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Trial registered on ANZCTR


Registration number
ACTRN12618000819224
Ethics application status
Approved
Date submitted
9/05/2018
Date registered
14/05/2018
Date last updated
14/05/2018
Type of registration
Retrospectively registered

Titles & IDs
Public title
Effects of mechanical vibration on tremor in Essential Tremor patients
Scientific title
Assessment of tremor evolution in 18 Essential Tremor patients when mechanical afferent stimulation is applied.
Secondary ID [1] 294843 0
Nil known
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Essential Tremor 307790 0
Condition category
Condition code
Neurological 306836 306836 0 0
Other neurological disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
- Brief name.
Effects of mechanical afferent stimulation on tremor in Essential Tremor patients

- Materials.
In order to apply mechanical afferent stimuli and assess the ongoing tremor in patients, a device was designed and built which is able to deliver vibratory stimuli with different frequencies to the forearm and the hand and simultaneously record the movement of the wrist. Vibratory stimuli were delivered using piezoelectric actuators (model QP-10W, for the fingertips; PPA-4011 for the hand; PPA-1022 for the forearm; all from Mide Technology, US), which were controlled at 5 kHz through piezoelectric haptic drivers (DRV8662, Texas Instruments, US) via a data acquisition card (DAQ) (NI USB 6003, National Instrument, US) connected to a consumer laptop. The amplitude of the mechanical vibration was left constant during the experiment, and set to the maximum. Wrist movement was monitored at 100 Hz using inertial sensors (TechMCS, Technaid, SP).

- Procedures
The experiments are performed in the arm most affected by tremor, which is identified by a neurologist at the beginning of the experimental session. During the experiments, patients are comfortably seated in front of a desk. Piezoelectric actuators were located over the fingertips, the hand and the forearm, the areas where Pacinian corpuscle density is higher (Bruce Goldstein, 2010). To measure wrist movement, inertial sensors are strapped to the dorsal side of the hand and forearm. Patients perform a standard postural task, while their proximal arm rests on a purposely-built support which not constrain hand or forearm movements. The support decreases muscle fatigue and ensures repeatability across trials. During the trials, patients are instructed to hold the arm, forearm and hand outstretched against gravity, to trigger their tremor.
The experimental protocol consists of four 4-min trials in which different stimulation strategies are applied. These trials are interleaved with 10 min long resting periods. The experimental session lasts for ~90 minutes.
1. Stimulation at 50 Hz: vibration was delivered at 50 Hz, a frequency which should minimally recruit Pacinian corpuscles.
2. Stimulation at 250 Hz stimulation: vibration was delivered at 250 Hz, a frequency which should maximally recruit Pacinian corpuscles.
3. Increasing stimulation frequency: vibration was delivered in 50 Hz steps (increasingly, from 50Hz to 450Hz); each frequency was applied during 13.33 s. This trial was designed to test the frequency-dependency of the stimulation.
4. Random stimulation frequency: vibration was delivered at the same frequencies as during the IncreasingFreq trials, but their order was randomized; each frequency was again applied during 13.33 seconds. This trial was designed any potential adaptation to the stimulation from the frequency-dependent effects.
These trials are divided into four 60 s epochs: during the first epoch (Pre-stim) the patient’s basal tremor is assessed; during epochs 2 and 3 (Stim1 and Stim2), we apply vibratory stimuli as defined by the corresponding strategy; during the last epoch (Post-stim), the tremor is assessed to detect potential after-effects.

- Intervention providers
A neurologist and an engineer are present during the trials. The first is responsible of assessing the basal tremor of the patient and evaluating his/her state while the stimulation is applied. The engineer is responsible of managing the device and recording the data.
Both researchers monitor fidelity to the intervention by direct supervision.

- Modes of delivery
The protocol is provided to one participant at a time. Each patient completes the protocol once.

- Location
Hospital Universitario 12 de Octubre (Madrid, Spain)

- Tailoring and modifications
The protocol remains unaltered across applications. The only adaptation to patients is the choice of the arm most affected by tremor.
Intervention code [1] 301156 0
Treatment: Devices
Comparator / control treatment
The patients act as their own control. The amplitude of the basal tremor is assessed during 240 seconds, 10 minutes prior to trial 1. In addition, previously to each application of afferent stimulation, 60 seconds of the ongoing tremor is also measured.
Control group
Active

Outcomes
Primary outcome [1] 305832 0
Tremor amplitude is measured using Inertial Sensors (sample frequency of 100Hz).
Timepoint [1] 305832 0
This outcome is assessed continuously throughout the 4-min that each trial lasts.
Secondary outcome [1] 346695 0
No secondary outcomes are measured
Timepoint [1] 346695 0
Not applicable

Eligibility
Key inclusion criteria
Patients that had been diagnosed as having Essential Tremor
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1) Having a pacemaker implanted
2) Having a deep brain stimulator implanted
3) Previous history of epilepsy
4) Head trauma
5) Stroke

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Who is / are masked / blinded?



