Trial Outcomes & Findings for Combining VNS With PT Interventions for Individuals With PD (NCT NCT05871151)

NCT ID: NCT05871151

Last Updated: 2025-12-17

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: NA
• Target enrollment: 25 participants
• Primary outcome timeframe: Baseline, immediately post-treatment (after 12 study visits, around 4-6 weeks), and at follow-up (4 weeks after last treatment)
• Results posted on: 2025-12-17

Participant Flow

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.

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.

Participant milestones

Measure	active taVNS + physical therapy Participants received bilateral transcutaneous auricular VNS using hydrogel earbud electrodes for 15 min at 30 Hz, 250 µs pulse width, 1-4 mA (adjusted for comfort) while seated at rest. Immediately afterwards they completed a 45-min one-on-one PWR! Moves® physical-therapy session with a PD-certified clinician. Twelve sessions were delivered over six weeks (2-3/wk) in the ON-medication state. Electrode sites were inspected before/after each use and vitals recorded pre-/post-stimulation and post-exercise.	sham taVNS + physical therapy The schedule, electrode placement, and clinical contact time were identical to the active arm, but the stimulation device delivered 0 mA current (no electrical output). Participants then completed the same 45-min PWR! Moves® sessions on the same timetable and under identical monitoring procedures.
Overall Study STARTED	11	11
Overall Study COMPLETED	10	10
Overall Study NOT COMPLETED	1	1

Reasons for withdrawal

Measure	active taVNS + physical therapy Participants received bilateral transcutaneous auricular VNS using hydrogel earbud electrodes for 15 min at 30 Hz, 250 µs pulse width, 1-4 mA (adjusted for comfort) while seated at rest. Immediately afterwards they completed a 45-min one-on-one PWR! Moves® physical-therapy session with a PD-certified clinician. Twelve sessions were delivered over six weeks (2-3/wk) in the ON-medication state. Electrode sites were inspected before/after each use and vitals recorded pre-/post-stimulation and post-exercise.	sham taVNS + physical therapy The schedule, electrode placement, and clinical contact time were identical to the active arm, but the stimulation device delivered 0 mA current (no electrical output). Participants then completed the same 45-min PWR! Moves® sessions on the same timetable and under identical monitoring procedures.
Overall Study Lost to Follow-up	1	0
Overall Study Unrelated illness	0	1

Baseline Characteristics

Combining VNS With PT Interventions for Individuals With PD

Baseline characteristics by cohort

Measure	Active taVNS + Exercise n=10 Participants Participants who are randomized into the active taVNS + exercise group will receive 15 minutes of active taVNS prior to exercise sessions.	Sham taVNS + Exercise n=10 Participants Participants who are randomized into the sham taVNS + exercise group will receive 0 mA of current for 15 minutes prior to exercise sessions.	Total n=20 Participants Total of all reporting groups
Sex: Female, Male Male	8 Participants n=6 Participants	8 Participants n=5 Participants	16 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=6 Participants	0 Participants n=5 Participants	0 Participants n=5 Participants
Age, Continuous	64.80 years STANDARD_DEVIATION 7.51 • n=6 Participants	69.50 years STANDARD_DEVIATION 6.15 • n=5 Participants	67.20 years STANDARD_DEVIATION 7.10 • n=5 Participants
Sex: Female, Male Female	2 Participants n=6 Participants	2 Participants n=5 Participants	4 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=6 Participants	0 Participants n=5 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=6 Participants	0 Participants n=5 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=6 Participants	0 Participants n=5 Participants	1 Participants n=5 Participants
Race (NIH/OMB) White	9 Participants n=6 Participants	10 Participants n=5 Participants	19 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=6 Participants	0 Participants n=5 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=6 Participants	0 Participants n=5 Participants	0 Participants n=5 Participants
Years since diagnosis	5.20 years STANDARD_DEVIATION 3.47 • n=6 Participants	4.80 years STANDARD_DEVIATION 3.05 • n=5 Participants	5.00 years STANDARD_DEVIATION 3.18 • n=5 Participants
Hoehn & Yahr Stage	2.50 Scores on a scale STANDARD_DEVIATION 0.85 • n=6 Participants	2.80 Scores on a scale STANDARD_DEVIATION 0.63 • n=5 Participants	2.70 Scores on a scale STANDARD_DEVIATION 0.75 • n=5 Participants
Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III	31.00 Scores on a scale STANDARD_DEVIATION 12.68 • n=6 Participants	36.70 Scores on a scale STANDARD_DEVIATION 8.60 • n=5 Participants	33.90 Scores on a scale STANDARD_DEVIATION 10.95 • n=5 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Measure	active taVNS + exercise n=10 Participants Participants who are randomized into the active taVNS + exercise group will receive 15 minutes of active taVNS prior to exercise sessions.	sham taVNS + exercise n=10 Participants Participants who are randomized into the sham taVNS + exercise group will receive 0 mA of current for 15 minutes prior to exercise sessions.
Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III Follow-up	24.5 Scores on a scale Standard Deviation 9.969397619	32.3 Scores on a scale Standard Deviation 8.525126262
Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III Baseline	31.00 Scores on a scale Standard Deviation 12.68419839	36.70 Scores on a scale Standard Deviation 8.602971063
Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III Post-treatment	25.1 Scores on a scale Standard Deviation 11.51279481	26.8 Scores on a scale Standard Deviation 12.51488003

