRI) | Experimental | All healthy participants, and all patients who are deemed capable of performing the robotic manipulation task in the MRI scanner, will take part on this arm. Participants will perform a robotic manipulation task, with a patented robotic system, capable of inducing the PH and other accompanying bodily illusions in the MRI scanner. At the end participants will report on the various subjective experiences, by answering a structured questionnaire. Receives: Other: Induction of PH and associated bodily states (MRI) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 5 minutes, at the end of each participant's session in arm 2
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
Measured: 5 minutes, at the end of each participant's session in arm 4
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
Measured: Approximately 30 minutes, during arm 3
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
Measured: Approximately 45 minutes, during arm 4
Secondary outcomes (16)
Dosage of dopaminergic medication (in daily equivalent mg/day)
Dosage of dopaminergic medication (in daily equivalent mg/day)
Measured: Approximately 10 minutes during screening
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
Measured: 15 minutes during arm 1
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.
Measured: 15 minutes during arm 1
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.
Measured: 15 minutes during arm 1
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.
Measured: 5 minutes during arm 1
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.
Measured: 5 minutes during arm 1
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).
Measured: 3 minutes during arm 1
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.
Measured: 2 minutes during arm 1
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.
Measured: 5 minutes during arm 1
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.
Measured: 5 minutes during arm 1
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.
Measured: 5 minutes during arm 1
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.
Measured: 25 minutes during arm 1
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.
Measured: 4 minutes during arm 1
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.
Measured: 3 minutes during arm 1
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.
Measured: maximum of 3 minutes during arm 1
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.
Measured: 2 minutes during arm 1
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Oct 2020
- Study start17 Aug 2020
- Primary completion1 Dec 2021 (estimated)
- Study completion1 Dec 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (23)Papers the sponsor has linked to this study.
- Other trials for Parkinson Disease PsychosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Olaf Blanke
- Sponsor type
- University, hospital or other
- Collaborators
- University Hospital, Geneva, Hôpital du Valais, Insel Gruppe AG, University Hospital Bern, Centre Hospitalier Universitaire Vaudois, Hospital de Sant Pau
- Responsible party
- Sponsor-investigator, Olaf Blanke, Ecole Polytechnique Fédérale de Lausanne
- Investigators
- Olaf Blanke, Principal investigator, Ecole Polytechnique Fédérale de Lausanne
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04592965
- Sponsor's protocol ID
- UH_PD
- Status last verified
- Oct 2020
- First submitted
- 15 Jul 2020
- Last updated
- 19 Oct 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Kalia LV, Lang AE. Parkinson's disease. Lancet. 2015 Aug 29;386(9996):896-912. doi: 10.1016/S0140-6736(14)61393-3. Epub 2015 Apr 19.
PubMed 25904081Postuma RB, Berg D. Advances in markers of prodromal Parkinson disease. Nat Rev Neurol. 2016 Oct 27;12(11):622-634. doi: 10.1038/nrneurol.2016.152.
PubMed 27786242Wood RA, Hopkins SA, Moodley KK, Chan D. Fifty Percent Prevalence of Extracampine Hallucinations in Parkinson's Disease Patients. Front Neurol. 2015 Dec 21;6:263. doi: 10.3389/fneur.2015.00263. eCollection 2015.
PubMed 26733937Ffytche DH, Aarsland D. Psychosis in Parkinson's Disease. Int Rev Neurobiol. 2017;133:585-622. doi: 10.1016/bs.irn.2017.04.005. Epub 2017 Jun 16.
PubMed 28802934Diederich NJ, Fenelon G, Stebbins G, Goetz CG. Hallucinations in Parkinson disease. Nat Rev Neurol. 2009 Jun;5(6):331-42. doi: 10.1038/nrneurol.2009.62.
PubMed 19498436Lenka A, Pagonabarraga J, Pal PK, Bejr-Kasem H, Kulisevsky J. Minor hallucinations in Parkinson disease: A subtle symptom with major clinical implications. Neurology. 2019 Aug 6;93(6):259-266. doi: 10.1212/WNL.0000000000007913. Epub 2019 Jul 9.
PubMed 31289146Fenelon G, Soulas T, Cleret de Langavant L, Trinkler I, Bachoud-Levi AC. Feeling of presence in Parkinson's disease. J Neurol Neurosurg Psychiatry. 2011 Nov;82(11):1219-24. doi: 10.1136/jnnp.2010.234799. Epub 2011 May 7.
