The Use of the CUE1 in People With Parkinson's Disease and Related Disorders

Dystonia Clinical Trial

Official title: The Use of the CUE1 Device in People With Idiopathic Parkinson's Disease and Related Disorders: A Feasibility Study

Status Not yet recruiting

Clinical Trial Summary

People with Parkinson's disease (PD) commonly experience a range of both motor (e.g., bradykinesia, rigidity, tremor, and postural instability) and non-motor (e.g., fatigue, psychiatric and behavioural disturbances, autonomic dysfunction, cognitive impairment, sleep dysfunction and olfactory loss) features. Currently, it is challenging to alleviate these symptoms with first-line treatment, the medications such as levodopa. The CUE1 is a non-invasive device, which is approved for sale in the UK market as a Class I low risk device. It is worn on the sternum or other part of the body such as the forearm and attaches to the skin via an adhesive patch which has been dermatologically tested and approved.

The CUE1 delivers pulsing cueing and vibrotactile stimulation to help improve symptoms in people with PD and it has shown to be effective in doing so in previous small case studies. This 9-week feasibility study aims to investigate the feasibility, safety, tolerability and effect of using the CUE1 as an intervention to improve motor and non-motor symptoms in people with PD and related movement disorders. People with clinical diagnosis of idiopathic PD and related disorders including those with progressive supranuclear palsy, multiple system atrophy, corticobasal degeneration, and vascular Parkinsonism as well as atypical dystonias and tremor disorders aged over 18 years old who have the capacity to provide a written consent form to take part in the study, will receive as intervention to wear the CUE1 device at home, on daily basis while carrying out their activities of daily living. Participants will also have to attend four face-to-face appointments of approximately half a day, at weeks -0, -3, -6 and -9 of the study to discuss how they are getting on with using the CUE1 and complete questionnaires on their symptoms, walking, balance, and movement tests as well as a participant's clinical diary.

Clinical Trial Description

Background:

Cueing is a mechanism of applying an external temporal or spatial stimulus to facilitate movement initiation and continuation and it can be somatosensory, auditory, attentional or visual. It is reported to work by shifting habitual motor control to goal directed motor control. Many studies have demonstrated that cueing helps to improve postural control, balance, FOG, as well as DT performance in activities involving the upper and lower limbs in people with PD. However, many cueing modalities used for the research purposes in the laboratory environments cannot be easily replicated in people's homes. Thus, a recent narrative review recommends the development of cueing wearable systems that can be used at home or in the community to improve gait and posture in PD.

Interventions utilising vibrotactile sensory stimulation in PD can be split into two main groups: a) whole body vibrotactile stimulation and b) focused (e.g., targeted) vibrotactile stimulation. The results on the effectiveness of whole body vibrotactile stimulation on sensory dysfunction and motor symptoms are mixed with a large variation being reported from none to small improvement on motor symptoms, balance, gait and mobility. On the other side, focused vibrotactile stimulation which is a non-invasive neuromodulation technique used by somatosensory cues (e.g., tactile/somatosensory cueing) to apply gentle vibrations to focal joints in the body may have a more positive and consistent effect. Trials which include cylindrical vibration devices on the triceps, a vibrotactile waistband around the abdomen in FOG, vibrotactile insoles to reduce falls and a proprioceptive stabiliser on postural instability show promising results. The CUE1 is a non-invasive medical device which utilises a metronome-like pulsed vibration which represents both auditory and somatosensory low frequency cueing and high frequency focused vibrotactile stimulation to help improve motor task performance in people with PD. It is a CE marked and MHRA registered non-invasive medical device.

Rationale for the study:

Like other cueing and vibrotactile stimulation devices, the CUE1 stands out as a non-invasive medical instrument. It employs a metronome-like pulsed vibration, incorporating both auditory and somatosensory low-frequency cueing, along with high-frequency targeted vibrotactile stimulation. This design aims to enhance motor task performance in individuals with PD. Preliminary assessments of employing the CUE1 indicated an overall enhancement of 16.75% in motor symptoms, as evidenced in the White Paper on Proof of Concept from 2019. This improvement was observed not only in the MDS-UPDRS Part III Motor test score-considered the benchmark for evaluating motor symptoms in individuals with PD-but also in various assessments such as the TUG test, TTT, and diverse gait features. Moreover, users reported that donning the CUE1 device contributed to enhanced fatigue levels and increased subjective balance confidence.

Subsequent investigations from smaller-scale studies revealed notable advancements linked to CUE1 usage. Specifically, the device was shown to significantly boost gait speed in the TUG test and improve MDS-UPDRS performance scores while reducing falls by an impressive 85%. Furthermore, a reduction in Freezing of Gait (FOG) and an augmentation in walking speed, accompanied by positive feedback from individuals with PD regarding their experience with the CUE1 has been shown.

This single group feasibility study will test primarily the feasibility, safety and tolerability and secondary the effect of the CUE1 device in people with PD and related disorders. This clinical study aims to identify whether the results seen in the prototype testing and previous small studies can be reproduced in a controlled clinical setting. Overall the risk assessment related to the use of the CUE1 device has been previously tested on people with PD and has shown to have a minimal chance for error or adverse effect to the patient. Based on real world data, the CUE1 has shown to be effective in significantly improving motor symptoms such as rigidity, stiffness, tremor and slowness of movement in people with PD. CUE1 has also shown to improve fatigue, walking speed, balance and FOG and decrease falls in people with PD. The potential harm for the people with PD was very low, the acceptance of using the CUE1 device was very good, and positive user feedback was received. The device also utilised medical grade established silicone-based skin adhesives. The product is water resistant and designed to CE standards hence product and electrical malfunction risk will be low.

