Clinical trial NCT06349538: Identifying Markers of Disease Subtypes and Disease Progression in the Syndrome of Essential Tremor
Official title: Identifying Markers of Disease Subtypes and Disease Progression in the Syndrome of Essential Tremor - a Prospective Cohort Study
Study type: OBSERVATIONAL
Overall status: ENROLLING_BY_INVITATION
Conditions: Essential Tremor
Keywords: essential tremor
subtypes
neurodegeneration
biomarkers
MRI
imaging
sGFAP
sNfL
tremor analysis
Lead sponsor: Medical University of Graz
Sponsor class: OTHER
First posted: 2024-04-05
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: ET-patients will be recruited from all patients visiting a tertiary neurological hospital and its various institutions (emergency department, outpatient clinic, specialised outpatient clinic for movement disorders, ward patients) for any neurologic complaint.

Brief summary: The goal of this observational study is to learn about epidemiology, biologic markers, disease subtypes and possible prognostic factors in essential tremor (ET) patients. The main question\[s\] it aims to answer are:

* The prevalence of ET-plus compared to ET in a prospectively collected ET population.
* To assess in detail the heterogenous group of ET patients using comprehensive clinical (motor and non-motor scales, questionnaires), imaging \[magnetic resonance imaging (MRI), sonography of substantia nigra and cerebral vessels\], neurophysiological (tremor analysis, digital spiral drawing) and laboratory markers (sGFAP, sNfL, routine laboratory parameters).
* To assess possible non-invasive markers of neurodegeneration in ET patients (optic coherence tomography, alpha-synuclein in olfactory mucosa)

Participants will be asked to undergo the above mention evaluation at baseline and at follow-up approx. 5 years later.

Researchers will compare the findings within the ET group to independently existing cohorts of healthy controls and/or patients with other movement disorders like Parkinson's disease.


Eligibility criteria: Inclusion Criteria:

* Presence of an essential tremor syndrome according to MDS consensus criteria or suspected incipient essential tremor (differential diagnosis vs. enhanced physiological tremor)
* Patient is able and willing to give informed consent.
* age above 18 years.

Exclusion Criteria:

* Patient is not able or not willing to give informed consent.
* Existence of a legal representative.
* age below 18 years