PubMed 21551471Blanke O, Pozeg P, Hara M, Heydrich L, Serino A, Yamamoto A, Higuchi T, Salomon R, Seeck M, Landis T, Arzy S, Herbelin B, Bleuler H, Rognini G. Neurological and robot-controlled induction of an apparition. Curr Biol. 2014 Nov 17;24(22):2681-6. doi: 10.1016/j.cub.2014.09.049. Epub 2014 Nov 6.
PubMed 25447995Pagonabarraga J, Soriano-Mas C, Llebaria G, Lopez-Sola M, Pujol J, Kulisevsky J. Neural correlates of minor hallucinations in non-demented patients with Parkinson's disease. Parkinsonism Relat Disord. 2014 Mar;20(3):290-6. doi: 10.1016/j.parkreldis.2013.11.017. Epub 2013 Dec 10.
PubMed 24373690Goetz CG, Tilley BC, Shaftman SR, Stebbins GT, Fahn S, Martinez-Martin P, Poewe W, Sampaio C, Stern MB, Dodel R, Dubois B, Holloway R, Jankovic J, Kulisevsky J, Lang AE, Lees A, Leurgans S, LeWitt PA, Nyenhuis D, Olanow CW, Rascol O, Schrag A, Teresi JA, van Hilten JJ, LaPelle N; Movement Disorder Society UPDRS Revision Task Force. Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS): scale presentation and clinimetric testing results. Mov Disord. 2008 Nov 15;23(15):2129-70. doi: 10.1002/mds.22340.
PubMed 19025984Andreasen NC, Arndt S, Miller D, Flaum M, Nopoulos P. Correlational studies of the Scale for the Assessment of Negative Symptoms and the Scale for the Assessment of Positive Symptoms: an overview and update. Psychopathology. 1995;28(1):7-17. doi: 10.1159/000284894.
PubMed 7871123Zigmond AS, Snaith RP. The hospital anxiety and depression scale. Acta Psychiatr Scand. 1983 Jun;67(6):361-70. doi: 10.1111/j.1600-0447.1983.tb09716.x.
PubMed 6880820Stiasny-Kolster K, Mayer G, Schafer S, Moller JC, Heinzel-Gutenbrunner M, Oertel WH. The REM sleep behavior disorder screening questionnaire--a new diagnostic instrument. Mov Disord. 2007 Dec;22(16):2386-93. doi: 10.1002/mds.21740.
PubMed 17894337Beck AT, Baruch E, Balter JM, Steer RA, Warman DM. A new instrument for measuring insight: the Beck Cognitive Insight Scale. Schizophr Res. 2004 Jun 1;68(2-3):319-29. doi: 10.1016/S0920-9964(03)00189-0.
PubMed 15099613Hughes ME, Waite LJ, Hawkley LC, Cacioppo JT. A Short Scale for Measuring Loneliness in Large Surveys: Results From Two Population-Based Studies. Res Aging. 2004;26(6):655-672. doi: 10.1177/0164027504268574.
