Combining VNS With PT Interventions for Individuals With PD

Combining Trans-auricular Vagus Nerve Stimulation With Physical Therapy Interventions for Individuals With Parkinson's Disease

Status

Completed

Phases

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT05871151

Acronym

VNS-PT-PD

Enrollment

Registered

2023-05-23

Start date

2023-10-01

Completion date

2024-12-01

Last updated

2025-12-17

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Parkinson Disease

Keywords

Parkinson's Disease, Exercise, Vagus Nerve Stimulation, VNS, taVNS

Brief summary

The purpose of this study is to evaluate the combined effects of non-invasive neuromodulation (specifically transauricular Vagus Nerve Stimulation) with exercise interventions to improve physical function and quality of life in individuals with Parkinsons Disease.

Detailed description

During this clinical trial, participants will be randomized into two groups, with half of the participants assigned to GROUP 1: active taVNS + exercise, and half of the participants assigned to GROUP 2: sham taVNS + exercise. The active taVNS + exercise group will receive 15 minutes of active taVNS prior to treatment. Participants who are randomized into the sham taVNS + exercise group will receive 0 mA of current for 15 minutes prior to treatment. All participants will be guided through exercises by a licensed physical therapist, which will include: 1) intensive exercises that focus on increasing the size and amplitude of movements; 2) task-specific practice, which involves practicing functional tasks, such as dressing, bathing, and cooking, in order to transfer the gains made in therapy to real-life situations. The exercise intervention proposed involves the supervision of a licensed PT at all times during the treatment session. Exercise will be provided in a clinical setting, 45 minutes per session, up to 3 sessions/week, for 4-6 weeks total.

Interventions

DEVICEtaVNS

Trans-auricular Vagus Nerve Stimulation is a non-invasive method of stimulating the auricular branch of the vagus nerve through the inner ear. Trans-auricular Vagus Nerve Stimulation will be provided using a commercially available device. The investigators will use custom earbuds that will make the experience significantly more comfortable than traditional transauricular Vagus Nerve Stimulation.

BEHAVIORALExercise

All participants will be guided through exercises led by a trained exercise specialist, and will include: 1) intensive exercises that focus on increasing the size and amplitude of movements; 2) task-specific practice, which involves practicing functional tasks, such as dressing, bathing, and cooking, in order to transfer the gains made in therapy to real-life situations. The exercise intervention proposed involves the supervision of a licensed PT at all times during the treatment session. Exercise will be provided in a clinical setting, 45 minutes per session, up to 3 sessions/week, for 4-6 weeks total.

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

SINGLE (Subject)

Masking description

Participants will receive either active or sham taVNS + exercise, but they will not be aware of whether they are receiving the active treatment or the sham treatment.

Intervention model description

Randomized Controlled Trial with two parallel groups

Eligibility

Sex/Gender

ALL

Age

35 Years to 80 Years

Healthy volunteers

Inclusion criteria

* Diagnosis of PD by a board-certified neurologist * age between 35 and 80 years * no walking aids * stable medication 4 weeks prior to and during the study * no falls in the past 6 months * participant must have MD who is willing to provide oversight and approval for clinically defined OFF state

Exclusion criteria

* mild cognitive impairment (MoCA <25) * self reported depression * antidepressive or antipsychotic medication * participation in a VNS study in the past year * disabling bradykinesia to ensure patients are able to participate in intensive physiotherapy (based on clinical impression and in accordance to UPDRS part III item 14 - to be administered in clinic) * prior history of cardiovascular, neurological or musculoskeletal disorders known to interfere with testing PD features * implanted medical device of any type * history of seizures * peripheral neuropathy including temporal mandibular disorders and Bells Palsy, and * vasovagal syncope.