PRIMARY outcome

Timeframe: Baseline, immediately post-treatment (after 12 study visits, around 4-6 weeks), and at follow-up (4 weeks after last treatment)

Population: One participant in the sham group and one in the active group did not complete the 6MWT at follow-up. One participant in the sham group did not complete the 6MWT at post-test.

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.

Outcome measures

Measure	active taVNS + exercise n=10 Participants Participants who are randomized into the active taVNS + exercise group will receive 15 minutes of active taVNS prior to exercise sessions.	sham taVNS + exercise n=10 Participants Participants who are randomized into the sham taVNS + exercise group will receive 0 mA of current for 15 minutes prior to exercise sessions.
Six Minute Walk Test (6MWT) Post-treatment	1566 feet Standard Deviation 196.4051934	1448.111111 feet Standard Deviation 323.8643406
Six Minute Walk Test (6MWT) Baseline	1411.94 feet Standard Deviation 137.6766598	1366 feet Standard Deviation 272.5831168
Six Minute Walk Test (6MWT) Follow-up	1544 feet Standard Deviation 204.1366645	1435 feet Standard Deviation 278.8480769

PRIMARY outcome

Timeframe: Baseline, immediately post-treatment (after 12 study visits, around 4-6 weeks), and at follow-up (4 weeks after last treatment)

Population: Self-selected gait speed

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.

Outcome measures

Measure	active taVNS + exercise n=10 Participants Participants who are randomized into the active taVNS + exercise group will receive 15 minutes of active taVNS prior to exercise sessions.	sham taVNS + exercise n=10 Participants Participants who are randomized into the sham taVNS + exercise group will receive 0 mA of current for 15 minutes prior to exercise sessions.
Ten Meter Walk Test (10MWT) Baseline	5.022333333 seconds Standard Deviation 0.584714872	5.101666667 seconds Standard Deviation 0.587701633
Ten Meter Walk Test (10MWT) Post-treatment	5.021333333 seconds Standard Deviation 0.671720105	5.309333333 seconds Standard Deviation 0.810643396
Ten Meter Walk Test (10MWT) Follow-up	5.103 seconds Standard Deviation 0.581786204	5.238 seconds Standard Deviation 0.691324012

PRIMARY outcome

Timeframe: 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.