PubMed 18504506
Study at a glance
From the registry record, last updated by the sponsor on 19 Oct 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Unravelling Dysfunctional Brain Networks in Patients With Parkinson's Disease Suffering From Hallucinations
- ClinicalTrials.gov ID
- NCT04592965
- Acronym / sponsor ID
- UH_PD
- Conditions
- Parkinson Disease Psychosis
- Keywords
- Parkinson, fMRI, hallucinations, presence hallucination, sense of presence, connectivity
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- Olaf BlankeUniversity, hospital or other
- Collaborators
- University Hospital, Geneva, Hôpital du Valais, Insel Gruppe AG, University Hospital Bern, Centre Hospitalier Universitaire Vaudois, Hospital de Sant Pau
- Study start
- 17 Aug 2020 (actual)
- Primary completion
- 1 Dec 2021 (estimated)
- Study completion
- 1 Dec 2021 (estimated)
- First posted
- 19 Oct 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Investigation on how robotically mediated sensorimotor stimulation induces and triggers presence hallucinations in different clinical groups of parkinsonian patients, and in aged-matched controls
Detailed 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.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Clinical and neuropsychological examinations | Experimental | Behavioral: Clinical and neuropsychological assessmentsParticipants will be assessed by means of validated and lab-tailored clinical scales, alongside with semi-structured interviews, to assess the status of the disease (PD), amongst others, such as cognitive capabilities. |
| Robot induced PH, through sensorimotor stimulation | Experimental | Behavioral: Induction of PH and associated bodily statesParticipants will manipulate a patented robotic system designed to induce the PH and other accompanying bodily illusions. At the end, participants will report on various subjective experiences, by answering a structured questionnaire. |
| Resting-state fMRI acquistion | Experimental | Other: Resting-state fMRI acquisitionWe will acquire resting-state data in the MRI scanner for all the participants. Respiration and heart beat rate data will also be acquired. |
| Robot induced PH, through sensorimotor stimulation (MRI) | Experimental | Other: Induction of PH and associated bodily states (MRI)All healthy participants, and all patients who are deemed capable of performing the robotic manipulation task in the MRI scanner, will take part on this arm. Participants will perform a robotic manipulation task, with a patented robotic system, capable of inducing the PH and other accompanying bodily illusions in the MRI scanner. At the end participants will report on the various subjective experiences, by answering a structured questionnaire. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (11 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Clinical and neuropsychological assessmentsThe assessment of disease state, clinical condition, and of cognitive and neuropsychological attributes. | Behavioural | Clinical and neuropsychological examinations |
| Induction of PH and associated bodily statesAssessment of subjective sensitivity to the induction of the PH and associated bodily states, for different populations of PD patients and healthy aged-matched controls | Behavioural | Robot induced PH, through sensorimotor stimulation |
| Resting-state fMRI acquisitionInvestigation 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 | Other | Resting-state fMRI acquistion |
| 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 | Other | Robot induced PH, through sensorimotor stimulation (MRI) |
Primary outcome
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)
Time frame: 5 minutes, at the end of each participant's session in arm 2
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
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
Time frame: 5 minutes, at the end of each participant's session in arm 4
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
fMRI blood-oxygen level dependent signal response during resting state
Time frame: Approximately 30 minutes, during arm 3
We will analyse resting state data from the different populations of PD patients in this study and healthy controls
fMRI blood-oxygen level dependent signal during robotic stimulation
Time frame: Approximately 45 minutes, during arm 4
We will analyse neural data from PH-induction inside the scanner, from the different populations of PD patients in this study and healthy controls
16 secondary outcomes
Dosage of dopaminergic medication (in daily equivalent mg/day)
Time frame: Approximately 10 minutes during screening
Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS)
Time frame: 15 minutes during arm 1
Scale for the Assessment of Positive Symptoms (SAPS)
Time frame: 15 minutes during arm 1
Hallucination questionnaire specific for PD
Time frame: 15 minutes during arm 1
The Hospital Anxiety and Depression Scale (HADS)
Time frame: 5 minutes during arm 1
REM Sleep Behaviour Disorder Screening Questionnaire (RBDSQ)
Time frame: 5 minutes during arm 1
Beck Cognitive Insight Scale (BCIS)
Time frame: 3 minutes during arm 1
UCLA loneliness questionnaire
Time frame: 2 minutes during arm 1
Dimensional Apathy Scale (DAS)
Time frame: 5 minutes during arm 1
Questionnaire for Impulsive-compulsive Disorders in Parkinson's Disease (QUIP)
Time frame: 5 minutes during arm 1
Neuropsychiatric Fluctuations Scale for Parkinson's Disease (NPS)
Time frame: 5 minutes during arm 1
Parkinson's disease - Cognitive Rating Scale (PD-CRS)
Time frame: 25 minutes during arm 1
Semantic and phonemic verbal fluency
Time frame: 4 minutes during arm 1
Modified 5-point test (non-verbal fluency)
Time frame: 3 minutes during arm 1
Trail Making Test A and B (TMT A; TMT B)
Time frame: maximum of 3 minutes during arm 1
Symbol search
Time frame: 2 minutes during arm 1
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Oct 2020.
- Background: PubMed 25904081Kalia LV, Lang AE. Parkinson's disease. Lancet. 2015 Aug 29;386(9996):896-912. doi: 10.1016/S0140-6736(14)61393-3. Epub 2015 Apr 19.
- Background: PubMed 27786242Postuma RB, Berg D. Advances in markers of prodromal Parkinson disease. Nat Rev Neurol. 2016 Oct 27;12(11):622-634. doi: 10.1038/nrneurol.2016.152.
