Fatigue Syndrome, Chronic, Gait, Unsteady, Post-Acute COVID-19 Syndrome, Postacute Sequelae of Sars-CoV-2, Widespread Chronic Pain
Conditions
Keywords
Transcutaneous nerve electrical stimulation, Pain, Fatigue
Brief summary
The purpose of the pilot study is to examine acceptability and proof of concept effectiveness of a wireless TENS technology to address PASC associated FM. Sample size (n=30) is convenient and designed to explore acceptability and feasibility. Participants, who satisfy the inclusion and exclusion criteria and sign the informed consent form will be randomly assigned with ratio of 1:1 into two groups. One group will utilize TENS high-dose devices (Intervention group, IG); the other group will utilize TENS low-dose devices (Placebo group, PG). The baseline measurements will be performed, and the patients will take the programmed device home for a duration of 4 weeks. Then, the patients will come back after four weeks (4W). At this 4th week visit, both groups will be unblinded and the IG will keep their high-dose TENS device and the PG group will switch from a low-dose TENS to a high-dose TENS device. Both groups will continue to deliver 3-5 hour of stimulation daily, until their final 8th week follow up visit (8W). The primary outcome will be pain. Secondary outcomes include fatigue, limb strength and perfusion, gait assessment (cadence, stride time, double support), balance, pulse oximetry, and quality of life. The coordinator will utilize a weekly spreadsheet showing utilization (therapy sessions/day, logged in the Quell health Cloud) so compliance can be monitored and those that are not using the device can be encouraged.
Detailed description
Postacute Sequelae of Sars-CoV-2 (PASC) is an emerging entity that has been clearly recognized by musculoskeletal pain, fatigue, cognitive, and sleep disturbances, among other symptoms, in patients who have recovered from severe Sars-CoV-2 infection. Hospitalized survivors have reported a significant excess burden of many of these symptoms up to 8 months after discharge. Particularly in the lower extremity, musculoskeletal illness has been associated with prolonged immobilization, high-risk comorbidities, and the use of glucocorticoids that is commonly administered to these patients. These manifestations are the cardinal symptoms of fibromyalgia (FM), a condition thought to be caused by hyperactive sensory signaling due to central sensitization as well as deficient endogenous pain inhibition, triggered among others, by viral infections. Consequently, FM sequelae are one of the most common long-term complications seen in PASC. Thus, it is expected to impose a serious burden on different medical specialties in a near future. In a population that has persistent lack of symptom resolution such as FM, adherence to therapy could be challenging. Patients with constant pain, fatigue, and sleep disturbances, are difficult to keep motivated, especially those pain-medication dependents that often present low quality of life. One practical solution to address the symptomatology characteristic of FM is the use of transcutaneous electrical stimulation therapy (TENS). Studies have demonstrated its ability to manage pain and fatigue in patients with peripheral neuropathy and FM, and has shown to effectively improve lower-extremity perfusion and oxygen delivery in patients with ischemic lesions. However, TENS has not yet been explored for PASC. Since this technology is dose-dependent, the investigators propose a practical daily-basis therapy that patients with persistent associated FM due to previous COVID-19 infection could apply at home, thus, addressing PASC without relying only on medication. In this matter, Neurometrix Inc. (Woburn, MA, USA) has created a wireless TENS device (Quell®) to address pain, gait, sleep, and fatigue. This technology is placed in the lower-extremity and works through the stimulation of nerves that carry non-painful sensations (A-beta fibers) by closing a neurological gate in the spinal cord, thus, reducing transmission from pain nerves (A-delta and C fibers) to the brain. This device utilizes a wireless technology manageable through a smart phone application (Quell App) that also tracks symptom-status. Moreover, Baylor College of Medicine has created the Post-COVID-19 Clinic (McNair Campus, BCM St Luke's, Houston, TX, USA) supervised by specialists in critical and pulmonary care. This Clinic has a high volume of patients that present with PASC, particularly those with associated FM (i.e., persistent muscle pain, fatigue, weakness, atrophy, sleep problems, and/or anxiety). Therefore, the investigators believe Baylor institution is a suitable place to perform this pilot study.
Interventions
DEVICETENS - high-dose
Subjects will receive a functional TENS device (delivers 100% of the dose) to wear for 3-5 hours per day.
DEVICETENS - low-dose
Subjects will receive a placebo TENS device (delivers 10% of the dose) to wear for 3-5 hours per day.
Sponsors
NeuroMetrix, Inc.