Design outcomes

Primary

Measure	Time frame	Description
Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III	Baseline, immediately post-treatment (after 12 study visits, around 4-6 weeks), and at follow-up (4 weeks after last treatment)	In our study, we will utilize the Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III. This scale, widely used in the clinical and research settings, helps us evaluate the motor symptoms of Parkinson's Disease. The MDS-UPDRS Part III scale ranges from 0 to 132, with 0 representing no motor symptoms and 132 representing severe motor symptoms. Therefore, a higher score on the MDS-UPDRS Part III scale indicates a worse outcome, reflecting more severe motor symptoms associated with Parkinson's disease.
Six Minute Walk Test (6MWT)	Baseline, immediately post-treatment (after 12 study visits, around 4-6 weeks), and at follow-up (4 weeks after last treatment)	6-Minute Walk Test (6MWT): We utilize the 6-Minute Walk Test in our study to evaluate the functional exercise capacity of our participants. The 6MWT involves participants walking as far as they can in a span of six minutes on a flat, hard surface. The total distance covered in six minutes is recorded as the score. In this test, a greater distance indicates better physical endurance and mobility. Therefore, in our study, a higher score (greater distance walked) on the 6MWT represents a better outcome, signifying superior functional exercise capacity.
Ten Meter Walk Test (10MWT)	Baseline, immediately post-treatment (after 12 study visits, around 4-6 weeks), and at follow-up (4 weeks after last treatment)	The 10MWT is a timed walking test commonly used in clinical and research settings to assess an individual's gait speed and functional mobility. It measures the time it takes for a person to walk a distance of 10 meters (approximately 33 feet). The scale title, in this case, is the time in seconds required to complete the 10-meter walk. There are no specific minimum and maximum values for this measure since it depends on the individual's walking ability. However, lower scores (i.e., shorter times) generally indicate better outcomes, as they reflect faster gait speed and improved mobility. Conversely, higher scores (longer times) would suggest slower walking speed and potentially poorer functional mobility.
Mini-Best Test	Baseline, immediately post-treatment (after 12 study visits, around 4-6 weeks), and at follow-up (4 weeks after last treatment)	The Mini-Balance Evaluation Systems Test (Mini-BESTest) is a clinical assessment tool used to evaluate a person's balance and stability. It consists of 14 items that assess different aspects of balance, including anticipatory postural adjustments, reactive postural control, sensory orientation, dynamic gait, and stability during functional tasks. The scale title for the Mini-BESTest is the total score, which ranges from 0 to 28. Higher scores on the Mini-BESTest indicate better balance performance and greater overall stability. A score of 28 represents the best possible outcome, indicating excellent balance abilities across all assessed domains. Conversely, lower scores indicate poorer balance control and increased risk of falls.
Functional Gait Assessment (FGA)	Baseline, immediately post-treatment (after 12 study visits, around 4-6 weeks), and at follow-up (4 weeks after last treatment)	The Functional Gait Assessment (FGA) is a clinical measure used to assess an individual's walking ability and functional mobility. It evaluates various aspects of gait, including balance, coordination, range of motion, and adaptability. The FGA consists of 10 different tasks or conditions that challenge the person's walking abilities in different ways, such as walking while turning, walking over obstacles, or walking with eyes closed. The scale title for the FGA is the total score, which ranges from 0 to 30. Higher scores on the FGA indicate better functional gait performance and greater walking independence. A score of 30 represents the best possible outcome, reflecting excellent gait function across all assessed conditions. Conversely, lower scores suggest impaired gait function and reduced functional mobility.
mCTSIB	Baseline, immediately post-treatment (after 12 study visits, around 4-6 weeks), and at follow-up (4 weeks after last treatment)	The modified Clinical Test of Sensory Interaction on Balance (mCTSIB) is a diagnostic tool used to evaluate an individual's sensory integration and balance control. It assesses the person's ability to maintain balance under various sensory conditions. The mCTSIB involves four different standing positions, each with different sensory inputs: (1) feet together on a firm surface with eyes open, (2) feet together on a firm surface with eyes closed, (3) feet together on a foam surface with eyes open, and (4) feet together on a foam surface with eyes closed. The results presented in this section reflect the participant's composite mCTSIB score as measured by the BTrack Balance System. Composite scores range from 0 to 400. Higher scores indicate better balance control and greater sensory integration.

