Identifying Markers of Disease Subtypes and Disease Progression in the Syndrome of Essential Tremor

Essential Tremor Clinical Trial

Official title:

Identifying Markers of Disease Subtypes and Disease Progression in the Syndrome of Essential Tremor - a Prospective Cohort Study

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT06349538
• Other study ID #: 35-435 ex 22/23
• Status: Enrolling by invitation
• Start date: April 4, 2024
• Est. completion date: April 30, 2034

Study information

• Verified date: March 2024
• Source: Medical University of Graz
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 100
• Est. completion date: April 30, 2034
• Est. primary completion date: April 30, 2026
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Disease Progression
• Essential Tremor
• Tremor

Intervention

Diagnostic Test:
• Clinical examination, blood draw, cerebral MRI, sonography, tremor analysis, OCT, olfactory mucosa swab.
see previous descriptions

Locations

Country	Name	City	State
Austria	Medical University of Graz	Graz

Sponsors (1)

Lead Sponsor	Collaborator
Medical University of Graz

Country where clinical trial is conducted

Austria, 

References & Publications (3)

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. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Prevalence of ET-plus	Determine the prevalence of ET-plus within a prospectively collected ET population	approx. 2 years
Secondary	Age of ET patients	age at disease onset and age at baseline	1 minute; Baseline (recruiting time approx. 2 years) and follow-up (5 years after individual baseline)
Secondary	Sex of ET patients	male, female, other	1 minute; Baseline (recruiting time approx. 2 years) and follow-up (5 years after individual baseline)
Secondary	Family history	positive or negative for essential tremor or Parkinson's disease	1 minute; Baseline (recruiting time approx. 2 years) and follow-up (5 years after individual baseline)
Secondary	Symptom leading to ET-plus classification	e.g. rest tremor, impaired tandem gait, mild parkinsonian signs, questionable dystonia, mild cognitive impairment	1 minute; Baseline (recruiting time approx. 2 years) and follow-up (5 years after individual baseline)
Secondary	current and former medication for essential tremor	e.g. propranolol yes vs no, topiramate yes vs no, primidone yes vs no	2 minutes; Baseline (recruiting time approx. 2 years) and follow-up (5 years after individual baseline)
Secondary	subjective disease course of ET	no progression, slowly and continuously, relapsing, plateau-like after initial progression, rapidly progressive	1 minute; Baseline (recruiting time approx. 2 years) and follow-up (5 years after individual baseline)
Secondary	responsivity to alcohol	amelioration of tremor severity after consumption of alcohol (yes vs. no vs. unknown)	1 minutes; Baseline (recruiting time approx. 2 years) and follow-up (5 years after individual baseline)
Secondary	presence of cardiovascular risk factors	arterial hypertension yes vs. no, hyperlipidemia yes vs. no, smoking yes vs. no vs. former, diabetes mellitus yes vs. no, coronary artery disease yes vs. no	2 minutes; Baseline (recruiting time approx. 2 years) and follow-up (5 years after individual baseline)
Secondary	MDS-UPDRS (Movement Disorder Society Unified Parkinson's Disease Rating Scale) parts I-IV	rates clinical severity of parkinsonian symptoms, range 0-260 points with higher points meaning more severe symptoms	20-30 minutes; Baseline (recruiting time approx. 2 years) and follow-up (5 years after individual baseline)
Secondary	modified Essential Tremor Rating Assessment Scale (mTETRAS)	rates clinical severity of ET symptoms, ranging from 0-80 (the "modified" means the inclusion of 2 additional items rating rest tremor) with higher points meaning more severe motor symptoms; also includes a subscale rating activities of daily living ranging from 0-48 points with more points meaning more severe disability due to ET	10 minutes; Baseline (recruiting time approx. 2 years) and follow-up (5 years after individual baseline)
Secondary	Scale for the assessment and rating of ataxia (SARA)	assesses symptoms of ataxia, ranging from 0 (no ataxia) to 40 (most severe ataxia)	5-10 minutes; Baseline (recruiting time approx. 2 years) and follow-up (5 years after individual baseline)