Baylor College of Medicine
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
SUPPORTIVE_CARE
Masking
DOUBLE (Subject, Caregiver)
Masking description
Devices may be high-dose (delivering 100% of the dose) or low-dose (delivering 10% of the dose) TENS
Intervention model description
Participants, who satisfy the inclusion and exclusion criteria and sign the informed consent form will be randomly assigned with ratio of 1:1 into two groups. One group will utilize TENS high-dose devices (Intervention group, IG); the other group will utilize TENS low-dose devices (Placebo group, PG). Both groups will receive their respective devices at the initial visit (BL) and will be asked to return in 4 weeks for follow-up assessment (4W visit). At this 4 week visit, study participants will be unblinded and the IG will keep their high-dose device, while the PG will switch from low-dose to high-dose TENS device. Study participants will return for a final in-person visit at the 8th week (8W), which will include the assessments described above. Throughout this 8-week period the participants may receive follow-up phone calls assessing their compliance. All subjects will keep the commercial (high-dose TENS) device after completion of the 8-week study.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Previous COVID-19 infection * Persistent symptoms of pain, fatigue, weakness, or poor gait and balance that were not present before COVID-19 infection * Willing to attend clinic for assessments
Exclusion criteria
* Severe cognitive decline reduces their ability to interact with the TENS mobile app * Major visual or hearing weakness reduces the ability to interact with TENS mobile app * Unable to walk independently for a distance of 10 meter * Major foot problems such as active lower extremity wounds, major foot deformity (e.g., Charcot Foot), previous major amputations, and claudication * Demand-type cardiac pacemaker, implanted defibrillator, or other implanted electronic devices; and any conditions that may interfere with outcomes or increase the risk of the use TENS based on the judgement of clinicians
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change in Functional Interference From Pain From Baseline to 4 Weeks (Blinded Phase) | baseline to 4 weeks | Pain will be assessed with a validated questionnaire called Brief Pain Inventory interference composite score (BPI-I). The maximum score is 10, meaning pain completely interferes, while the minimum score is zero, meaning pain does not interfere. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change in Functional Interference From Fatigue From Baseline to 4 Weeks (Blinded Phase) | Baseline to 4 weeks | Functional interference from fatigue will be assessed calculating the Global Fatigue Index (GFI) obtained from a validated questionnaire called Multidimensional Assessment Fatigue, which has a minimum score of 0 (no fatigue) and a maximum sore of 100 (severe fatigue). |
| Stride Time at 4 Weeks During a Simple Walking Task (Blinded Phase) | at 4 weeks | Stride time will be measured with wearable sensors (LEGSys, BioSensics, MA) during a free walking task (single task) using normal pace for 30 ft. Stride time is defined as the period elapsed between the first contact of two consecutive footsteps of the same foot expressed in seconds. |
| Cadence at 4 Weeks During a Simple Walking Task (Blinded Phase) | at 4 weeks | Cadence will be measured with wearable sensors (LEGSys, BioSensics, MA) during a free walking task (single task) using normal pace for 30 ft. Cadence is defined as rate of number of steps per minute. |
| Mean Change in Pain Severity From Baseline to 4 Weeks (Blinded Phase) | Baseline to 4 weeks | Pain severity will be assessed using the Brief Pain Inventory questionnaire composite score for severity. The maximum score is 10, meaning pain as bad as one can imagine, while the minimum score is zero, meaning no pain. |
| Cadence at 4 Weeks During a Dual Walking Task (Blinded Phase) | at 4 weeks | Cadence will be measured with wearable sensors (LEGSys, BioSensics, MA) during a dual walking task (participants asked to count backwards by two while walking) using normal pace for 30 ft. Cadence is defined as rate of number of steps per minute. |
| Cadence at 4 Weeks During a Fast Walking Task (Blinded Phase) | at 4 weeks | Cadence will be measured with wearable sensors (LEGSys, BioSensics, MA) during a fast walking task (participants asked to walk at a slightly faster pace) for 30 ft. Cadence is defined as rate of number of steps per minute. |
| Double Support Phase at 4 Weeks During a Simple Walking Task (Blinded Phase) | at 4 weeks | Double Support Phase will be measured with wearable sensors (LEGSys, BioSensics, MA) during a free walking task (single task) using normal pace for 30 ft. Double support phase is defined as percentage time when both feet are simultaneously in contact with the ground during a single stride. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Sleep Duration at 4 Weeks (Blinded Phase) | up to 4 weeks | Daily sleep duration in hours obtained with the mean 90 percentile will be measured over the course of the 4 weeks using a smart watch (Vivosmart 4, Garmin, US) |
| Sural Nerve Amplitude at 4 Weeks (Blinded Phase) | at 4 weeks | Sural nerve amplitude will be assessed with a DPN Check device (Neurometrix Inc, MA). The device elicits a electrical stimulation upon contact with the skin on the ankle area and returns values that can range from a minimum of 0 microVolts to a maximum of 32 microVolts. Measurements will be obtained at 4 weeks. |