Positive results arising from this feasibility study will strengthen the evidence that the CUE1 device is feasible to be used, tolerated, safe and help to improve movement and mobility in people living with PD and related disorders. It may also assist in selecting the most appropriate outcome measures to test the effectiveness of the CUE1 and contribute to the growing academic interest in the application of peripheral stimulation in other neurological disorders with movement, gait and balance problems such as various types of dystonias and tremors, multiple sclerosis, stroke and vestibular disorders.

Methodology:

This is a 9-week feasibility study which will involve wearing the CUE1 device on a daily basis at participants' homes while they continue their usual activities of daily living (ADL). The CUE1 is a non-invasive medical device which delivers low frequency metronomes like tactile cueing and high frequency focused vibrotactile stimulation. All participants will be using the same pre-programmed settings for the CUE1 device which are: vibration strength delivered at 80%, pulse length 800 milliseconds (ms), and rest length 800ms as set at baseline and will not change. The CUE1 device is attached to the skin via an adhesive patch which has been dermatologically tested and approved. Participants will be provided with the adhesive patches and shown how to use them and the CUE1 device by the research team.

Intervention

All participants will use the CUE1 device as follows:

• during the first two weeks (e.g., 1-2 weeks) of the 9 weeks in the study: once a day for a continuous duration of 2 hours in the morning, 1 hour after taking the medication (if any) for PD or related disorder, every single day;

• during the weeks 4-5 of the 9 weeks in the study: once a day for a continuous duration of 8 hours, starting from morning, 1 hour after taking the medication (if any) for PD or related disorder, every single day;

• during the weeks 7-8 of the 9 weeks in the study: only at night, through all night, every single night and not during the day at all;

Participants have to wear the device only for the time they use it. They must then remove it but keep the adhesive on the skin until the next use of the device. They cannot keep the device on their body deactivated, until the next use.

Assessments Four face to face appointments will be arranged for each participant. The appointments will take place at week-0 (baseline), week-3 (follow up 1), -6 (follow up 2), and -9 (follow up 3). Each appointment will last approximately half a day.

These appointments will be used to complete the participant's eligibility (baseline appointment)/ re-assess the participant's eligibility (follow-up appointments) for taking part in the study, explain information related to the CUE1 device, physically observe any adverse reactions to CUE1 device, discuss and participant's response to the intervention, collect self-reported and objective data and answer any queries participants may have in relation to their symptoms and trial. During these appointments, the research team will help each participant to set up on their phone the reminders for when to wear and when not to wear the CUE1 device as well as when to complete the participant's clinical diary. The research team will physically observe participant's skin at the site where the adhesive patch was applied for any skin irritation, redness, and/or sensitivity. At the end of the trial, participants can keep the CUE1 device they used to continue long term usage if they find it beneficial. Those who do not wish to keep the CUE1 device, will be welcome to return it to the research team.

Research sites:

Participants' Identification Sites are Barts Health NHS, Neurology, E1 1BB and Brying Assessment and Rehabilitation Unit, Homerton University Hospital NHS Trust, E9 66SR. The recruitment site is Wolfson Institute of Population Health, Queen Mary University of London, EC1M 6BQ. The identification of Participants will be undertaken by Dr Viktoria Azoidou who is employed full time by QMUL but holds a research passport for Barts Health NHS. The recruitment will be undertaken by Dr Azoidou as well at the QMUL as all other research activities.

Objectives/aims:

The primary objective is to assess the feasibility, safety and tolerability of the CUE1 device as intervention in people with idiopathic PD and related disorders aged over 18 years old.

The secondary objective is to investigate the effect of the CUE1 device on participants' motor and non-motor symptoms, gait, balance and falls risk.

Statistical consideration:

As this is a single group feasibility study, there is no formal plan for formal statistical analysis due to the small sample size and lack of statistical power. However, for a future trial an analysis plan has been developed which will be run in this study to determine its appropriateness.

Sample size:

Sample size is followed as recommended from previous literature for pilot studies. The required sample size for this study is a minimum 10 people with no maximum limit to recruitment. Instead, we have a timed deadline for recruitment of the last participant which is the 31st of December 2024. This will allow the researchers to gain preliminary data on the primary outcomes of feasibility, safety and tolerability of the CUE1 intervention. This will also provide sufficient data to explore trends for effectiveness to allow for sample size estimates to be drawn up for a future trial. ;

Related Conditions & MeSH terms

• Corticobasal Degeneration
• Dystonia
• Multiple System Atrophy
• Parkinson Disease
• Parkinson's Disease and Parkinsonism
• Parkinsonian Disorders
• Progressive Supranuclear Palsy
• Shy-Drager Syndrome
• Supranuclear Palsy, Progressive
• Tremor
• Vascular Parkinsonism

• NCT number: NCT06174948
• Study type: Interventional
• Source: Queen Mary University of London
• Contact: Cristina Simonet, PhD
• Phone: 020 7882 3543
• Email: c.simonet@qmul.ac.uk
• Status: Not yet recruiting
• Phase: N/A
• Start date: March 2024
• Completion date: December 2025