Trial Outcomes & Findings for Electrical Stimulation to Promote Recovery in Bells Palsy (NCT NCT03836989)

NCT ID: NCT03836989

Last Updated: 2021-05-11

Results Overview

To evaluate for complete recovery, standardized photos of patients at rest, and during movement, will be evaluated by three treatment-blinded otolaryngologists. Total number of patients fully recovered over number of participants will be reported.

• Recruitment status: TERMINATED
• Study phase: NA
• Target enrollment: 4 participants
• Primary outcome timeframe: 3 months
• Results posted on: 2021-05-11

Participant Flow

Blocks were designed to account for predictors of recovery. There were four allocation blocks: 1) >60 age with complete paralysis, 2) > 60 age with incomplete paralysis, 3) <60 age with complete paralysis and < 15 days duration, or 4) <60 age with complete paralysis and >15 days duration. The block size was 2 and the allocation was 1:1. All patients were randomly allocated to high-volt arm

Participant milestones

Measure	High-volt Electrical Stimulation Plan to use a monophasic waveform having 100µmsec pulse duration, at 35 Hz using tolerated voltage to generate a contraction a total of 20 minutes. The stimulation will have 10 seconds on time, 30 seconds off time and 2 second ramp up and down. Electrical stimulation will be produced with the Orthostim 3 device (VQ Ortho Care). The cathode will be placed on the ipsilateral muscle to stimulate and the anode over the ipsilateral mastoid region. Four facial muscles will be stimulated: 1)frontalis, 2) orbicularis oculi, 3) zygomaticus major, and 4) orbicularis oris. The voltage is turned up by the participant until he or she can see twitches or as high as tolerated. Ten contractions in each muscle group will be performed or 5 minutes per muscle if no contraction is achieved.	Subsensory Electrical Stimulation Plan to use the same device and settings to provide placebo treatment by delivering minimal electricity. The settings will be the same as the intervention except the voltage will be subsensory. ie. below the minimum at which patients feels any effect of the current. The voltage is turned down two clicks from the voltage at which the participant can first notice any electricity or at the minimal setting.
Overall Study STARTED	4	0
Overall Study Subjects > 60 Years Old With Complete Paralysis	1	0
Overall Study Subjects > 60 Years Old With Incomplete Paralysis	1	0
Overall Study Subject < 60 Years Old + Complete Paralysis < 15 Days Duration	1	0
Overall Study Subjects < 60 Years Old + Complete Paralysis > 15 Days	1	0
Overall Study COMPLETED	4	0
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Measure	High-volt Electrical Stimulation n=4 Participants Plan to use a monophasic waveform having 100µmsec pulse duration, at 35 Hz using tolerated voltage to generate a contraction a total of 20 minutes. The stimulation will have 10 seconds on time, 30 seconds off time and 2 second ramp up and down. Electrical stimulation will be produced with the Orthostim 3 device (VQ Ortho Care). The cathode will be placed on the ipsilateral muscle to stimulate and the anode over the ipsilateral mastoid region. Four facial muscles will be stimulated: 1)frontalis, 2) orbicularis oculi, 3) zygomaticus major, and 4) orbicularis oris. The voltage is turned up by the participant until he or she can see twitches or as high as tolerated. Ten contractions in each muscle group will be performed or 5 minutes per muscle if no contraction is achieved	Subsensory Electrical Stimulation Plan to use the same device and settings to provide placebo treatment by delivering minimal electricity. The settings will be the same as the intervention except the voltage will be subsensory. ie. below the minimum at which patients feels any effect of the current. The voltage is turned down two clicks from the voltage at which the participant can first notice any electricity or at the minimal setting.	Total n=4 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=4 Participants	—	0 Participants n=4 Participants
Age, Categorical Between 18 and 65 years	2 Participants n=4 Participants	—	2 Participants n=4 Participants
Age, Categorical >=65 years	2 Participants n=4 Participants	—	2 Participants n=4 Participants
Sex: Female, Male Female	3 Participants n=4 Participants	—	3 Participants n=4 Participants
Sex: Female, Male Male	1 Participants n=4 Participants	—	1 Participants n=4 Participants
Race and Ethnicity Not Collected	—	—	0 Participants Race and Ethnicity were not collected from any participant.
Region of Enrollment United States	4 Participants n=4 Participants	—	4 Participants n=4 Participants

PRIMARY outcome

Timeframe: 3 months

Population: Randomization led to no Subsensory participants.