Outcome measures

Measure	active taVNS + exercise n=10 Participants Participants who are randomized into the active taVNS + exercise group will receive 15 minutes of active taVNS prior to exercise sessions.	sham taVNS + exercise n=10 Participants Participants who are randomized into the sham taVNS + exercise group will receive 0 mA of current for 15 minutes prior to exercise sessions.
Mini-Best Test Follow-up	25.8 Scores on a scale Standard Deviation 2.043961296	22.2 Scores on a scale Standard Deviation 3.425395354
Mini-Best Test Baseline	22.3 Scores on a scale Standard Deviation 2.540778533	20.9 Scores on a scale Standard Deviation 3.754996671
Mini-Best Test Post-treatment	25.7 Scores on a scale Standard Deviation 1.159501809	22.8 Scores on a scale Standard Deviation 2.936362073

PRIMARY outcome

Timeframe: 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.

Outcome measures

Measure	active taVNS + exercise n=10 Participants Participants who are randomized into the active taVNS + exercise group will receive 15 minutes of active taVNS prior to exercise sessions.	sham taVNS + exercise n=10 Participants Participants who are randomized into the sham taVNS + exercise group will receive 0 mA of current for 15 minutes prior to exercise sessions.
Functional Gait Assessment (FGA) Baseline	25 Scores on a scale Standard Deviation 3.431876714	22.7 Scores on a scale Standard Deviation 4.083843506
Functional Gait Assessment (FGA) Post	28.6 Scores on a scale Standard Deviation 2.170509413	24.4 Scores on a scale Standard Deviation 3.438345856
Functional Gait Assessment (FGA) Follow-up	27.6 Scores on a scale Standard Deviation 2.796823595	24 Scores on a scale Standard Deviation 3.771236166

PRIMARY outcome

Timeframe: 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.

Outcome measures

Measure	active taVNS + exercise n=10 Participants Participants who are randomized into the active taVNS + exercise group will receive 15 minutes of active taVNS prior to exercise sessions.	sham taVNS + exercise n=10 Participants Participants who are randomized into the sham taVNS + exercise group will receive 0 mA of current for 15 minutes prior to exercise sessions.
mCTSIB Baseline	226 Scores on a scale Standard Deviation 87.32951646	182.2 Scores on a scale Standard Deviation 71.38907479
mCTSIB Post	217.4 Scores on a scale Standard Deviation 84.06505417	175.6 Scores on a scale Standard Deviation 59.470254
mCTSIB Follow-up	197.6 Scores on a scale Standard Deviation 68.44981941	197.1 Scores on a scale Standard Deviation 76.29249271

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	active taVNS + exercise n=10 Participants Participants who are randomized into the active taVNS + exercise group will receive 15 minutes of active taVNS prior to exercise sessions.	sham taVNS + exercise n=10 Participants Participants who are randomized into the sham taVNS + exercise group will receive 0 mA of current for 15 minutes prior to exercise sessions.
MoCA Baseline	27.2 Scores on a scale Standard Deviation 2.699794231	26.7 Scores on a scale Standard Deviation 1.946506843
MoCA Post	28 Scores on a scale Standard Deviation 2.538591035	26.7 Scores on a scale Standard Deviation 1.946506843
MoCA Follow-up	27.7 Scores on a scale Standard Deviation 1.888562063	27.9 Scores on a scale Standard Deviation 1.969207398

SECONDARY outcome

Timeframe: Baseline, immediately post-treatment (after 12 study visits, around 4-6 weeks), and at follow-up (4 weeks after last treatment)

Population: One participant in the sham group did not complete the CWI.

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.