Secondary	Verbal fluency animals (part of the CERAD-plus test battery)	patients needs to say as many animals as possible within 1 minute, the more, the better	1 minute; Baseline (recruiting time approx. 2 years) and follow-up (5 years after individual baseline)
Secondary	Boston Naming Test (part of the CERAD-plus test battery)	the patient needs to name 15 items (shown as pictures) correctly, the more, the better	2 minutes; Baseline (recruiting time approx. 2 years) and follow-up (5 years after individual baseline)
Secondary	Mini Mental State Examination Test (MMSE; part of the CERAD-plus test battery)	a cognitive screening test with a minimum of 0 and a maximum of 30 points	3-5 minutes; Baseline (recruiting time approx. 2 years) and follow-up (5 years after individual baseline)
Secondary	word list learning (part of the CERAD-plus test battery)	the patient is shown 10 words which he needs to remember and repeat immediately after reading them (within 90 seconds); there a three tries; the more he remembers, the better	10 minutes; Baseline (recruiting time approx. 2 years) and follow-up (5 years after individual baseline)
Secondary	constructive praxis (part of the CERAD-plus test battery)	the patient needs to draw 4 figures from a model which are then rated according to prespecified criteria (maximum of 11 points, the more the better)	20-30 minutes; Baseline (recruiting time approx. 2 years) and follow-up (5 years after individual baseline)
Secondary	word list recall (part of the CERAD-plus test battery)	the patient needs to remember as many of the 10 words learned in "word list learning"; time limit 90 seconds	90 seconds; Baseline (recruiting time approx. 2 years) and follow-up (5 years after individual baseline)
Secondary	word list recognition (part of the CERAD-plus test battery)	the patient needs decide whether a word shown to him was part of the 10 words learned before; there a 20 words in total, and 10 each were part of the learned words while 10 where not; the more he/she remembers correctly, the better (1 point for each correctly identified word)	2 minutes; Baseline (recruiting time approx. 2 years) and follow-up (5 years after individual baseline)
Secondary	constructive praxis recall (part of the CERAD-plus test battery)	the patients needs to draw the 4 figures from "constructive praxis" from memory; they are then rated according to the same criteria with a maximum of 11 points	3-4 minutes; Baseline (recruiting time approx. 2 years) and follow-up (5 years after individual baseline)
Secondary	Trail Making Test A (part of the CERAD-plus test battery)	the patient needs to connect numbers in ascending order from 1 to 25, time is measured in seconds (the faster, the better)	2 minutes; Baseline (recruiting time approx. 2 years) and follow-up (5 years after individual baseline)
Secondary	Trail Making Test B (part of the CERAD-plus test battery)	the patient needs to connect numbers and letters in ascending and alternating order from 1 to 13 and A to L, respectively, time is measured in seconds (the faster, the better)	2 minutes; Baseline (recruiting time approx. 2 years) and follow-up (5 years after individual baseline)
Secondary	s-words (part of the CERAD-plus test battery)	the patient needs to list as many words starting with the letter "s" within 60 seconds as possible; the more the better	1 minute; Baseline (recruiting time approx. 2 years) and follow-up (5 years after individual baseline)
Secondary	Frontal Assessment Battery (FAB)	a neuropsychological test focusing on executive function, ranging from 0 (most impaired) to 18 (normal)	5 - 10 minutes; Baseline (recruiting time approx. 2 years) and follow-up (5 years after individual baseline)
Secondary	Geriatric Depression Scale (GDS)	a short questionnaire rating depressive symptoms, ranging from 0 (no depressive symptoms) to 15 (most severe depressive symptoms)	3-5 minutes; Baseline (recruiting time approx. 2 years) and follow-up (5 years after individual baseline)
Secondary	Hospital Anxiety and Depression Scale (HADS)	a questionnaire rating anxiety and depressive symptoms, ranging from 0 (no depressive/anxious symptoms) to 42 (most severe symptoms)	5 minutes; Baseline (recruiting time approx. 2 years) and follow-up (5 years after individual baseline)