To evaluate for complete recovery, standardized photos of patients at rest, and during movement, will be evaluated by three treatment-blinded otolaryngologists. Total number of patients fully recovered over number of participants will be reported.

Outcome measures

Measure	High-volt Electrical Stimulation n=4 Participants Plan to use a monophasic waveform having 100µmsec pulse duration, 35 Hz and using tolerated voltage for a total of 20 minutes. Electrical stimulation will be produced with the Orthostim 3 device. The cathode will be placed on the ipsilateral muscle to stimulate and the anode over the ipsilateral arm. The voltage is turned up by the participant until he or she can see twitches or as high as tolerated.	Subsensory Electrical Stimulation Plan to use the same device and settings to provide placebo treatment by delivering minimal electricity. The settings will be the same as the intervention except the voltage will be subsensory. ie. below the minimum at which patients feels any effect of the current. The voltage is turned down two clicks from the voltage at which the participant can first notice any electricity or at the minimal setting.
Recovery at 3 Months as Measured From Facial Photos With Different Facial Expressions	3 Participants	—

SECONDARY outcome

Timeframe: Baseline, and 3 months

Population: No subjects underwent subsensory electrical stimulation

Determined by three blinded otolaryngologist reviewing facial photos of patients with smile and eye closure. Reported as an average of the three scores. The scales ranges from 1 (normal) to 6 (most severe dysfunction)

Outcome measures

Measure	High-volt Electrical Stimulation n=4 Participants Plan to use a monophasic waveform having 100µmsec pulse duration, 35 Hz and using tolerated voltage for a total of 20 minutes. Electrical stimulation will be produced with the Orthostim 3 device. The cathode will be placed on the ipsilateral muscle to stimulate and the anode over the ipsilateral arm. The voltage is turned up by the participant until he or she can see twitches or as high as tolerated.	Subsensory Electrical Stimulation Plan to use the same device and settings to provide placebo treatment by delivering minimal electricity. The settings will be the same as the intervention except the voltage will be subsensory. ie. below the minimum at which patients feels any effect of the current. The voltage is turned down two clicks from the voltage at which the participant can first notice any electricity or at the minimal setting.
House Brackmann Scale 3 months	2 score on a scale Standard Deviation 1.15	—
House Brackmann Scale Baseline	5.5 score on a scale Standard Deviation 1	—

SECONDARY outcome

Timeframe: Baseline, 3 months and 6 months

Population: No research subjects participated in the subsensory electrical stimulation arm

Quality of life is in part measured in this study using the patient reported Synkinesis Assessment Questionnaire (SAQ). The instrument consisting of 10 items asks participants how difficult certain facial activities are. Based on the average score for each domain the test gives a score between 20 (no synkinesis) to 100 (severe synkinesis, all the time).

Outcome measures

Measure	High-volt Electrical Stimulation n=4 Participants Plan to use a monophasic waveform having 100µmsec pulse duration, 35 Hz and using tolerated voltage for a total of 20 minutes. Electrical stimulation will be produced with the Orthostim 3 device. The cathode will be placed on the ipsilateral muscle to stimulate and the anode over the ipsilateral arm. The voltage is turned up by the participant until he or she can see twitches or as high as tolerated.	Subsensory Electrical Stimulation Plan to use the same device and settings to provide placebo treatment by delivering minimal electricity. The settings will be the same as the intervention except the voltage will be subsensory. ie. below the minimum at which patients feels any effect of the current. The voltage is turned down two clicks from the voltage at which the participant can first notice any electricity or at the minimal setting.
Patient Reported Quality of Life in Relation to Facial Synkinesis Measured by the Synkinesis Assessment Questionnaire (SAQ) 3 month outcome	27.5 score on a scale Standard Deviation 5.25	—
Patient Reported Quality of Life in Relation to Facial Synkinesis Measured by the Synkinesis Assessment Questionnaire (SAQ) 6 month outcome	38.7 score on a scale Standard Deviation 23.5	—
Patient Reported Quality of Life in Relation to Facial Synkinesis Measured by the Synkinesis Assessment Questionnaire (SAQ) Baseline	31 score on a scale Standard Deviation 7.7	—

SECONDARY outcome

Timeframe: Baseline, 3 months and 6 months

Population: No subjects were recruited for the subsensory arm

Measured by the validated quality of life patient reported questionnaire Facial Clinimetric Evaluation (FaCE) Scale with a scale from 0 (normal) to 100 (severe dysfunction). The scale encompasses facial movement, facial comfort, oral function, eye comfort, lacrimal control, and social function.

