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

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Dystonia; Multiple System Atrophy; Corticobasal Degeneration; Progressive Supranuclear Palsy; Tremor; Parkinson's Disease and Parkinsonism; Vascular Parkinsonism
• Intervention / Treatment: Device: CUE1 non-invasive device

Detailed 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.

• Study Type: Interventional
• Enrollment (Estimated): 10
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Cristina Simonet, PhD; Phone Number: 020 7882 3543; Email: c.simonet@qmul.ac.uk
• Study Contact Backup: Name: Viktoria Azoidou, PhD; Phone Number: 020 7882 3850; Email: v.azoidou@qmul.ac.uk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Adults over 18 years old
• Clinical diagnosis of idiopathic PD and related disorders including progressive supranuclear palsy (PSP), multiple system atrophy (MSA), corticobasal degeneration (CBD), and vascular Parkinsonism (VaP) as well as atypical dystonias and tremor disorders
• willing to participate and written consent provided after read the participant information sheet.

Exclusion Criteria:

Individuals with:

• other neurological disorders excluding idiopathic PD, related disorders such PSP, MSA, CBD, and VaP as well as atypical dystonias and tremor disorders, affecting movement, balance and gait
• metabolic or autoimmune disorders affecting movement, balance and gait
• acute orthopaedic disorders influencing balance control and gait
• audiovestibular disorders including severe hearing loss
• visual disturbances, poor eyesight
• not able to provide written consent form to participate
• clinical diagnosis of cognitive impairment including dementia or Alzheimer's.
• Mental impairments (illusions, hallucinations, impulse control disorders) (self-reported)

Technical contraindications related to CUE1 device:

• implanted metallic or electronic devices usage
• hypersensitivity to vibrotactile stimulation
• skin conditions and/or open wound in the area of where the device will be positioned (e.g., sternum) if taking medicines for PD or related disorder, then on stable dose of treatment for the last three months.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: people with Parkinson's disease and related disorders; 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; 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.

Device: CUE1 non-invasive device; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recruitment rate	This is a feasibility outcome, the recruitment rate which will be calculated as the percentage of eligible participants enrolled in the study. This will be reported at each follow up appointment at weeks -3, -6 and -9.	1 minute
Compliance with interventions	This is a feasibility outcome, compliance with interventions, which will be reported as the percentage of days completed using the CUE1 device and duration of using the CUE1 device. These will be reported at each follow up appointment at weeks -3, -6 and -9.	1 minute
Dropout rate	This is a feasibility outcome which will report the dropout rate at each follow up appointment at weeks -3, -6 and -9.	1 minute
Physical observation	This is a safety and tolerability outcome which will be assessed by carrying out a physical observation by research team during the face to face appointments of any adverse event occurring as a result of using the adhesive patches. The adverse events in relation to the CUE1 device will be reported in the participants' clinical diary and discussed during the appointments with the research team.	1 minute