Secondary	Non-Motor Symptoms Scale for Parkinson's Disease (NMSS)	a questionnaire rating non motor symptoms, ranging from 0 (no symptoms) to 128 (most severe non motor symptoms)	5 minutes; Baseline (recruiting time approx. 2 years) and follow-up (5 years after individual baseline)
Secondary	RBD Screening Questionnaire	rates probability for the presence of RBD (REM sleep behavior disorder) using 13 questions; points are given from 0 to 13 with higher points indicating a higher probability for RBD	2 minutes; Baseline (recruiting time approx. 2 years) and follow-up (5 years after individual baseline)
Secondary	Global Physical Activity Questionnaire (GPAQ)	the GPAQ is a questionnaire provided by the WHO and rates the extent of physical (-in-) activity; rating is done according to the WHO manual available from the WHO website	5-7 minutes; Baseline (recruiting time approx. 2 years) and follow-up (5 years after individual baseline)
Secondary	Quality of Life in Essential Tremor Questionnaire (QUEST)	a questionnaire rating quality of life specifically in ET patients; ranging from 0 (best quality of life) to 120 points (worst quality of life)	5 minutes; Baseline (recruiting time approx. 2 years) and follow-up (5 years after individual baseline)
Secondary	University of Pennsylvania Smell Identification Test (UPSIT)	a smell test ranging from 0 (worst olfactory function) to 40 points (best olfactory function)	10-15 minutes; Baseline (recruiting time approx. 2 years) and follow-up (5 years after individual baseline)
Secondary	Montreal Cognitive Assessment (MOCA)	a screening cognitive test rating cognitive dysfunction from 0 (worst) to 30 (best)	5-10 minutes; Baseline (recruiting time approx. 2 years) and follow-up (5 years after individual baseline)
Secondary	Auditory verbal learning test	assesses how well patients can remember 15 words after hearing them; the more they can remember, the better	5 minutes; Baseline (recruiting time approx. 2 years) and follow-up (5 years after individual baseline)
Secondary	Symbol Digit Modalities Test (SDMT)	patients need to translate specific symbols into numbers (1-9) using a key; they more the can translate in 90 seconds, the better	90 seconds; Baseline (recruiting time approx. 2 years) and follow-up (5 years after individual baseline)
Secondary	Brief Visuospatial Memory Test	patients can look at 6 figures for 10 seconds each, then they have to reproduce them; 3 trials; the more they remember, the better	2-3 minutes; Baseline (recruiting time approx. 2 years) and follow-up (5 years after individual baseline)
Secondary	Comprehensive trail making test 4	patients have to connect numbers (1 to 21) in ascending order with lines; time is measured in seconds; the faster, the better	1-2 minutes; Baseline (recruiting time approx. 2 years) and follow-up (5 years after individual baseline)
Secondary	Comprehensive trail making test 5	patients have to connect numbers (1 to 13) and letters (A to L) in ascending order and alternatingly with lines; time is measured in seconds; the faster, the better	1-2 minutes; Baseline (recruiting time approx. 2 years) and follow-up (5 years after individual baseline)
Secondary	Regensburg word fluency test	patients have to list words starting with "g" or "r" alternatingly or things within the categories of "clothes" or "flowers" alternatingly; they have 1 minute for each of the two tasks, the more they can list, the better	2 minutes; Baseline (recruiting time approx. 2 years) and follow-up (5 years after individual baseline)
Secondary	EQ-5D	a quick questionnaire (5 questions) rating quality of life, ranging from 0 (very bad) to 1 (best)	1-2 minutes; Baseline (recruiting time approx. 2 years) and follow-up (5 years after individual baseline)
Secondary	resilience scale (RS-13)	a quick questionnaire rating resilience, ranging from 13 (least resilience) to 91 points (highest resilience)	1-2 minutes; Baseline (recruiting time approx. 2 years) and follow-up (5 years after individual baseline)
Secondary	Pittsburgh Sleep Quality Index (PSQI)	a quick questionnaire rating sleep quality, ranging from 0 (best sleep) to 21 points (worst sleep quality)	3-4 minutes; Baseline (recruiting time approx. 2 years) and follow-up (5 years after individual baseline)