Outcome measures

Measure	High-volt Electrical Stimulation n=4 Participants Plan to use a monophasic waveform having 100µmsec pulse duration, 35 Hz and using tolerated voltage for a total of 20 minutes. Electrical stimulation will be produced with the Orthostim 3 device. The cathode will be placed on the ipsilateral muscle to stimulate and the anode over the ipsilateral arm. The voltage is turned up by the participant until he or she can see twitches or as high as tolerated.	Subsensory Electrical Stimulation Plan to use the same device and settings to provide placebo treatment by delivering minimal electricity. The settings will be the same as the intervention except the voltage will be subsensory. ie. below the minimum at which patients feels any effect of the current. The voltage is turned down two clicks from the voltage at which the participant can first notice any electricity or at the minimal setting.
Patient Reported Global Quality of Life Specific to Facial Paralysis Baseline	37.5 score on a scale Standard Deviation 3.4	—
Patient Reported Global Quality of Life Specific to Facial Paralysis 3 months	51.25 score on a scale Standard Deviation 12.03	—
Patient Reported Global Quality of Life Specific to Facial Paralysis 6 months	51 score on a scale Standard Deviation 15	—

SECONDARY outcome

Timeframe: Baseline and in 3 months

Population: No subjects were allocated to the subsensory arm

Measuring brow elevation using the MEEI FACE-gram program reported as the millimeters in decreased elevation in comparison to the unaffected side

Outcome measures

Measure	High-volt Electrical Stimulation n=4 Participants Plan to use a monophasic waveform having 100µmsec pulse duration, 35 Hz and using tolerated voltage for a total of 20 minutes. Electrical stimulation will be produced with the Orthostim 3 device. The cathode will be placed on the ipsilateral muscle to stimulate and the anode over the ipsilateral arm. The voltage is turned up by the participant until he or she can see twitches or as high as tolerated.	Subsensory Electrical Stimulation Plan to use the same device and settings to provide placebo treatment by delivering minimal electricity. The settings will be the same as the intervention except the voltage will be subsensory. ie. below the minimum at which patients feels any effect of the current. The voltage is turned down two clicks from the voltage at which the participant can first notice any electricity or at the minimal setting.
Objective Measurements of Brow Elevation Baseline	7.75 millimeters Standard Deviation 2.2	—
Objective Measurements of Brow Elevation 3 months	4.5 millimeters Standard Deviation 5.2	—

SECONDARY outcome

Timeframe: Baseline and 3 months

Population: No subjects were allocated to the subsensory arm

Measuring in millimeters of the eyelids remaining open during maximal eye closure using the MEEI FACE-gram program

Outcome measures

Measure	High-volt Electrical Stimulation n=4 Participants Plan to use a monophasic waveform having 100µmsec pulse duration, 35 Hz and using tolerated voltage for a total of 20 minutes. Electrical stimulation will be produced with the Orthostim 3 device. The cathode will be placed on the ipsilateral muscle to stimulate and the anode over the ipsilateral arm. The voltage is turned up by the participant until he or she can see twitches or as high as tolerated.	Subsensory Electrical Stimulation Plan to use the same device and settings to provide placebo treatment by delivering minimal electricity. The settings will be the same as the intervention except the voltage will be subsensory. ie. below the minimum at which patients feels any effect of the current. The voltage is turned down two clicks from the voltage at which the participant can first notice any electricity or at the minimal setting.
Eye Closure Baseline	2.5 millimeters Standard Deviation 3.1	—
Eye Closure 3 months	0.5 millimeters Standard Deviation 0.6	—

SECONDARY outcome

Timeframe: Baseline and 3 months

Population: No subjects were allocated to the subsensory arm

Measuring oral commissure exclusion using the MEEI FACE-gram program reported as the change in millimeters in the distance between the midline of the lower lip and the oral commissure in comparison between rest and smile