- Background: PubMed 26733937Wood RA, Hopkins SA, Moodley KK, Chan D. Fifty Percent Prevalence of Extracampine Hallucinations in Parkinson's Disease Patients. Front Neurol. 2015 Dec 21;6:263. doi: 10.3389/fneur.2015.00263. eCollection 2015.
- Background: PubMed 28802934Ffytche DH, Aarsland D. Psychosis in Parkinson's Disease. Int Rev Neurobiol. 2017;133:585-622. doi: 10.1016/bs.irn.2017.04.005. Epub 2017 Jun 16.
- Background: PubMed 19498436Diederich NJ, Fenelon G, Stebbins G, Goetz CG. Hallucinations in Parkinson disease. Nat Rev Neurol. 2009 Jun;5(6):331-42. doi: 10.1038/nrneurol.2009.62.
- Background: PubMed 31289146Lenka A, Pagonabarraga J, Pal PK, Bejr-Kasem H, Kulisevsky J. Minor hallucinations in Parkinson disease: A subtle symptom with major clinical implications. Neurology. 2019 Aug 6;93(6):259-266. doi: 10.1212/WNL.0000000000007913. Epub 2019 Jul 9.
- Background: PubMed 21551471Fenelon G, Soulas T, Cleret de Langavant L, Trinkler I, Bachoud-Levi AC. Feeling of presence in Parkinson's disease. J Neurol Neurosurg Psychiatry. 2011 Nov;82(11):1219-24. doi: 10.1136/jnnp.2010.234799. Epub 2011 May 7.
- Background: PubMed 25447995Blanke O, Pozeg P, Hara M, Heydrich L, Serino A, Yamamoto A, Higuchi T, Salomon R, Seeck M, Landis T, Arzy S, Herbelin B, Bleuler H, Rognini G. Neurological and robot-controlled induction of an apparition. Curr Biol. 2014 Nov 17;24(22):2681-6. doi: 10.1016/j.cub.2014.09.049. Epub 2014 Nov 6.
- Background: PubMed 24373690Pagonabarraga J, Soriano-Mas C, Llebaria G, Lopez-Sola M, Pujol J, Kulisevsky J. Neural correlates of minor hallucinations in non-demented patients with Parkinson's disease. Parkinsonism Relat Disord. 2014 Mar;20(3):290-6. doi: 10.1016/j.parkreldis.2013.11.017. Epub 2013 Dec 10.
- Background: PubMed 19025984Goetz CG, Tilley BC, Shaftman SR, Stebbins GT, Fahn S, Martinez-Martin P, Poewe W, Sampaio C, Stern MB, Dodel R, Dubois B, Holloway R, Jankovic J, Kulisevsky J, Lang AE, Lees A, Leurgans S, LeWitt PA, Nyenhuis D, Olanow CW, Rascol O, Schrag A, Teresi JA, van Hilten JJ, LaPelle N; Movement Disorder Society UPDRS Revision Task Force. Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS): scale presentation and clinimetric testing results. Mov Disord. 2008 Nov 15;23(15):2129-70. doi: 10.1002/mds.22340.
- Background: PubMed 7871123Andreasen NC, Arndt S, Miller D, Flaum M, Nopoulos P. Correlational studies of the Scale for the Assessment of Negative Symptoms and the Scale for the Assessment of Positive Symptoms: an overview and update. Psychopathology. 1995;28(1):7-17. doi: 10.1159/000284894.
- Background: PubMed 6880820Zigmond AS, Snaith RP. The hospital anxiety and depression scale. Acta Psychiatr Scand. 1983 Jun;67(6):361-70. doi: 10.1111/j.1600-0447.1983.tb09716.x.
- Bernasconi F, Blondiaux E, Potheegadoo J, Stripeikyte G, ..., Blanke O. (2020) Sensorimotor hallucinations in Parkinson's DiseaseLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Olaf Blanke principal investigator
Ecole Polytechnique Fédérale de Lausanne
6 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Clinical and neuropsychological assessments, Induction of PH and associated bodily states and Resting-state fMRI acquisition in people with Parkinson Disease Psychosis, run by Olaf Blanke at 6 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 19 Oct 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in Switzerland, Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Olaf Blanke (+41 21 693 9621, olaf.blanke@epfl.ch), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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) (time frame: 5 minutes, at the end of each participant's session in arm 2). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04592965, which also lists 23 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Oct 2020.