Secondary

Measure	Time frame	Description
Digit Symbol Substitution Test	Baseline, immediately post-treatment (after 12 study visits, around 4-6 weeks), and at follow-up (4 weeks after last treatment)	The DSST is a test of psychomotor and cognitive functions, including speed of processing, attention, memory, and manual dexterity. The test requires participants to substitute symbols for numbers based on a key, filling in as many blanks as possible within 90 seconds. Scores range from 0-90, and higher scores indicate better function.
Flanker	Baseline, immediately post-treatment (after 12 study visits, around 4-6 weeks), and at follow-up (4 weeks after last treatment)	The Flanker Inhibitory Control and Attention Test is an NIH Toolbox cognitive assessment of inhibitory control and attention. Participants respond to a central stimulus while ignoring flanking stimuli. Raw performance is based on accuracy across congruent and incongruent trials and, for participants with accuracy greater than 80 percent, reaction time is incorporated into the score. Accuracy and reaction time are each converted to a 0-5 subscore using NIH Toolbox scoring algorithms, and these subscores are summed to create a total raw score. This raw score is then converted to an age-adjusted scale score using nationally representative normative data. In this scoring system, a value of 100 represents the population mean for individuals of the same age, with a standard deviation of 15. Higher age-adjusted scale scores indicate better inhibitory control and attention, whereas lower scores represent poorer performance. Scale scores below approximately 85 (one standard deviation below th
MoCA	Baseline, immediately post-treatment (after 12 study visits, around 4-6 weeks), and at follow-up (4 weeks after last treatment)	The Montreal Cognitive Assessment (MoCA) is a widely accepted tool in both clinical and research settings, allowing us to evaluate cognitive abilities, specifically focusing on attention and concentration, executive functions, memory, language, visuoconstructional skills, conceptual thinking, calculations, and orientation. The MoCA scale ranges from 0 to 30, with a score of 30 indicating the highest level of cognitive function. Lower scores on the MoCA suggest a higher level of cognitive impairment. Therefore, in the context of our study, a higher score on the MoCA represents a better outcome, signifying superior cognitive performance.
SF-36	Baseline, immediately post-treatment (after 12 study visits, around 4-6 weeks), and at follow-up (4 weeks after last treatment)	The SF-36 is a self-reported questionnaire measuring health-related quality of life. It assesses dimensions like physical functioning, role limitations, pain, general health, vitality, social functioning, and mental health. It provides scores for each dimension and summary scores (PCS and MCS) for overall physical and mental health. Scale titles reflect specific dimensions. Scores range from 0 to 100, with higher scores indicating better health-related quality of life. SF-36 offers a comprehensive assessment of perceived health status and well-being.
Promise Neuro-QOL (Ability)	Baseline, immediately post-treatment (after 12 study visits, around 4-6 weeks), and at follow-up (4 weeks after last treatment)	The Patient Reported Outcomes Measurement Information System (PROMIS) Quality of Life in Neurological Disorders (Neuro-QoL) system assesses health-related quality of life in individuals with neurological conditions. The Neuro-QoL Ability to Participate in Social Roles and Activities scale evaluates a participant's self-reported ability to perform and engage in day-to-day activities. Scores are reported as T-scores, where 50 represents the population mean and 10 represents one standard deviation. Higher T-scores on this scale indicate better perceived ability and therefore reflect a more favorable outcome. Lower T-scores represent worse perceived ability. Clinically meaningful thresholds may include T-scores below approximately 40 (one standard deviation below the mean), which may indicate notably reduced ability to participate in daily activities.
DKEFS Color Word Interference Test - Condition One	Baseline, immediately post-treatment (after 12 study visits, around 4-6 weeks), and at follow-up (4 weeks after last treatment)	Delis-Kaplan Executive Function System (D-KEFS) Color Word Interference Test is used to assess cognitive flexibility and inhibitory control. Condition 1 is basic naming of color patches. All D-KEFS raw scores are converted to scaled scores, with a mean of 10 and a standard deviation of 3, corrected for each of the following 16 age-groups:8, 9, 10, 11, 12, 13, 14, 15, 16-19, 20-29, 30-39, 40-49, 50-59, 60-69, 70-79, and 80-89. Higher scores indicate better performance.
DKEFS Color Word Interference Test - Condition Two	Baseline, immediately post-treatment (after 12 study visits, around 4-6 weeks), and at follow-up (4 weeks after last treatment)	Delis-Kaplan Executive Function System (D-KEFS) Color Word Interference Test is used to assess cognitive flexibility and inhibitory control. Condition 2 is basic reading of color-words printed in black ink. All D-KEFS raw scores are converted to scaled scores, with a mean of 10 and a standard deviation of 3, corrected for each of the following 16 age-groups:8, 9, 10, 11, 12, 13, 14, 15, 16-19, 20-29, 30-39, 40-49, 50-59, 60-69, 70-79, and 80-89. Higher scores indicate better performance.
DKEFS Color Word Interference - Condition Three	Baseline, immediately post-treatment (after 12 study visits, around 4-6 weeks), and at follow-up (4 weeks after last treatment)	Delis-Kaplan Executive Function System (D-KEFS) Color Word Interference Test is used to assess cognitive flexibility and inhibitory control. Condition 3 is the traditional Stroop task, for which the examinee must inhibit reading the words in order to name the dissonant ink colors in which those words are printed. All D-KEFS raw scores are converted to scaled scores, with a mean of 10 and a standard deviation of 3, corrected for each of the following 16 age-groups:8, 9, 10, 11, 12, 13, 14, 15, 16-19, 20-29, 30-39, 40-49, 50-59, 60-69, 70-79, and 80-89. Higher scores indicate better performance.
DKEFS Verbal Fluency Test	Baseline, immediately post-treatment (after 12 study visits, around 4-6 weeks), and at follow-up (4 weeks after last treatment)	For the Delis-Kaplan Executive Function System (D-KEFS) Verbal Fluency Test (letter fluency), the examinee is asked to generate words that begin with a particular letter as quickly as possible in 60 seconds. The test measures the examinee's ability to generate words fluently in an effortful, phonemic format. All D-KEFS raw scores are converted to scaled scores, with a mean of 10 and a standard deviation of 3, corrected for each of the following 16 age-groups:8, 9, 10, 11, 12, 13, 14, 15, 16-19, 20-29, 30-39, 40-49, 50-59, 60-69, 70-79, and 80-89. Higher scores indicate better performance.
Digit Span Test	Baseline, immediately post-treatment (after 12 study visits, around 4-6 weeks), and at follow-up (4 weeks after last treatment)	The Digit Span test is a working memory test in which participants hear a sequence of numerical digits and are tasked to recall the sequence correctly, with increasingly longer sequences being tested in each trial. There are 14 spans of numbers, and each span is scored '1' (pass) or '0' (fail). Scores range from 0-14, with higher scores indicating better working memory.