Intervention assignment
Crossover
Other design features
Phase
Type of endpoint/s
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
1/04/2014
Date of last participant enrolment
Anticipated
Actual
1/06/2017
Date of last data collection
Anticipated
Actual
30/06/2017
Sample size
Target
20
Accrual to date
Final
18
Recruitment outside Australia
Country [1] 10389 0
Spain
State/province [1] 10389 0
Madrid

Funding & Sponsors
Funding source category [1] 299440 0
Government body
Name [1] 299440 0
Spanish Ministry of Economy, Industry and Competitiveness
Country [1] 299440 0
Spain
Primary sponsor type
Government body
Name
Centre for Automation and Robotics, Spanish National Research Council
Address
Ctra. M300 Campo Real, Km 0,200
Arganda del Rey - 28500 Madrid
Country
Spain
Secondary sponsor category [1] 298730 0
Hospital
Name [1] 298730 0
University Hospital 12 de Octubre
Address [1] 298730 0
Avda. de Córdoba, s/n. 28041. Madrid
Country [1] 298730 0
Spain

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 300338 0
Local Ethical Committee of the “Hospital Universitario 12 de Octubre”
Ethics committee address [1] 300338 0
Avda. de Córdoba, s/n. 28041. Madrid
Ethics committee country [1] 300338 0
Spain
Date submitted for ethics approval [1] 300338 0
Approval date [1] 300338 0
25/02/2014
Ethics approval number [1] 300338 0
NºCEIC: 14/041

Summary
Brief summary
Background and study aims
Essential tremor (ET) is one of the most prevalent movement disorders in adults, affecting approximately 5% of people over age 65. ET manifests as a bilateral, largely symmetric postural or kinetic tremor involving the hands and forearms, and is often accompanied by head tremor. Importantly, even though as many as 75% of ET patients report significant disability, tremor is only effectively managed in 50% of all patients. Therefore, there is an important need to develop new treatments for ET.
Tremor in ET is thought to originate because of the projection of pathological oscillations in cerebello-thalamo-cortical pathways to the motoneurons innervating the affected muscles (Helmich et al., 2013), although its exact mechanisms remain elusive. A classic hypothesis proposes that the inferior olivary nucleus is the ultimate cause of tremor in ET, due to abnormal oscillations in the olivo-cerebellar pathways that are transmitted to thalamo-cortical circuits(Deuschl and Elble, 2000).
Mechanoreceptors, including Pacinian and Meissner corpuscles, are sensitive to vibratory stimuli. Sensory responses from both types of receptors are projected to the ipsilateral cuneate nucleus(Douglas et al., 1978), which has important projections to the thalamus and the inferior olivary nucleus (Douglas et al., 1978; Geborek et al., 2012), and therefore may provide a pathway to modulate the circuits that mediate tremor in ET. For example, direct stimulation of the cuneate nucleus has inhibitory effects on cerebellar activity in decerebrated cats(Geborek et al., 2012).
Our hypothesis is that vibration would recruit Pacinian corpuscles and thus modulate the abnormal activity in tremor-related pathways, which would in turn reduce the tremor.

Who can participate?
Patients aged over 18, males and females, who have been diagnosed as having Essential Tremor.

What does the study involve?
All the participants complete five 4-min trials. During the first, we measure the tremor amplitude without stimulating the patients. Trials 2-5 comprised a 1-min epoch during which we do not apply any stimulation, followed by a 2-min epoch in which we apply different kinds of stimulation strategies, which vary in the frequency of the vibration applied; trials end with a 1-min epoch in which we only measure the evolution of the tremor.

What are the possible benefits and risks of participating?
Participants may reduce their tremor amplitude when we apply the vibratory stimulation. There is no side effects of the experiment.

Where is the study run from?
Hospital Universitario 12 de Octubre (Madrid, Spain)

When is the study starting and how long is it expected to run for?
February 2016 to June 2017

Who is funding the study?
Ministry of Economy and Competitiveness (Spain)

Who is the main contact?
Dr Eduardo Racon
[email protected]
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 83346 0
Dr Eduardo Rocon
Address 83346 0
Centre for Automation and Robotics.
Ctra. Campo Real Km 0,2. 28500.
Arganda del Rey. Madrid.
Country 83346 0
Spain
Phone 83346 0
+34 91 8711900
Fax 83346 0
Email 83346 0
[email protected]
Contact person for public queries
Name 83347 0
Eduardo Rocon
Address 83347 0
Centre for Automation and Robotics.
Ctra. Campo Real Km 0,2. 28500.
Arganda del Rey. Madrid.
Country 83347 0
Spain
Phone 83347 0
+34 91 8711900
Fax 83347 0
Email 83347 0
[email protected]
Contact person for scientific queries
Name 83348 0
Julio Lora
Address 83348 0
Centre for Automation and Robotics.
Ctra. Campo Real Km 0,2. 28500.
Arganda del Rey. Madrid.
Country 83348 0
Spain
Phone 83348 0
+34 91 8711900
Fax 83348 0
Email 83348 0
[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

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