| Mean Change in Functional Interference From Pain at 8 Weeks (Unblinded Phase) | from week 4 to week 8 | Pain will be assessed with a validated questionnaire called Brief Pain Inventory interference composite score (BPI-I). The maximum score is 10, meaning pain completely interferes, while the minimum score is zero, meaning pain does not interfere. This outcome assesses the difference between the mean BPI interference composite score at week 8 and week 4. |
| Mean Change in Pain Severity From 4 Weeks to 8 Weeks (Unblinded Phase) | 4 weeks to 8 weeks | Pain severity will be assessed using the Brief Pain Inventory questionnaire composite score for severity. The maximum score is 10, meaning pain as bad as one can imagine, while the minimum score is zero, meaning no pain. This outcome assesses the difference between the mean BPI severity composite score at week 8 and week 4. |
| Mean Change in Functional Interference From Fatigue From 4 Weeks to 8 Weeks (Unblinded Phase) | 4 weeks to 8 weeks | Functional interference from fatigue will be assessed calculating the Global Fatigue Index (GFI) obtained from a validated questionnaire called Multidimensional Assessment Fatigue, which has a minimum score of 0 (no fatigue) and a maximum sore of 100 (severe fatigue). This outcome assesses the difference between the mean global fatigue index at week 8 and week 4. |
| Stride Time at 8 Weeks During a Simple Walking Task (Unblinded Phase) | at 8 weeks | Stride time will be measured with wearable sensors (LEGSys, BioSensics, MA) during a free walking task (single task) using normal pace for 30 ft. Stride time is defined as the period elapsed between the first contact of two consecutive footsteps of the same foot expressed in seconds. |
| Gastrocnemius Muscle Endurance (Muscle Sustained Contraction) in Response to Electrical Stimulation at 8 Weeks (Unblinded Phase) | at 8 weeks | Gastrocnemius muscle endurance in response to 5 minutes of electrical stimulation therapy will be assessed with surface electromyography using a validated non-invasive device (Delsys Trino Wireless EMG System, MA, US). |
| Frailty at 8 Weeks (Unblinded Phase) | at 8 weeks | Frailty will be measured with an upper-extremity wearable sensor (Frailty meter, BioSensics, MA) which enables a frailty index score based on a validated algorithm. Patients with frailty index \>0.27 is considered are considered as frail. Patients with a frailty index \<0.27 are considered as non-frail. The higher the frailty index, the higher the level of frailty. The frailty index ranges from 0-1. |
| Sural Nerve Conduction Velocity at 8 Weeks (Unblinded Phase) | at 8 weeks | Sural nerve conduction will be assessed with a DPN Check device (Neurometrix Inc, MA). The device elicits a electrical stimulation upon contact with the skin on the ankle area and returns values that can range from a minimum of 20 m/s to a maximum of 60m/s. Measurements will be obtained at 8 weeks and value will be compared between groups. |
| Ankle Strength at 8 Weeks (Unblinded Phase) | at 8 weeks | Ankle strength will be assessed with an ankle dynamometer. Participants will be asked to perform 3 maximum voluntary contractions (MVC) sustaining ankle dorsiflexion for 5 seconds with 30 seconds of resting in between MVCs. The average of the 3 MVCs will then be calculated per lower extremity. |
| Plantar Tissue Oxygen Saturation at 8 Weeks (Unblinded Phase) | at 8 weeks | Percentage of tissue oxygen saturation (SatO2) will be measured using a validated near-infrared (NIR) camera (Snapshot NIR, KENT Imaging Inc., Calgary, AB, Can) that detects an approximate value of real-time SatO2 level in superficial tissue. The metatarsus area including the five toes will be traced. |
| Stride Time at 4 Weeks During a Dual Walking Task (Blinded Phase) | at 4 weeks | Stride time will be measured with wearable sensors (LEGSys, BioSensics, MA) during a dual walking task (participants asked to count backwards by two while walking) using normal pace for 30 ft. Stride time is defined as the period elapsed between the first contact of two consecutive footsteps of the same foot expressed in seconds. |
| Sleep Duration at 8 Weeks (Unblinded Phase) | Starting at 4 weeks up to 8 weeks | Daily sleep duration in hours obtained with the mean 90 percentile will be measured starting from 4 weeks up to 8 weeks using a smart watch (Vivosmart 4, Garmin, US) |
| Sural Nerve Amplitude at 8 Weeks (Unblinded Phase) | up to 8 weeks | Sural nerve amplitude will be assessed with a DPN Check device (Neurometrix Inc, MA). The device elicits a electrical stimulation upon contact with the skin on the ankle area and returns values that can range from a minimum of 0 microVolts to a maximum of 32 microVolts. Measurements will be obtained at 8 weeks. |
| Double Support Phase at 4 Weeks During a Dual Walking Task (Blinded Phase) | at 4 weeks | Double Support Phase will be measured with wearable sensors (LEGSys, BioSensics, MA) during a dual walking task (participants asked to count backwards by two while walking) using normal pace for 30 ft. Double support phase is defined as percentage time when both feet are simultaneously in contact with the ground during a single stride. |
| Double Support Phase at 4 Weeks During a Fast Walking Task (Blinded Phase) | at 4 weeks | Double Support Phase will be measured with wearable sensors (LEGSys, BioSensics, MA) during a fast walking task (participants asked to walk at a slightly faster pace) for 30 ft. Double support phase is defined as percentage time when both feet are simultaneously in contact with the ground during a single stride. |
| Double Support Phase at 8 Weeks During a Simple Walking Task (Unblinded Phase) | at 8 weeks | Double Support Phase will be measured with wearable sensors (LEGSys, BioSensics, MA) during a free walking task (single task) using normal pace for 30 ft. Double support phase is defined as percentage time when both feet are simultaneously in contact with the ground during a single stride. |