Countries

United States

Participant flow

Recruitment details

Participants were recruited at a single academic medical center (UAB) from the Movement Disorders Clinic, local Parkinson support groups, and patient-advocacy channels between May 2023 and September 2024. All screening, intervention, and assessment visits occurred at the WHARF clinical research facility.

Pre-assignment details

44 individuals were screened; 25 attended in-person screening and completed informed consent, and 3 were excluded (cognitive/medical criteria). 22 eligible participants were therefore assigned to study arms.

Participants by arm

Arm	Count
Active taVNS + Exercise Participants who are randomized into the active taVNS + exercise group will receive 15 minutes of active taVNS prior to exercise sessions.	10
Sham taVNS + Exercise Participants who are randomized into the sham taVNS + exercise group will receive 0 mA of current for 15 minutes prior to exercise sessions.	10
Total	20

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Lost to Follow-up	1	0
Overall Study	Unrelated illness	0	1

Baseline characteristics

Characteristic	Sham taVNS + Exercise	Total	Active taVNS + Exercise
Age, Continuous	69.50 years STANDARD_DEVIATION 6.15	67.20 years STANDARD_DEVIATION 7.1	64.80 years STANDARD_DEVIATION 7.51
Hoehn & Yahr Stage	2.80 Scores on a scale STANDARD_DEVIATION 0.63	2.70 Scores on a scale STANDARD_DEVIATION 0.75	2.50 Scores on a scale STANDARD_DEVIATION 0.85
Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III	36.70 Scores on a scale STANDARD_DEVIATION 8.6	33.90 Scores on a scale STANDARD_DEVIATION 10.95	31.00 Scores on a scale STANDARD_DEVIATION 12.68
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Asian	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Black or African American	0 Participants	1 Participants	1 Participants
Race (NIH/OMB) More than one race	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) White	10 Participants	19 Participants	9 Participants
Sex: Female, Male Female	2 Participants	4 Participants	2 Participants
Sex: Female, Male Male	8 Participants	16 Participants	8 Participants
Years since diagnosis	4.80 years STANDARD_DEVIATION 3.05	5.00 years STANDARD_DEVIATION 3.18	5.20 years STANDARD_DEVIATION 3.47

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	0 / 10	0 / 10
other Total, other adverse events	0 / 10	0 / 10
serious Total, serious adverse events	0 / 10	0 / 10

Outcome results

Primary

Functional Gait Assessment (FGA)

The Functional Gait Assessment (FGA) is a clinical measure used to assess an individual's walking ability and functional mobility. It evaluates various aspects of gait, including balance, coordination, range of motion, and adaptability. The FGA consists of 10 different tasks or conditions that challenge the person's walking abilities in different ways, such as walking while turning, walking over obstacles, or walking with eyes closed. The scale title for the FGA is the total score, which ranges from 0 to 30. Higher scores on the FGA indicate better functional gait performance and greater walking independence. A score of 30 represents the best possible outcome, reflecting excellent gait function across all assessed conditions. Conversely, lower scores suggest impaired gait function and reduced functional mobility.