Primary outcomes:
measure: Prevalence of ET-plus
timeFrame: approx. 2 years
Secondary outcomes:
measure: Age of ET patients
timeFrame: 1 minute; Baseline (recruiting time approx. 2 years) and follow-up (5 years after individual baseline)
measure: Sex of ET patients
timeFrame: 1 minute; Baseline (recruiting time approx. 2 years) and follow-up (5 years after individual baseline)
measure: Family history
timeFrame: 1 minute; Baseline (recruiting time approx. 2 years) and follow-up (5 years after individual baseline)
measure: Symptom leading to ET-plus classification
timeFrame: 1 minute; Baseline (recruiting time approx. 2 years) and follow-up (5 years after individual baseline)
measure: current and former medication for essential tremor
timeFrame: 2 minutes; Baseline (recruiting time approx. 2 years) and follow-up (5 years after individual baseline)
measure: subjective disease course of ET
timeFrame: 1 minute; Baseline (recruiting time approx. 2 years) and follow-up (5 years after individual baseline)
measure: responsivity to alcohol
timeFrame: 1 minutes; Baseline (recruiting time approx. 2 years) and follow-up (5 years after individual baseline)
measure: presence of cardiovascular risk factors
timeFrame: 2 minutes; Baseline (recruiting time approx. 2 years) and follow-up (5 years after individual baseline)
measure: MDS-UPDRS (Movement Disorder Society Unified Parkinson's Disease Rating Scale) parts I-IV
timeFrame: 20-30 minutes; Baseline (recruiting time approx. 2 years) and follow-up (5 years after individual baseline)
measure: modified Essential Tremor Rating Assessment Scale (mTETRAS)
timeFrame: 10 minutes; Baseline (recruiting time approx. 2 years) and follow-up (5 years after individual baseline)
measure: Scale for the assessment and rating of ataxia (SARA)
timeFrame: 5-10 minutes; Baseline (recruiting time approx. 2 years) and follow-up (5 years after individual baseline)
measure: Verbal fluency animals (part of the CERAD-plus test battery)
timeFrame: 1 minute; Baseline (recruiting time approx. 2 years) and follow-up (5 years after individual baseline)
measure: Boston Naming Test (part of the CERAD-plus test battery)
timeFrame: 2 minutes; Baseline (recruiting time approx. 2 years) and follow-up (5 years after individual baseline)
measure: Mini Mental State Examination Test (MMSE; part of the CERAD-plus test battery)
timeFrame: 3-5 minutes; Baseline (recruiting time approx. 2 years) and follow-up (5 years after individual baseline)
measure: word list learning (part of the CERAD-plus test battery)
timeFrame: 10 minutes; Baseline (recruiting time approx. 2 years) and follow-up (5 years after individual baseline)
measure: constructive praxis (part of the CERAD-plus test battery)
timeFrame: 20-30 minutes; Baseline (recruiting time approx. 2 years) and follow-up (5 years after individual baseline)
measure: word list recall (part of the CERAD-plus test battery)
timeFrame: 90 seconds; Baseline (recruiting time approx. 2 years) and follow-up (5 years after individual baseline)
measure: word list recognition (part of the CERAD-plus test battery)
timeFrame: 2 minutes; Baseline (recruiting time approx. 2 years) and follow-up (5 years after individual baseline)
measure: constructive praxis recall (part of the CERAD-plus test battery)
timeFrame: 3-4 minutes; Baseline (recruiting time approx. 2 years) and follow-up (5 years after individual baseline)
measure: Trail Making Test A (part of the CERAD-plus test battery)
timeFrame: 2 minutes; Baseline (recruiting time approx. 2 years) and follow-up (5 years after individual baseline)
measure: Trail Making Test B (part of the CERAD-plus test battery)
timeFrame: 2 minutes; Baseline (recruiting time approx. 2 years) and follow-up (5 years after individual baseline)
measure: s-words (part of the CERAD-plus test battery)
timeFrame: 1 minute; Baseline (recruiting time approx. 2 years) and follow-up (5 years after individual baseline)
measure: Frontal Assessment Battery (FAB)
timeFrame: 5 - 10 minutes; Baseline (recruiting time approx. 2 years) and follow-up (5 years after individual baseline)
measure: Geriatric Depression Scale (GDS)
timeFrame: 3-5 minutes; Baseline (recruiting time approx. 2 years) and follow-up (5 years after individual baseline)
measure: Hospital Anxiety and Depression Scale (HADS)
timeFrame: 5 minutes; Baseline (recruiting time approx. 2 years) and follow-up (5 years after individual baseline)
measure: Non-Motor Symptoms Scale for Parkinson's Disease (NMSS)
timeFrame: 5 minutes; Baseline (recruiting time approx. 2 years) and follow-up (5 years after individual baseline)
measure: RBD Screening Questionnaire
timeFrame: 2 minutes; Baseline (recruiting time approx. 2 years) and follow-up (5 years after individual baseline)
measure: Global Physical Activity Questionnaire (GPAQ)
timeFrame: 5-7 minutes; Baseline (recruiting time approx. 2 years) and follow-up (5 years after individual baseline)
measure: Quality of Life in Essential Tremor Questionnaire (QUEST)
timeFrame: 5 minutes; Baseline (recruiting time approx. 2 years) and follow-up (5 years after individual baseline)
measure: University of Pennsylvania Smell Identification Test (UPSIT)
timeFrame: 10-15 minutes; Baseline (recruiting time approx. 2 years) and follow-up (5 years after individual baseline)
measure: Montreal Cognitive Assessment (MOCA)