Outcome measures

Measure	active taVNS + exercise n=10 Participants Participants who are randomized into the active taVNS + exercise group will receive 15 minutes of active taVNS prior to exercise sessions.	sham taVNS + exercise n=9 Participants Participants who are randomized into the sham taVNS + exercise group will receive 0 mA of current for 15 minutes prior to exercise sessions.
DKEFS Color Word Interference Test - Condition One Follow-up	10.6 Scores on a scale Standard Deviation 3.134042473	8 Scores on a scale Standard Deviation 2.390457219
DKEFS Color Word Interference Test - Condition One Baseline	8.888888889 Scores on a scale Standard Deviation 2.713136766	9.2 Scores on a scale Standard Deviation 3.938414797
DKEFS Color Word Interference Test - Condition One Post	10.3 Scores on a scale Standard Deviation 2.945806813	8.888888889 Scores on a scale Standard Deviation 1.96497102

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	active taVNS + exercise n=10 Participants Participants who are randomized into the active taVNS + exercise group will receive 15 minutes of active taVNS prior to exercise sessions.	sham taVNS + exercise n=9 Participants Participants who are randomized into the sham taVNS + exercise group will receive 0 mA of current for 15 minutes prior to exercise sessions.
DKEFS Color Word Interference Test - Condition Two Baseline	9.8 Scores on a scale Standard Deviation 3.259175083	9.111111111 Scores on a scale Standard Deviation 2.848001248
DKEFS Color Word Interference Test - Condition Two Post	10.6 Scores on a scale Standard Deviation 2.951459149	8.444444444 Scores on a scale Standard Deviation 2.920235911
DKEFS Color Word Interference Test - Condition Two Follow-up	10.7 Scores on a scale Standard Deviation 2.263232693	8.125 Scores on a scale Standard Deviation 3.313931631

SECONDARY outcome

Timeframe: Baseline, immediately post-treatment (after 12 study visits, around 4-6 weeks), and at follow-up (4 weeks after last treatment)

Population: One of the participants in the sham group did not complete CWI-3 at follow-up.

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.

Outcome measures

Measure	active taVNS + exercise n=10 Participants Participants who are randomized into the active taVNS + exercise group will receive 15 minutes of active taVNS prior to exercise sessions.	sham taVNS + exercise n=9 Participants Participants who are randomized into the sham taVNS + exercise group will receive 0 mA of current for 15 minutes prior to exercise sessions.
DKEFS Color Word Interference - Condition Three Baseline	10.5 Scores on a scale Standard Deviation 2.990726407	9.666666667 Scores on a scale Standard Deviation 2.645751311
DKEFS Color Word Interference - Condition Three Post	11.1 Scores on a scale Standard Deviation 3.281259921	8.333333333 Scores on a scale Standard Deviation 4.123105626
DKEFS Color Word Interference - Condition Three Follow-up	11.3 Scores on a scale Standard Deviation 3.020301677	9.625 Scores on a scale Standard Deviation 3.335416016

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	active taVNS + exercise n=10 Participants Participants who are randomized into the active taVNS + exercise group will receive 15 minutes of active taVNS prior to exercise sessions.	sham taVNS + exercise n=10 Participants Participants who are randomized into the sham taVNS + exercise group will receive 0 mA of current for 15 minutes prior to exercise sessions.
DKEFS Verbal Fluency Test Baseline	12.9 Scores on a scale Standard Deviation 4.040077007	9.1 Scores on a scale Standard Deviation 3.281259921
DKEFS Verbal Fluency Test Post	12.6 Scores on a scale Standard Deviation 4.247875286	8.6 Scores on a scale Standard Deviation 3.134042473
DKEFS Verbal Fluency Test Follow-up	12.9 Scores on a scale Standard Deviation 4.771442829	9.4 Scores on a scale Standard Deviation 3.864367132

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	active taVNS + exercise n=9 Participants Participants who are randomized into the active taVNS + exercise group will receive 15 minutes of active taVNS prior to exercise sessions.	sham taVNS + exercise n=9 Participants Participants who are randomized into the sham taVNS + exercise group will receive 0 mA of current for 15 minutes prior to exercise sessions.
Digit Span Test Baseline	10.44444444 Scores on a scale Standard Deviation 2.554951619	9.7 Scores on a scale Standard Deviation 2.790858092
Digit Span Test Post	10.66666667 Scores on a scale Standard Deviation 1.118033989	9.777777778 Scores on a scale Standard Deviation 2.43812314
Digit Span Test Follow-up	11.33333333 Scores on a scale Standard Deviation 1.802775638	11.33333333 Scores on a scale Standard Deviation 2.549509757

SECONDARY outcome

Timeframe: Baseline, immediately post-treatment (after 12 study visits, around 4-6 weeks), and at follow-up (4 weeks after last treatment)

Population: One participant in the sham group and one in the active group did not complete the DSST at post-test.