Outcome measures

Measure	High-volt Electrical Stimulation n=4 Participants Plan to use a monophasic waveform having 100µmsec pulse duration, 35 Hz and using tolerated voltage for a total of 20 minutes. Electrical stimulation will be produced with the Orthostim 3 device. The cathode will be placed on the ipsilateral muscle to stimulate and the anode over the ipsilateral arm. The voltage is turned up by the participant until he or she can see twitches or as high as tolerated.	Subsensory Electrical Stimulation Plan to use the same device and settings to provide placebo treatment by delivering minimal electricity. The settings will be the same as the intervention except the voltage will be subsensory. ie. below the minimum at which patients feels any effect of the current. The voltage is turned down two clicks from the voltage at which the participant can first notice any electricity or at the minimal setting.
Smile Excursion Baseline	-1 millimeters Standard Deviation 1.15	—
Smile Excursion 3 months	4.5 millimeters Standard Deviation 3.5	—

SECONDARY outcome

Timeframe: Baseline and 3 months

Population: No subjects were allocated to the subsensory arm

Measured by facial asymmetry index (FAI) at rest in photos which is calculated as the difference in the distance from the lateral canthus to the oral commissure between the affected and unaffected side. In the scale 0 equals no difference between sides and perfect symmetry. The closer a number is to 0, the higher the symmetry is. Ranges have not been published for this scale. FAI does not have a maximum score.

Outcome measures

Measure	High-volt Electrical Stimulation n=4 Participants Plan to use a monophasic waveform having 100µmsec pulse duration, 35 Hz and using tolerated voltage for a total of 20 minutes. Electrical stimulation will be produced with the Orthostim 3 device. The cathode will be placed on the ipsilateral muscle to stimulate and the anode over the ipsilateral arm. The voltage is turned up by the participant until he or she can see twitches or as high as tolerated.	Subsensory Electrical Stimulation Plan to use the same device and settings to provide placebo treatment by delivering minimal electricity. The settings will be the same as the intervention except the voltage will be subsensory. ie. below the minimum at which patients feels any effect of the current. The voltage is turned down two clicks from the voltage at which the participant can first notice any electricity or at the minimal setting.
Facial Symmetry at Rest Baseline	0.25 score on a scale Standard Deviation 0.2	—
Facial Symmetry at Rest 3 months	0.02 score on a scale Standard Deviation 0	—

SECONDARY outcome

Timeframe: Baseline and 3 months

Population: no subjects were allocated to the subsensory arm

Measured by facial asymmetry index (FAI) during smile in photos which is calculated as the difference in the distance from the lateral canthus to the oral commissure between the affected and unaffected side. In the scale 0 equals perfect symmetry and no difference in sides. The closer a number is to 0, the greater the symmetry. Ranges have not been published for this scale. FAI does not have a maximum score.

Outcome measures

Measure	High-volt Electrical Stimulation n=4 Participants Plan to use a monophasic waveform having 100µmsec pulse duration, 35 Hz and using tolerated voltage for a total of 20 minutes. Electrical stimulation will be produced with the Orthostim 3 device. The cathode will be placed on the ipsilateral muscle to stimulate and the anode over the ipsilateral arm. The voltage is turned up by the participant until he or she can see twitches or as high as tolerated.	Subsensory Electrical Stimulation Plan to use the same device and settings to provide placebo treatment by delivering minimal electricity. The settings will be the same as the intervention except the voltage will be subsensory. ie. below the minimum at which patients feels any effect of the current. The voltage is turned down two clicks from the voltage at which the participant can first notice any electricity or at the minimal setting.
Facial Symmetry During Smile Baseline	0.4 score on a scale Standard Deviation 0.6	—
Facial Symmetry During Smile 3 months	0.2 score on a scale Standard Deviation 0.19	—

SECONDARY outcome

Timeframe: 3 months

Population: No subjected were recruited for the subsensory arm

Measured by a visual analog scale (VAS) which ranged from 0 to 10 where 0 stands for completely comfortable and 10 to very uncomfortable. A questionnaire designed by research team using a Likert's scale was created to measure patient tolerability.

Outcome measures

Measure	High-volt Electrical Stimulation n=4 Participants Plan to use a monophasic waveform having 100µmsec pulse duration, 35 Hz and using tolerated voltage for a total of 20 minutes. Electrical stimulation will be produced with the Orthostim 3 device. The cathode will be placed on the ipsilateral muscle to stimulate and the anode over the ipsilateral arm. The voltage is turned up by the participant until he or she can see twitches or as high as tolerated.	Subsensory Electrical Stimulation Plan to use the same device and settings to provide placebo treatment by delivering minimal electricity. The settings will be the same as the intervention except the voltage will be subsensory. ie. below the minimum at which patients feels any effect of the current. The voltage is turned down two clicks from the voltage at which the participant can first notice any electricity or at the minimal setting.
Patient Tolerability	2.7 score on a scale Standard Deviation 2.3	—

SECONDARY outcome

Timeframe: 3 months

Population: no subjects were recruited to the subsensory electrical stimulation

Percentage of subjected who reported full adherence, partial adherence and non-adherence confirmed by comparing to the daily diary of use.