| Double Support Phase at 8 Weeks During a Dual Task (Unblinded Phase) | at 8 weeks | Double Support Phase will be measured with wearable sensors (LEGSys, BioSensics, MA) during a dual walking task (participants asked to count backwards by two while walking) using normal pace for 30 ft. Double support phase is defined as percentage time when both feet are simultaneously in contact with the ground during a single stride. |
| Stride Time at 8 Weeks During a Dual Task (Unblinded Phase) | at 8 weeks | Stride time will be measured with wearable sensors (LEGSys, BioSensics, MA) during a dual walking task (participants asked to count backwards by two while walking) using normal pace for 30 ft. Stride time is defined as the period elapsed between the first contact of two consecutive footsteps of the same foot expressed in seconds. |
| Stride Time at 8 Weeks During a Fast Walk Task (Unblinded Phase) | at 8 weeks | Stride time will be measured with wearable sensors (LEGSys, BioSensics, MA) during a fast walking task (participants asked to walk at a slightly faster pace) for 30 ft. Stride time is defined as the period elapsed between the first contact of two consecutive footsteps of the same foot expressed in seconds. |
| Cadence at 8 Weeks During a Simple Walking Task (Unblinded Phase) | at 8 weeks | Cadence will be measured with wearable sensors (LEGSys, BioSensics, MA) during a free walking task (single task) using normal pace for 30 ft. Cadence is defined as rate of number of steps per minute. |
| Cadence at 8 Weeks During a Dual Task (Unblinded Phase) | at 8 weeks | Cadence will be measured with wearable sensors (LEGSys, BioSensics, MA) during a dual walking task (participants asked to count backwards by two while walking) using normal pace for 30 ft. Cadence is defined as rate of number of steps per minute. |
| Cadence at 8 Weeks During a Fast Walking Task (Unblinded Phase) | at 8 weeks | Cadence will be measured with wearable sensors (LEGSys, BioSensics, MA) during a fast walking task (participants asked to walk at a slightly faster pace) for 30 ft. Cadence is defined as rate of number of steps per minute. |
| Mean Daily Step Count at 8 Weeks (Unblinded Phase) | Starting at 4 weeks up to 8 weeks | Step count obtained with the mean 90 percentile will be will be measured starting from 4 weeks up to 8 weeks using a smart watch (Vivosmart 4, Garmin, US) |
| Stride Time at 4 Weeks During a Fast Walking Task (Blinded Phase) | at 4 weeks | Stride time will be measured with wearable sensors (LEGSys, BioSensics, MA) during a fast walking task (participants asked to walk at a slightly faster pace) for 30 ft. Stride time is defined as the period elapsed between the first contact of two consecutive footsteps of the same foot expressed in seconds. |
| Gastrocnemius Muscle Endurance (Muscle Sustained Contraction) in Response to Electrical Stimulation at 4 Weeks (Blinded Phase) | at 4 weeks | Gastrocnemius muscle endurance in response to 5 minutes of electrical stimulation therapy will be assessed with surface electromyography using a validated non-invasive device (Delsys Trino Wireless EMG System, MA, US). |
| Frailty at 4 Weeks (Blinded Phase) | up to 4 weeks | Frailty will be measured with a upper-extremity wearable sensor (Frailty meter, BioSensics, MA) which enables a frailty index score based on a validated algorithm. Patients with frailty index \>0.27 is considered are considered as frail. Patients with a frailty index \<0.27 are considered as non-frail. The higher the frailty index, the higher the level of frailty. The frailty index ranges from 0-1. |
| Sural Nerve Conduction Velocity at 4 Weeks (Blinded Phase) | 4 weeks | Sural nerve conduction will be assessed with a DPN Check device (Neurometrix Inc, MA). The device elicits a electrical stimulation upon contact with the skin on the ankle area and returns values that can range from a minimum of 20 m/s to a maximum of 60m/s. Measurements will be obtained at 4 weeks and value will be compared between groups. |
| Ankle Strength at 4 Weeks (Blinded Phase) | up to 4 weeks | Ankle strength will be assessed with an ankle dynamometer. Participants will be asked to perform 3 maximum voluntary contractions (MVC) sustaining ankle dorsiflexion for 5 seconds with 30 seconds of resting in between MVCs. The average of the 3 MVCs will then be calculated per lower extremity. |
| Plantar Tissue Oxygen Saturation at 4 Weeks (Blinded Phase) | up to 4 weeks | Percentage of tissue oxygen saturation (SatO2) will be measured using a validated near-infrared (NIR) camera (Snapshot NIR, KENT Imaging Inc., Calgary, AB, Can) that detects an approximate value of real-time SatO2 level in superficial tissue. The metatarsus area including the five toes will be traced. |
| Mean Daily Step Count at 4 Weeks (Blinded Phase) | up to 4 weeks | Step count obtained with the mean 90 percentile will be will be measured over the course of the 4 weeks using a smart watch (Vivosmart 4, Garmin, US) |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Group (PG) Placebo Group (PG) The PG (n=15) will be undergoing TENS therapy with a sham device as described in the AG. The sham device is identical to the active device in all respects except that it stimulates for 6 minutes during each therapy session instead of 60 minutes, and is therefore 10% of the dose.
Electrical Stimulation - Placebo: Subjects will receive a placebo electrical stimulation device (delivers 10% of the dose) to wear for 1 hour daily for up to 4 weeks. | 13 |
| Active Group (AG) Active group (AG). The AG (n=15) will be undergoing TENS therapy with an active device during 4 weeks. To deliver TENS, a band strap with hydrogel pads will be placed around the calf muscle of one lower-extremity alternating to the other side in a weekly basis.