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patient's Global Impression of Change (PGI-C) questionnaire	There are two parts in the PGI-C questionnaire. In part one, the patient scores on a scale 0-7 (0 = no change or condition has got worse, 7 = a great deal better, and a considerable improvement that has made all the difference) the change in their activity limitations, symptoms, emotions and overall QoL related to painful conditions. In part two, the patient scores on a scale 0-10 (0 = much better, 10 = much worse), the score that matches their degree of change since beginning the specific care (here the intervention with CUE1). The PGI-C will be completed at follow up appointments, at weeks-3, -6, and -9.	5 minutes
Participant's clinical diary	This will be completed daily by the participant at home for 9 weeks, starting from week-1 of and finishing at the end of week-9 of the intervention. The diaries will be completed on the weeks of the intervention (e.g., 1-2, 4-5 and 7-8). The research team will provide the same instructions on how to complete the participant's diary to each person during the baseline appointment at week-0.	15 minutes
Functional Gait Assessment (FGA)	The FGA is a 10-item test that assesses performance on complex gait tasks (i.e., walking with head turns, stepping over an obstacle, stopping and turning or climbing stairs). Scores for each item are between 0-3. The highest score is 30 and greater outcomes are indicative of better performance. The FGA has been validated in healthy people, older adults with a history of falls and balance impairments, and people with balance problems including those with PD. The minimal detectable change for the FGA is reported to be 4 points in people with PD. Scores ≤22/30 identify fall risk and are predictable of falls in community-living older persons within 6 months. In people with PD, the cutoff point for predicting falls is 18/30, with sensitivity of 80.6%, specificity of 80.0%, and positive likelihood ratio of 4.03.	10 minutes
Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Motor Part III	The MDS-UPDRS Motor Part III assesses the motor symptoms in people with PD. There are 33 scores based on 18 questions with several right, left or other body distribution scores. All items have 5 response options with uniform anchors of 0 = normal, 1 = slight (symptoms/signs with sufficiently low frequency or intensity to cause no impact on function), 2 = mild (symptoms/signs of frequency or intensity sufficient to cause a modest impact on function), 3 = moderate (symptoms/signs sufficiently frequent or intense to impact considerably, but not prevent function), and 4 = severe (symptoms/signs that prevent function). Higher scores indicate greater impact of PD symptoms. Score range between 0 and 132, 32 and below is mild, 59 and above is severe.	10 minutes
Timed Up and Go test (TUG)	The TUG assesses mobility, balance, walking ability, and fall risks. The mean time in people with PD has been reported between 10.3-14.8 seconds.	5 minutes
Bradykinesia Akinesia Incoordination test (BRAIN test)	The BRAIN test is used to assess upper limb motor function. The BRAIN test has been redeveloped to run in all internet browser software and has been validated in patients with PD and controls. Participants use the index finger of a single hand to alternately strike the 'S' and ';' keys on a standard computer keyboard, as fast and accurately as possible. The test is repeated for the other hand. The BRAIN test can be accessed at http://www.predictpd.com/braintest and applications to use this can be directed to AJN via the same web link.	5 minutes
Distal Finger Tapping (DFT)	The DFT test is a web-based keyboard tapping test which has been validated to remotely evaluate upper limb movements and quantify separate kinetic components such as speed, akinesia and rhythm as part of motor dysfunction in PD. It is available online via https://predictpd.com/en/braintest, and compatible with regular laptops and computers with a keyboard. The DFT test consists of a 20-second single key tapping test. Participants will be instructed to repeatedly tap the down arrow key with their left index finger, as fast as possible for 20 s, whilst simultaneously depressing the left arrow key with their left middle finger. The same task will then be repeated for the right hand. These instructions stabilise the wrist and forearm, isolating movement to the index finger metacarpal joint, thereby giving a true measurement of distal finger movement.	5 minutes
Activity-specific Balance Confidence (ABC)	The ABC is a 16-item questionnaire which assesses self-perceived balance confidence in daily activities. Scores range from 0-100; scores ≤ 67/100 are associated with increased fall risk. Higher scores indicate greater balance confidence.	5 minutes
Pittsburgh Sleep Quality Index (PSQI)	The PSQI includes seven component scores: subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbance, use of sleeping medication, and daytime dysfunction. Scores range from 0-21 with a higher total score indicating worse sleep quality. In distinguishing good and poor sleepers, a global PSQI score > 5 yields sensitivity of 89.6% and specificity of 86.5%.	5 minutes
Fatigue Severity Scale (FSS)	The FSS is a 9-item scale which measures the severity of fatigue and its effect on a person's activities and lifestyle in patients with a variety of disorders, including those with PD diagnosis. The items are scored on a 7-point scale with 1 = strongly disagree and 7= strongly agree. The minimum score = 9 and maximum score possible = 63. Higher the score = greater fatigue severity.	5 minutes
Parkinson's Disease Questionnaire (PDQ-39)	The PDQ-39 is a 39-item self-report questionnaire, which assesses PD-specific health related quality over the last month. It assesses how often patients experience difficulties across the 8 quality of life dimensions and impact of PD on specific dimensions of functioning and well-being. The scoring is done on a 5-point ordinal system (e.g., 0 = never, 1 = occasionally, 2 = sometimes, 3 = often, 4 = always). Each dimension's total score ranges from 0 (never have difficulty) to 100 (always have difficulty). Lower scores reflect better quality of life.	5 minutes
Movement Disorder Society-Non-Motor Scale (MDS-NMS)	The MDS-NMS is a revision of the Non-Motor Symptoms Scale (NMSS) and was developed to improve and refine the assessment of non-motor symptoms in people with PD. This rater-completed assessment measures frequency and severity of 13 non-motor domains, over 52 items and covers a range of key non-motor symptoms both PD and treatment related, and in greater depth, compared with the NMSS. The scale also has a new MDS-NMS Non-Motor Fluctuations (NMF) Subscale to assess changes in non-motor symptoms in relation to the timing of anti-parkinsonian medications across 8 domains. The scoring is done on a scale 0-4 for frequency/duration and severity of symptoms (e.g., 0 absence to 4 most severe/frequent). Total score ranges between o-334, the greater the score, the more severe and frequent the non-motor symptoms experienced.	5 minutes
Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) (Parts I, II, IV).	The rest of the MDS-UPDRS scale consists of three parts (apart from Part III Motor which will be completed already above): Part I, II and IV which include questions to assess non-motor experiences of daily living, motor experiences of daily living, and motor complications, of people living with PD, respectively.	15 minutes
Participant's satisfaction form	This form will be will be provided to participants to complete at the last follow up appointment (week -9) to feedback on their experience on using the intervention, and support and services received from the research team.	5 minutes