timeFrame: 5-10 minutes; Baseline (recruiting time approx. 2 years) and follow-up (5 years after individual baseline)
measure: Auditory verbal learning test
timeFrame: 5 minutes; Baseline (recruiting time approx. 2 years) and follow-up (5 years after individual baseline)
measure: Symbol Digit Modalities Test (SDMT)
timeFrame: 90 seconds; Baseline (recruiting time approx. 2 years) and follow-up (5 years after individual baseline)
measure: Brief Visuospatial Memory Test
timeFrame: 2-3 minutes; Baseline (recruiting time approx. 2 years) and follow-up (5 years after individual baseline)
measure: Comprehensive trail making test 4
timeFrame: 1-2 minutes; Baseline (recruiting time approx. 2 years) and follow-up (5 years after individual baseline)
measure: Comprehensive trail making test 5
timeFrame: 1-2 minutes; Baseline (recruiting time approx. 2 years) and follow-up (5 years after individual baseline)
measure: Regensburg word fluency test
timeFrame: 2 minutes; Baseline (recruiting time approx. 2 years) and follow-up (5 years after individual baseline)
measure: EQ-5D
timeFrame: 1-2 minutes; Baseline (recruiting time approx. 2 years) and follow-up (5 years after individual baseline)
measure: resilience scale (RS-13)
timeFrame: 1-2 minutes; Baseline (recruiting time approx. 2 years) and follow-up (5 years after individual baseline)
measure: Pittsburgh Sleep Quality Index (PSQI)
timeFrame: 3-4 minutes; Baseline (recruiting time approx. 2 years) and follow-up (5 years after individual baseline)
measure: Digital Spiral Drawing
timeFrame: 2-3 minutes; Baseline (recruiting time approx. 2 years) and follow-up (5 years after individual baseline)
measure: Schellong Test
timeFrame: 3.5 minutes; Baseline (recruiting time approx. 2 years) and follow-up (5 years after individual baseline)
measure: serum glial fibrillary acidic protein (sGFAP)
timeFrame: 5 minutes; Baseline (recruiting time approx. 2 years) and follow-up (5 years after individual baseline)
measure: serum neurofilament light (sNfL)
timeFrame: 5 minutes; Baseline (recruiting time approx. 2 years) and follow-up (5 years after individual baseline)
measure: Transcranial sonography
timeFrame: 10 minutes; Baseline (recruiting time approx. 2 years) and follow-up (5 years after individual baseline)
measure: tremor analysis
timeFrame: 20 minutes; Baseline (recruiting time approx. 2 years) and follow-up (5 years after individual baseline)
measure: cerebral MRI
timeFrame: 45 minutes; Baseline (recruiting time approx. 2 years) and follow-up (5 years after individual baseline)
measure: cerebral MRI
timeFrame: 45 minutes; Baseline (recruiting time approx. 2 years) and follow-up (5 years after individual baseline)
measure: cerebral MRI
timeFrame: 45 minutes; Baseline (recruiting time approx. 2 years) and follow-up (5 years after individual baseline)
measure: cerebral MRI
timeFrame: 45 minutes; Baseline (recruiting time approx. 2 years) and follow-up (5 years after individual baseline)
measure: cerebral MRI
timeFrame: 45 minutes; Baseline (recruiting time approx. 2 years) and follow-up (5 years after individual baseline)
measure: cerebral MRI
timeFrame: 45 minutes; Baseline (recruiting time approx. 2 years) and follow-up (5 years after individual baseline)
measure: optic coherence tomography (OCT)
timeFrame: 5-10 minutes; Baseline (recruiting time approx. 2 years) and follow-up (5 years after individual baseline)
measure: optic coherence tomography (OCT)
timeFrame: 5-10 minutes; Baseline (recruiting time approx. 2 years) and follow-up (5 years after individual baseline)
measure: optic coherence tomography (OCT)
timeFrame: 5-10 minutes; Baseline (recruiting time approx. 2 years) and follow-up (5 years after individual baseline)
measure: optic coherence tomography (OCT)
timeFrame: 5-10 minutes; Baseline (recruiting time approx. 2 years) and follow-up (5 years after individual baseline)
measure: Olfactory mucosa swab
timeFrame: 5-10 minutes; Baseline (recruiting time approx. 2 years) and follow-up (5 years after individual baseline)
Other outcomes:
Locations:
city: Graz
country: Austria
facility: Medical University of Graz
Study officials:
References:
citation: Bhatia KP, Bain P, Bajaj N, Elble RJ, Hallett M, Louis ED, Raethjen J, Stamelou M, Testa CM, Deuschl G; Tremor Task Force of the International Parkinson and Movement Disorder Society. Consensus Statement on the classification of tremors. from the task force on tremor of the International Parkinson and Movement Disorder Society. Mov Disord. 2018 Jan;33(1):75-87. doi: 10.1002/mds.27121. Epub 2017 Nov 30.
citation: Doustar J, Torbati T, Black KL, Koronyo Y, Koronyo-Hamaoui M. Optical Coherence Tomography in Alzheimer's Disease and Other Neurodegenerative Diseases. Front Neurol. 2017 Dec 19;8:701. doi: 10.3389/fneur.2017.00701. eCollection 2017.
citation: Stefani A, Iranzo A, Holzknecht E, Perra D, Bongianni M, Gaig C, Heim B, Serradell M, Sacchetto L, Garrido A, Capaldi S, Sanchez-Gomez A, Cecchini MP, Mariotto S, Ferrari S, Fiorini M, Schmutzhard J, Cocchiara P, Vilaseca I, Brozzetti L, Monaco S, Jose Marti M, Seppi K, Tolosa E, Santamaria J, Hogl B, Poewe W, Zanusso G; SINBAR (Sleep Innsbruck Barcelona) group. Alpha-synuclein seeds in olfactory mucosa of patients with isolated REM sleep behaviour disorder. Brain. 2021 May 7;144(4):1118-1126. doi: 10.1093/brain/awab005.