Electrical Stimulation - Active: Subjects will receive an active electrical stimulation device (delivers 100% of the dose) to wear for 1 hour daily for up to 4 weeks. | 12 |
| Total | 25 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Blinded Phase (4 Weeks) | Lost to Follow-up | 3 | 2 | 0 | 0 |
Baseline characteristics
| Characteristic | Active Group (AG) | Total | Placebo Group (PG) |
|---|---|---|---|
| Age, Continuous | 51.08 years STANDARD_DEVIATION 12.32 | 45.28 years STANDARD_DEVIATION 12.18 | 43.38 years STANDARD_DEVIATION 11.79 |
| Body Mass Index (BMI) | 27.72 kg/m^2 STANDARD_DEVIATION 7.92 | 27.74 kg/m^2 STANDARD_DEVIATION 6.95 | 27.76 kg/m^2 STANDARD_DEVIATION 5.98 |
| High Blood Pressure | 2 Participants | 5 Participants | 3 Participants |
| Race/Ethnicity, Customized Asian | 0 Participants | 2 Participants | 2 Participants |
| Race/Ethnicity, Customized Black | 2 Participants | 3 Participants | 1 Participants |
| Race/Ethnicity, Customized Hispanic | 3 Participants | 5 Participants | 2 Participants |
| Race/Ethnicity, Customized Unknown | 1 Participants | 3 Participants | 2 Participants |
| Race/Ethnicity, Customized White | 6 Participants | 12 Participants | 6 Participants |
| Region of Enrollment United States | 12 participants | 25 participants | 13 participants |
| Sex: Female, Male Female | 10 Participants | 19 Participants | 9 Participants |
| Sex: Female, Male Male | 2 Participants | 6 Participants | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 15 | 0 / 15 | 0 / 12 | 0 / 13 |
| other Total, other adverse events | 3 / 15 | 3 / 15 | 0 / 12 | 0 / 13 |
| serious Total, serious adverse events | 0 / 15 | 0 / 15 | 0 / 12 | 0 / 13 |
Outcome results
Primary
Mean Change in Functional Interference From Pain From Baseline to 4 Weeks (Blinded Phase)
Pain will be assessed with a validated questionnaire called Brief Pain Inventory interference composite score (BPI-I). The maximum score is 10, meaning pain completely interferes, while the minimum score is zero, meaning pain does not interfere.
Time frame: baseline to 4 weeks
Population: Blinded phase of the study at 4 weeks.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intervention Group | Mean Change in Functional Interference From Pain From Baseline to 4 Weeks (Blinded Phase) | 0.454 score on a scale | Standard Error 0.503 |
| Placebo Group | Mean Change in Functional Interference From Pain From Baseline to 4 Weeks (Blinded Phase) | 0.198 score on a scale | Standard Error 0.503 |
Secondary
Cadence at 4 Weeks During a Dual Walking Task (Blinded Phase)
Cadence will be measured with wearable sensors (LEGSys, BioSensics, MA) during a dual walking task (participants asked to count backwards by two while walking) using normal pace for 30 ft. Cadence is defined as rate of number of steps per minute.
Time frame: at 4 weeks
Population: blinded phase
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intervention Group | Cadence at 4 Weeks During a Dual Walking Task (Blinded Phase) | 103.40 steps/min | Standard Deviation 17.36 |
| Placebo Group | Cadence at 4 Weeks During a Dual Walking Task (Blinded Phase) | 103.40 steps/min | Standard Deviation 14.84 |
Secondary
Cadence at 4 Weeks During a Fast Walking Task (Blinded Phase)
Cadence will be measured with wearable sensors (LEGSys, BioSensics, MA) during a fast walking task (participants asked to walk at a slightly faster pace) for 30 ft. Cadence is defined as rate of number of steps per minute.
Time frame: at 4 weeks
Population: blinded phase
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intervention Group | Cadence at 4 Weeks During a Fast Walking Task (Blinded Phase) | 122.57 steps/min | Standard Deviation 15.87 |
| Placebo Group | Cadence at 4 Weeks During a Fast Walking Task (Blinded Phase) | 122.57 steps/min | Standard Deviation 14.8 |
Secondary
Cadence at 4 Weeks During a Simple Walking Task (Blinded Phase)
Cadence will be measured with wearable sensors (LEGSys, BioSensics, MA) during a free walking task (single task) using normal pace for 30 ft. Cadence is defined as rate of number of steps per minute.
Time frame: at 4 weeks
Population: blinded phase
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intervention Group | Cadence at 4 Weeks During a Simple Walking Task (Blinded Phase) | 106.42 steps/min | Standard Deviation 10.35 |
| Placebo Group | Cadence at 4 Weeks During a Simple Walking Task (Blinded Phase) | 105.90 steps/min | Standard Deviation 10.13 |
Secondary
Double Support Phase at 4 Weeks During a Simple Walking Task (Blinded Phase)
Double Support Phase will be measured with wearable sensors (LEGSys, BioSensics, MA) during a free walking task (single task) using normal pace for 30 ft. Double support phase is defined as percentage time when both feet are simultaneously in contact with the ground during a single stride.
Time frame: at 4 weeks
Population: blinded phase
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intervention Group | Double Support Phase at 4 Weeks During a Simple Walking Task (Blinded Phase) | 22.84 percentage of time | Standard Deviation 3.98 |
| Placebo Group | Double Support Phase at 4 Weeks During a Simple Walking Task (Blinded Phase) | 22.64 percentage of time | Standard Deviation 4.08 |
Secondary
Mean Change in Functional Interference From Fatigue From Baseline to 4 Weeks (Blinded Phase)
Functional interference from fatigue will be assessed calculating the Global Fatigue Index (GFI) obtained from a validated questionnaire called Multidimensional Assessment Fatigue, which has a minimum score of 0 (no fatigue) and a maximum sore of 100 (severe fatigue).