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Age	Age is recorded in years and collected as baseline demographic characteristic only.	within 1 minute
Gender	Gender is recorded as male, female, and other, and collected as baseline demographic characteristic only.	within 1 minute
Disease duration	The disease duration is recorded in years and collected as baseline demographic characteristic only.	within 1 minute
Hoehn & Yahr (H &Y)	Hoehn & Yahr (H & Y) scale is used to record the disease severity for people with Parkinson's disease.	within 1 minute
Montreal Cognitive Assessment (MoCA) tool	The MoCA is a rapid screening tool for mild cognitive impairment. It assesses different cognitive domains: attention and concentration, executive function, memory, language, visuoconstructional skills, conceptual thinking, calculations, and orientation. It has been recommended that cut-off scores of <26/30 be used to identify multi-domain cognitive impairment.	within 5 minutes
Cognitive Behavioural Symptom Questionnaire (CBSQ)	The CBSQ is a measure of subjects' cognitive (i.e. beliefs) and behavioural responses to symptoms of their health condition. This measure includes five cognitive (i.e. beliefs) subscales: Symptom Focusing, Catastrophizing, Damaging Beliefs, Fear Avoidance and Embarrassment Avoidance; and two behavioural subscales: All or- Nothing and Avoidance/Rest. All items are rated on a 5-point Likert scale ranging from 'strongly disagree' to 'strongly agree'.	within 5 minutes
Illness Perception Questionnaire-Revised (IPQ-R)	The IPQ-R was used to measure participants' illness perceptions. The IPQ-R measures the key components in Leventhal's common sense self-regulatory model: Illness identity was measured by asking patients to indicate whether they have experienced and attribute a number of potential symptoms to their dizziness condition, with higher scores (range 0-24) indicating increased illness identity. In accordance with the recommendations from the authors, some items were added based on feedback from a patient-public involvement group so as to reflect the symptoms experienced by people with vestibular disorders. Causal Factors were measured by asking participants to list up to three things that they believed caused their condition.	within 5 minutes

Collaborators and Investigators

• Sponsor: Queen Mary University of London
• Investigators: Study Director: Alastair Noyce, PhD, Queen Mary University of London

Publications and helpful links

General Publications

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Study record dates

Study Major Dates

• Study Start (Estimated): March 1, 2024
• Primary Completion (Estimated): December 1, 2024
• Study Completion (Estimated): December 1, 2025

Study Registration Dates

• First Submitted: November 30, 2023
• First Submitted That Met QC Criteria: December 8, 2023
• First Posted (Actual): December 18, 2023

Study Record Updates

• Last Update Posted (Actual): February 20, 2024
• Last Update Submitted That Met QC Criteria: February 16, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: CUE1, Parkinson's disease, movement disorders
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Eye Diseases; Neurologic Manifestations; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Dyskinesias; Tauopathies; Cranial Nerve Diseases; Autonomic Nervous System Diseases; Ocular Motility Disorders; Paralysis; Primary Dysautonomias; Hypotension; Ophthalmoplegia; Parkinson Disease; Dystonia; Multiple System Atrophy; Shy-Drager Syndrome; Parkinsonian Disorders; Supranuclear Palsy, Progressive; Corticobasal Degeneration
• Other Study ID Numbers: 333484

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No