Secondary	Digital Spiral Drawing	patients are asked to draw Archimedes spirals (a total of 4, 2 with each hand) on a standard tablet PC using a touchpen; the process is done using a free available website-based application (http://www.trsper.com/); the main outcome is visual rating of the spirals ranging from 0 (perfectly normal) to 9 (worst spiral)	2-3 minutes; Baseline (recruiting time approx. 2 years) and follow-up (5 years after individual baseline)
Secondary	Schellong Test	blood pressure test for orthostatic hypotension; blood pressure is measured non-invasively using a automatic device at the left arm in seating position and after 1 and 3 minutes of standing; orthostatic hypotension is defined as a drop in systolic blood pressure of 20mmHg or more and/or of diastolic blood pressure of 10mmHg or more	3.5 minutes; Baseline (recruiting time approx. 2 years) and follow-up (5 years after individual baseline)
Secondary	serum glial fibrillary acidic protein (sGFAP)	sGFAP-level is measured from serum using SIMOA-technology	5 minutes; Baseline (recruiting time approx. 2 years) and follow-up (5 years after individual baseline)
Secondary	serum neurofilament light (sNfL)	sNfL-level is measured from serum using SIMOA-technology	5 minutes; Baseline (recruiting time approx. 2 years) and follow-up (5 years after individual baseline)
Secondary	Transcranial sonography	the presence of hyperechogenicity (yes/no and area in cm2) of the substantia nigra is measured using transcranial sonography	10 minutes; Baseline (recruiting time approx. 2 years) and follow-up (5 years after individual baseline)
Secondary	tremor analysis	tremor frequency and total tremor power are measured	20 minutes; Baseline (recruiting time approx. 2 years) and follow-up (5 years after individual baseline)
Secondary	cerebral MRI	white matter hyperintensities (volume in mm3)	45 minutes; Baseline (recruiting time approx. 2 years) and follow-up (5 years after individual baseline)
Secondary	cerebral MRI	presence of lacunes (number of)	45 minutes; Baseline (recruiting time approx. 2 years) and follow-up (5 years after individual baseline)
Secondary	cerebral MRI	cerebral microbleeds (number of)	45 minutes; Baseline (recruiting time approx. 2 years) and follow-up (5 years after individual baseline)
Secondary	cerebral MRI	volumetry of total brain and regions (in mm3)	45 minutes; Baseline (recruiting time approx. 2 years) and follow-up (5 years after individual baseline)
Secondary	cerebral MRI	Diffusion tensor imaging parameters (fractional anisotropy, mean diffusivity, radial diffusivity)	45 minutes; Baseline (recruiting time approx. 2 years) and follow-up (5 years after individual baseline)
Secondary	cerebral MRI	nigrosome-1-imaging (presence of swallow tail sign yes vs. no)	45 minutes; Baseline (recruiting time approx. 2 years) and follow-up (5 years after individual baseline)
Secondary	optic coherence tomography (OCT)	thickness of retinal nerve fiber layer in both eyes and each quadrant and in vicinity of the macula and papilla	5-10 minutes; Baseline (recruiting time approx. 2 years) and follow-up (5 years after individual baseline)
Secondary	optic coherence tomography (OCT)	thickness of ganglion cell layer in both eyes and each quadrant and in vicinity of the macula and papilla	5-10 minutes; Baseline (recruiting time approx. 2 years) and follow-up (5 years after individual baseline)
Secondary	optic coherence tomography (OCT)	thickness of inner plexiform layer in both eyes and each quadrant and in vicinity of the macula and papilla	5-10 minutes; Baseline (recruiting time approx. 2 years) and follow-up (5 years after individual baseline)
Secondary	optic coherence tomography (OCT)	thickness of choroidea in both eyes and each quadrant and in vicinity of the macula and papilla	5-10 minutes; Baseline (recruiting time approx. 2 years) and follow-up (5 years after individual baseline)
Secondary	Olfactory mucosa swab	swab of the olfactory mucosa testing for alpha-synuclein using a seeding assay (outcome: presence of misfolded alpha-synuclein yes vs. no)	5-10 minutes; Baseline (recruiting time approx. 2 years) and follow-up (5 years after individual baseline)