Time frame: Baseline to 4 weeks
Population: Blinded phase of the study.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intervention Group | Mean Change in Functional Interference From Fatigue From Baseline to 4 Weeks (Blinded Phase) | 2.821 score on a scale | Standard Error 1.504 |
| Placebo Group | Mean Change in Functional Interference From Fatigue From Baseline to 4 Weeks (Blinded Phase) | 2.231 score on a scale | Standard Error 3.207 |
Secondary
Mean Change in Pain Severity From Baseline to 4 Weeks (Blinded Phase)
Pain severity will be assessed using the Brief Pain Inventory questionnaire composite score for severity. The maximum score is 10, meaning pain as bad as one can imagine, while the minimum score is zero, meaning no pain.
Time frame: Baseline to 4 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intervention Group | Mean Change in Pain Severity From Baseline to 4 Weeks (Blinded Phase) | 1.184 score on a scale | Standard Error 0.815 |
| Placebo Group | Mean Change in Pain Severity From Baseline to 4 Weeks (Blinded Phase) | 0.289 score on a scale | Standard Error 0.255 |
Secondary
Stride Time at 4 Weeks During a Simple Walking Task (Blinded Phase)
Stride time will be measured with wearable sensors (LEGSys, BioSensics, MA) during a free walking task (single task) using normal pace for 30 ft. Stride time is defined as the period elapsed between the first contact of two consecutive footsteps of the same foot expressed in seconds.
Time frame: at 4 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intervention Group | Stride Time at 4 Weeks During a Simple Walking Task (Blinded Phase) | 1.13 seconds | Standard Deviation 0.03 |
| Placebo Group | Stride Time at 4 Weeks During a Simple Walking Task (Blinded Phase) | 1.16 seconds | Standard Deviation 0.03 |
Other Pre-specified
Ankle Strength at 4 Weeks (Blinded Phase)
Ankle strength will be assessed with an ankle dynamometer. Participants will be asked to perform 3 maximum voluntary contractions (MVC) sustaining ankle dorsiflexion for 5 seconds with 30 seconds of resting in between MVCs. The average of the 3 MVCs will then be calculated per lower extremity.
Time frame: up to 4 weeks
Population: bilateral ankle strength was measured in each participant
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intervention Group | Ankle Strength at 4 Weeks (Blinded Phase) | 7.78 kg | Standard Deviation 0.82 |
| Placebo Group | Ankle Strength at 4 Weeks (Blinded Phase) | 7.93 kg | Standard Deviation 1.09 |
Other Pre-specified
Ankle Strength at 8 Weeks (Unblinded Phase)
Ankle strength will be assessed with an ankle dynamometer. Participants will be asked to perform 3 maximum voluntary contractions (MVC) sustaining ankle dorsiflexion for 5 seconds with 30 seconds of resting in between MVCs. The average of the 3 MVCs will then be calculated per lower extremity.
Time frame: at 8 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intervention Group | Ankle Strength at 8 Weeks (Unblinded Phase) | 9.59 kg | Standard Deviation 5.11 |
| Placebo Group | Ankle Strength at 8 Weeks (Unblinded Phase) | 9.79 kg | Standard Deviation 5.18 |
Other Pre-specified
Cadence at 8 Weeks During a Dual Task (Unblinded Phase)
Cadence will be measured with wearable sensors (LEGSys, BioSensics, MA) during a dual walking task (participants asked to count backwards by two while walking) using normal pace for 30 ft. Cadence is defined as rate of number of steps per minute.
Time frame: at 8 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intervention Group | Cadence at 8 Weeks During a Dual Task (Unblinded Phase) | 100.51 steps/min | Standard Deviation 12.56 |
| Placebo Group | Cadence at 8 Weeks During a Dual Task (Unblinded Phase) | 96.04 steps/min | Standard Deviation 10.62 |
Other Pre-specified
Cadence at 8 Weeks During a Fast Walking Task (Unblinded Phase)
Cadence will be measured with wearable sensors (LEGSys, BioSensics, MA) during a fast walking task (participants asked to walk at a slightly faster pace) for 30 ft. Cadence is defined as rate of number of steps per minute.
Time frame: at 8 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intervention Group | Cadence at 8 Weeks During a Fast Walking Task (Unblinded Phase) | 122.80 steps/min | Standard Deviation 14.88 |
| Placebo Group | Cadence at 8 Weeks During a Fast Walking Task (Unblinded Phase) | 116.14 steps/min | Standard Deviation 12.59 |
Other Pre-specified
Cadence at 8 Weeks During a Simple Walking Task (Unblinded Phase)
Cadence will be measured with wearable sensors (LEGSys, BioSensics, MA) during a free walking task (single task) using normal pace for 30 ft. Cadence is defined as rate of number of steps per minute.
Time frame: at 8 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intervention Group | Cadence at 8 Weeks During a Simple Walking Task (Unblinded Phase) | 105.36 steps/min | Standard Deviation 10.16 |
| Placebo Group | Cadence at 8 Weeks During a Simple Walking Task (Unblinded Phase) | 101.63 steps/min | Standard Deviation 5.77 |
Other Pre-specified
Double Support Phase at 4 Weeks During a Dual Walking Task (Blinded Phase)
Double Support Phase will be measured with wearable sensors (LEGSys, BioSensics, MA) during a dual walking task (participants asked to count backwards by two while walking) using normal pace for 30 ft. Double support phase is defined as percentage time when both feet are simultaneously in contact with the ground during a single stride.