Outcome measures

Measure	High-volt Electrical Stimulation n=4 Participants Plan to use a monophasic waveform having 100µmsec pulse duration, 35 Hz and using tolerated voltage for a total of 20 minutes. Electrical stimulation will be produced with the Orthostim 3 device. The cathode will be placed on the ipsilateral muscle to stimulate and the anode over the ipsilateral arm. The voltage is turned up by the participant until he or she can see twitches or as high as tolerated.	Subsensory Electrical Stimulation Plan to use the same device and settings to provide placebo treatment by delivering minimal electricity. The settings will be the same as the intervention except the voltage will be subsensory. ie. below the minimum at which patients feels any effect of the current. The voltage is turned down two clicks from the voltage at which the participant can first notice any electricity or at the minimal setting.
Self Reported Subject Adherence Non adherence	0 Participants	—
Self Reported Subject Adherence Full adherence	4 Participants	—
Self Reported Subject Adherence Partial adherence	0 Participants	—

Adverse Events

High-volt Electric Stimulation

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Subsensory Electric Stimulation

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	High-volt Electric Stimulation n=4 participants at risk Plan to use a monophasic waveform having 100µmsec pulse duration, at 35 Hz using tolerated voltage to generate a contraction a total of 20 minutes. The stimulation will have 10 seconds on time, 30 seconds off time and 2 second ramp up and down. Electrical stimulation will be produced with the Orthostim 3 device (VQ Ortho Care). The cathode will be placed on the ipsilateral muscle to stimulate and the anode over the ipsilateral mastoid region. Four facial muscles will be stimulated: 1)frontalis, 2) orbicularis oculi, 3) zygomaticus major, and 4) orbicularis oris. The voltage is turned up by the participant until he or she can see twitches or as high as tolerated. Ten contractions in each muscle group will be performed or 5 minutes per muscle if no contraction is achieved	Subsensory Electric Stimulation Plan to use the same device and settings to provide placebo treatment by delivering minimal electricity. The settings will be the same as the intervention except the voltage will be subsensory. ie. below the minimum at which patients feels any effect of the current. The voltage is turned down two clicks from the voltage at which the participant can first notice any electricity or at the minimal setting.
Nervous system disorders Pain	25.0% 1/4 • Number of events 1 • Adverse event data will be collected throughout the participants therapy. Therapy is to start during the first week of onset of facial paralysis and be used daily for three months or sooner until complete recovery is achieved. Adverse event data was collected for up to 3 months No participants were enrolled in the subsensory stimulation.	— 0/0 • Adverse event data will be collected throughout the participants therapy. Therapy is to start during the first week of onset of facial paralysis and be used daily for three months or sooner until complete recovery is achieved. Adverse event data was collected for up to 3 months No participants were enrolled in the subsensory stimulation.
Nervous system disorders Headache	25.0% 1/4 • Adverse event data will be collected throughout the participants therapy. Therapy is to start during the first week of onset of facial paralysis and be used daily for three months or sooner until complete recovery is achieved. Adverse event data was collected for up to 3 months No participants were enrolled in the subsensory stimulation.	— 0/0 • Adverse event data will be collected throughout the participants therapy. Therapy is to start during the first week of onset of facial paralysis and be used daily for three months or sooner until complete recovery is achieved. Adverse event data was collected for up to 3 months No participants were enrolled in the subsensory stimulation.
Skin and subcutaneous tissue disorders Skin irritation	25.0% 1/4 • Adverse event data will be collected throughout the participants therapy. Therapy is to start during the first week of onset of facial paralysis and be used daily for three months or sooner until complete recovery is achieved. Adverse event data was collected for up to 3 months No participants were enrolled in the subsensory stimulation.	— 0/0 • Adverse event data will be collected throughout the participants therapy. Therapy is to start during the first week of onset of facial paralysis and be used daily for three months or sooner until complete recovery is achieved. Adverse event data was collected for up to 3 months No participants were enrolled in the subsensory stimulation.

Additional Information

Dr. Myriam Loyo

Oregon Health and Science University

Phone: 503-494-8510

Email: loyo@ohsu.edu

Results disclosure agreements

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