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.

Outcome measures

Measure	active taVNS + exercise n=10 Participants Participants who are randomized into the active taVNS + exercise group will receive 15 minutes of active taVNS prior to exercise sessions.	sham taVNS + exercise n=10 Participants Participants who are randomized into the sham taVNS + exercise group will receive 0 mA of current for 15 minutes prior to exercise sessions.
Digit Symbol Substitution Test Post	41.1 Scores on a scale Standard Deviation 12.75800402	38.9 Scores on a scale Standard Deviation 7.015063158
Digit Symbol Substitution Test Baseline	37.1 Scores on a scale Standard Deviation 9.848293704	39.2 Scores on a scale Standard Deviation 4.984420171
Digit Symbol Substitution Test Follow-up	39.4 Scores on a scale Standard Deviation 16.38563056	40.7 Scores on a scale Standard Deviation 6.583649781

SECONDARY outcome

Timeframe: 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

Outcome measures

Measure	active taVNS + exercise n=8 Participants Participants who are randomized into the active taVNS + exercise group will receive 15 minutes of active taVNS prior to exercise sessions.	sham taVNS + exercise n=8 Participants Participants who are randomized into the sham taVNS + exercise group will receive 0 mA of current for 15 minutes prior to exercise sessions.
Flanker Follow-up	103.5 Scores on a scale Standard Deviation 15.10912685	102.375 Scores on a scale Standard Deviation 16.12396176
Flanker Baseline	95.75 Scores on a scale Standard Deviation 15.70941483	99.25 Scores on a scale Standard Deviation 12.98075499
Flanker Post	102.75 Scores on a scale Standard Deviation 16.05125718	95.375 Scores on a scale Standard Deviation 16.8771824

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	active taVNS + exercise n=10 Participants Participants who are randomized into the active taVNS + exercise group will receive 15 minutes of active taVNS prior to exercise sessions.	sham taVNS + exercise n=10 Participants Participants who are randomized into the sham taVNS + exercise group will receive 0 mA of current for 15 minutes prior to exercise sessions.
Promise Neuro-QOL (Ability) Baseline	47.89 t-score Standard Deviation 4.497764877	52.97 t-score Standard Deviation 6.559141204
Promise Neuro-QOL (Ability) Post	49.71 t-score Standard Deviation 7.116561279	48.33 t-score Standard Deviation 5.303468467
Promise Neuro-QOL (Ability) Follow-up	48.95 t-score Standard Deviation 5.909925737	48.66 t-score Standard Deviation 4.927519096

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	active taVNS + exercise n=10 Participants Participants who are randomized into the active taVNS + exercise group will receive 15 minutes of active taVNS prior to exercise sessions.	sham taVNS + exercise n=10 Participants Participants who are randomized into the sham taVNS + exercise group will receive 0 mA of current for 15 minutes prior to exercise sessions.
SF-36 Baseline	67.26388889 Scores on a scale Standard Deviation 14.89936089	72.01388889 Scores on a scale Standard Deviation 14.33141466
SF-36 Post	69.31944445 Scores on a scale Standard Deviation 15.07532101	71 Scores on a scale Standard Deviation 9.948168137
SF-36 Follow-up	69.06944446 Scores on a scale Standard Deviation 18.55656392	73.4722222 Scores on a scale Standard Deviation 10.15821345

Adverse Events

active taVNS + exercise

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

sham taVNS + exercise

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Alexandra Evancho

University of Alabama at Birmingham

Phone: (205)975-5221

Email: amelgin@uab.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place