Time frame: at 4 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intervention Group | Double Support Phase at 4 Weeks During a Dual Walking Task (Blinded Phase) | 24.45 percentage time | Standard Deviation 8.47 |
| Placebo Group | Double Support Phase at 4 Weeks During a Dual Walking Task (Blinded Phase) | 24.45 percentage time | Standard Deviation 8.81 |
Other Pre-specified
Double Support Phase at 4 Weeks During a Fast Walking Task (Blinded Phase)
Double Support Phase will be measured with wearable sensors (LEGSys, BioSensics, MA) during a fast walking task (participants asked to walk at a slightly faster pace) for 30 ft. Double support phase is defined as percentage time when both feet are simultaneously in contact with the ground during a single stride.
Time frame: at 4 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intervention Group | Double Support Phase at 4 Weeks During a Fast Walking Task (Blinded Phase) | 17.87 percentage time | Standard Deviation 4.63 |
| Placebo Group | Double Support Phase at 4 Weeks During a Fast Walking Task (Blinded Phase) | 17.87 percentage time | Standard Deviation 4.57 |
Other Pre-specified
Double Support Phase at 8 Weeks During a Dual Task (Unblinded Phase)
Double Support Phase will be measured with wearable sensors (LEGSys, BioSensics, MA) during a dual walking task (participants asked to count backwards by two while walking) using normal pace for 30 ft. Double support phase is defined as percentage time when both feet are simultaneously in contact with the ground during a single stride.
Time frame: at 8 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intervention Group | Double Support Phase at 8 Weeks During a Dual Task (Unblinded Phase) | 24.47 percentage | Standard Deviation 3.24 |
| Placebo Group | Double Support Phase at 8 Weeks During a Dual Task (Unblinded Phase) | 24.51 percentage | Standard Deviation 2.27 |
Other Pre-specified
Double Support Phase at 8 Weeks During a Simple Walking Task (Unblinded Phase)
Double Support Phase will be measured with wearable sensors (LEGSys, BioSensics, MA) during a free walking task (single task) using normal pace for 30 ft. Double support phase is defined as percentage time when both feet are simultaneously in contact with the ground during a single stride.
Time frame: at 8 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intervention Group | Double Support Phase at 8 Weeks During a Simple Walking Task (Unblinded Phase) | 20.69 percentage time | Standard Deviation 4.77 |
| Placebo Group | Double Support Phase at 8 Weeks During a Simple Walking Task (Unblinded Phase) | 21.75 percentage time | Standard Deviation 4.13 |
Other Pre-specified
Frailty at 4 Weeks (Blinded Phase)
Frailty will be measured with a upper-extremity wearable sensor (Frailty meter, BioSensics, MA) which enables a frailty index score based on a validated algorithm. Patients with frailty index \>0.27 is considered are considered as frail. Patients with a frailty index \<0.27 are considered as non-frail. The higher the frailty index, the higher the level of frailty. The frailty index ranges from 0-1.
Time frame: up to 4 weeks
Population: blinded phase of study
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intervention Group | Frailty at 4 Weeks (Blinded Phase) | 0.18 frailty index | Standard Deviation 0.04 |
| Placebo Group | Frailty at 4 Weeks (Blinded Phase) | 0.21 frailty index | Standard Deviation 0.05 |
Other Pre-specified
Frailty at 8 Weeks (Unblinded Phase)
Frailty will be measured with an upper-extremity wearable sensor (Frailty meter, BioSensics, MA) which enables a frailty index score based on a validated algorithm. Patients with frailty index \>0.27 is considered are considered as frail. Patients with a frailty index \<0.27 are considered as non-frail. The higher the frailty index, the higher the level of frailty. The frailty index ranges from 0-1.
Time frame: at 8 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intervention Group | Frailty at 8 Weeks (Unblinded Phase) | 0.19 frailty index | Standard Deviation 0.07 |
| Placebo Group | Frailty at 8 Weeks (Unblinded Phase) | 0.19 frailty index | Standard Deviation 0.07 |
Other Pre-specified
Gastrocnemius Muscle Endurance (Muscle Sustained Contraction) in Response to Electrical Stimulation at 4 Weeks (Blinded Phase)
Gastrocnemius muscle endurance in response to 5 minutes of electrical stimulation therapy will be assessed with surface electromyography using a validated non-invasive device (Delsys Trino Wireless EMG System, MA, US).
Time frame: at 4 weeks
Population: Blinded phase of study
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intervention Group | Gastrocnemius Muscle Endurance (Muscle Sustained Contraction) in Response to Electrical Stimulation at 4 Weeks (Blinded Phase) | 150.93 Hertz | Standard Deviation 7.44 |
| Placebo Group | Gastrocnemius Muscle Endurance (Muscle Sustained Contraction) in Response to Electrical Stimulation at 4 Weeks (Blinded Phase) | 154.44 Hertz | Standard Deviation 8.07 |
Other Pre-specified
Gastrocnemius Muscle Endurance (Muscle Sustained Contraction) in Response to Electrical Stimulation at 8 Weeks (Unblinded Phase)
Gastrocnemius muscle endurance in response to 5 minutes of electrical stimulation therapy will be assessed with surface electromyography using a validated non-invasive device (Delsys Trino Wireless EMG System, MA, US).
