Clinical trial NCT04592965: Hallucinations in Parkinson's Disease
Official title: Unravelling Dysfunctional Brain Networks in Patients With Parkinson's Disease Suffering From Hallucinations
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Parkinson Disease Psychosis
Keywords: Parkinson
fMRI
hallucinations
presence hallucination
sense of presence
connectivity
Lead sponsor: Ecole Polytechnique Fédérale de Lausanne
Sponsor class: OTHER
Collaborators: name: University Hospital, Geneva
name: Hôpital du Valais
name: Insel Gruppe AG, University Hospital Bern
name: Centre Hospitalier Universitaire Vaudois
name: Hospital de Sant Pau
First posted: 2020-10-19
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief 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

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.

Eligibility criteria: 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.

Primary outcomes:
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)
timeFrame: 5 minutes, at the end of each participant's session in arm 2
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) in the MRI scanner
timeFrame: 5 minutes, at the end of each participant's session in arm 4
measure: fMRI blood-oxygen level dependent signal response during resting state
timeFrame: Approximately 30 minutes, during arm 3
measure: fMRI blood-oxygen level dependent signal during robotic stimulation
timeFrame: Approximately 45 minutes, during arm 4
Secondary outcomes:
measure: Dosage of dopaminergic medication (in daily equivalent mg/day)
timeFrame: Approximately 10 minutes during screening
measure: Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS)
timeFrame: 15 minutes during arm 1
measure: Scale for the Assessment of Positive Symptoms (SAPS)
timeFrame: 15 minutes during arm 1
measure: Hallucination questionnaire specific for PD
timeFrame: 15 minutes during arm 1
measure: The Hospital Anxiety and Depression Scale (HADS)
timeFrame: 5 minutes during arm 1
measure: REM Sleep Behaviour Disorder Screening Questionnaire (RBDSQ)
timeFrame: 5 minutes during arm 1
measure: Beck Cognitive Insight Scale (BCIS)
timeFrame: 3 minutes during arm 1
measure: UCLA loneliness questionnaire
timeFrame: 2 minutes during arm 1
measure: Dimensional Apathy Scale (DAS)
timeFrame: 5 minutes during arm 1
measure: Questionnaire for Impulsive-compulsive Disorders in Parkinson's Disease (QUIP)
timeFrame: 5 minutes during arm 1
measure: Neuropsychiatric Fluctuations Scale for Parkinson's Disease (NPS)
timeFrame: 5 minutes during arm 1
measure: Parkinson's disease - Cognitive Rating Scale (PD-CRS)
timeFrame: 25 minutes during arm 1
measure: Semantic and phonemic verbal fluency
timeFrame: 4 minutes during arm 1
measure: Modified 5-point test (non-verbal fluency)
timeFrame: 3 minutes during arm 1
measure: Trail Making Test A and B (TMT A; TMT B)
timeFrame: maximum of 3 minutes during arm 1
measure: Symbol search
timeFrame: 2 minutes during arm 1
Other outcomes:
Locations:
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu I Sant Pau
city: Lausanne
country: Switzerland
facility: Centre Hospitalier Universitaire Vaudois
state: Vaud
city: Bern
country: Switzerland
facility: Inselspital
city: Geneva
country: Switzerland
facility: Campus Biotech
city: Geneva
country: Switzerland
facility: Geneva University Hospital
city: Sion
country: Switzerland
facility: Hôpital du Valais
Study officials:
affiliation: Ecole Polytechnique Fédérale de Lausanne
name: Olaf Blanke
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: Postuma 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.
citation: Wood 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.
citation: Ffytche 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.
citation: Diederich 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.
citation: Lenka 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.
citation: Fenelon 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.
citation: Blanke 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.
citation: Pagonabarraga 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.
citation: Goetz 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.
citation: Andreasen 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.
citation: Zigmond 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.
citation: Stiasny-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.
citation: Beck 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.
citation: Hughes 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.
citation: Radakovic R, Abrahams S. Developing a new apathy measurement scale: Dimensional Apathy Scale. Psychiatry Res. 2014 Nov 30;219(3):658-63. doi: 10.1016/j.psychres.2014.06.010. Epub 2014 Jun 19.
citation: Weintraub D, Hoops S, Shea JA, Lyons KE, Pahwa R, Driver-Dunckley ED, Adler CH, Potenza MN, Miyasaki J, Siderowf AD, Duda JE, Hurtig HI, Colcher A, Horn SS, Stern MB, Voon V. Validation of the questionnaire for impulsive-compulsive disorders in Parkinson's disease. Mov Disord. 2009 Jul 30;24(10):1461-7. doi: 10.1002/mds.22571.
citation: Schmitt E, Krack P, Castrioto A, Klinger H, Bichon A, Lhommee E, Pelissier P, Fraix V, Thobois S, Moro E, Martinez-Martin P. The Neuropsychiatric Fluctuations Scale for Parkinson's Disease: A Pilot Study. Mov Disord Clin Pract. 2018 Mar 23;5(3):265-272. doi: 10.1002/mdc3.12607. eCollection 2018 May-Jun.
citation: Pagonabarraga J, Kulisevsky J, Llebaria G, Garcia-Sanchez C, Pascual-Sedano B, Gironell A. Parkinson's disease-cognitive rating scale: a new cognitive scale specific for Parkinson's disease. Mov Disord. 2008 May 15;23(7):998-1005. doi: 10.1002/mds.22007.
citation: Ruff RM, Allen CC, Farrow CE, Niemann H, Wylie T. Figural fluency: differential impairment in patients with left versus right frontal lobe lesions. Arch Clin Neuropsychol. 1994 Jan;9(1):41-55.
citation: Reitan RM, Hom J, Wolfson D. Verbal processing by the brain. J Clin Exp Neuropsychol. 1988 Aug;10(4):400-8. doi: 10.1080/01688638808408248.
citation: Wechsler, D. (2008). Wechsler Adult Intelligence Scale (4th ed.). San Antonio, TX: Pearson Assessment
citation: Cardebat D, Demonet JF, Viallard G, Faure S, Puel M, Celsis P. Brain functional profiles in formal and semantic fluency tasks: a SPECT study in normals. Brain Lang. 1996 Feb;52(2):305-13. doi: 10.1006/brln.1996.0013.