Time frame: at 8 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intervention Group | Gastrocnemius Muscle Endurance (Muscle Sustained Contraction) in Response to Electrical Stimulation at 8 Weeks (Unblinded Phase) | 148.90 Hertz | Standard Deviation 6.6 |
| Placebo Group | Gastrocnemius Muscle Endurance (Muscle Sustained Contraction) in Response to Electrical Stimulation at 8 Weeks (Unblinded Phase) | 148.52 Hertz | Standard Deviation 6.09 |
Other Pre-specified
Mean Change in Functional Interference From Fatigue From 4 Weeks to 8 Weeks (Unblinded Phase)
Functional interference from fatigue will be assessed calculating the Global Fatigue Index (GFI) obtained from a validated questionnaire called Multidimensional Assessment Fatigue, which has a minimum score of 0 (no fatigue) and a maximum sore of 100 (severe fatigue). This outcome assesses the difference between the mean global fatigue index at week 8 and week 4.
Time frame: 4 weeks to 8 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intervention Group | Mean Change in Functional Interference From Fatigue From 4 Weeks to 8 Weeks (Unblinded Phase) | -0.39 score on a scale | Standard Deviation 7.91 |
| Placebo Group | Mean Change in Functional Interference From Fatigue From 4 Weeks to 8 Weeks (Unblinded Phase) | 2.14 score on a scale | Standard Deviation 5.88 |
Other Pre-specified
Mean Change in Functional Interference From Pain at 8 Weeks (Unblinded Phase)
Pain will be assessed with a validated questionnaire called Brief Pain Inventory interference composite score (BPI-I). The maximum score is 10, meaning pain completely interferes, while the minimum score is zero, meaning pain does not interfere. This outcome assesses the difference between the mean BPI interference composite score at week 8 and week 4.
Time frame: from week 4 to week 8
Population: week 4 to week 8
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intervention Group | Mean Change in Functional Interference From Pain at 8 Weeks (Unblinded Phase) | 0.29 score on a scale | Standard Deviation 2.03 |
| Placebo Group | Mean Change in Functional Interference From Pain at 8 Weeks (Unblinded Phase) | -0.87 score on a scale | Standard Deviation 1.27 |
Other Pre-specified
Mean Change in Pain Severity From 4 Weeks to 8 Weeks (Unblinded Phase)
Pain severity will be assessed using the Brief Pain Inventory questionnaire composite score for severity. The maximum score is 10, meaning pain as bad as one can imagine, while the minimum score is zero, meaning no pain. This outcome assesses the difference between the mean BPI severity composite score at week 8 and week 4.
Time frame: 4 weeks to 8 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intervention Group | Mean Change in Pain Severity From 4 Weeks to 8 Weeks (Unblinded Phase) | 0.53 score on a scale | Standard Deviation 1.09 |
| Placebo Group | Mean Change in Pain Severity From 4 Weeks to 8 Weeks (Unblinded Phase) | -0.43 score on a scale | Standard Deviation 1.24 |
Other Pre-specified
Mean Daily Step Count at 4 Weeks (Blinded Phase)
Step count obtained with the mean 90 percentile will be will be measured over the course of the 4 weeks using a smart watch (Vivosmart 4, Garmin, US)
Time frame: up to 4 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intervention Group | Mean Daily Step Count at 4 Weeks (Blinded Phase) | 4988.11 steps/day | Standard Deviation 3396.2 |
| Placebo Group | Mean Daily Step Count at 4 Weeks (Blinded Phase) | 4887.59 steps/day | Standard Deviation 3594.3 |
Other Pre-specified
Mean Daily Step Count at 8 Weeks (Unblinded Phase)
Step count obtained with the mean 90 percentile will be will be measured starting from 4 weeks up to 8 weeks using a smart watch (Vivosmart 4, Garmin, US)
Time frame: Starting at 4 weeks up to 8 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intervention Group | Mean Daily Step Count at 8 Weeks (Unblinded Phase) | 3545.86 steps/day | Standard Deviation 4569.65 |
| Placebo Group | Mean Daily Step Count at 8 Weeks (Unblinded Phase) | 4166.31 steps/day | Standard Deviation 3897.13 |
Other Pre-specified
Plantar Tissue Oxygen Saturation at 4 Weeks (Blinded Phase)
Percentage of tissue oxygen saturation (SatO2) will be measured using a validated near-infrared (NIR) camera (Snapshot NIR, KENT Imaging Inc., Calgary, AB, Can) that detects an approximate value of real-time SatO2 level in superficial tissue. The metatarsus area including the five toes will be traced.
Time frame: up to 4 weeks
Population: blinded phase of study
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intervention Group | Plantar Tissue Oxygen Saturation at 4 Weeks (Blinded Phase) | 67.46 percentage of oxygen saturation | Standard Deviation 0.78 |
| Placebo Group | Plantar Tissue Oxygen Saturation at 4 Weeks (Blinded Phase) | 66.31 percentage of oxygen saturation | Standard Deviation 0.62 |
Other Pre-specified
Plantar Tissue Oxygen Saturation at 8 Weeks (Unblinded Phase)
Percentage of tissue oxygen saturation (SatO2) will be measured using a validated near-infrared (NIR) camera (Snapshot NIR, KENT Imaging Inc., Calgary, AB, Can) that detects an approximate value of real-time SatO2 level in superficial tissue. The metatarsus area including the five toes will be traced.
Time frame: at 8 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intervention Group | Plantar Tissue Oxygen Saturation at 8 Weeks (Unblinded Phase) | 67.82 percentage of oxygen saturation | Standard Deviation 3.79 |
| Placebo Group | Plantar Tissue Oxygen Saturation at 8 Weeks (Unblinded Phase) | 67.38 percentage of oxygen saturation | Standard Deviation 3.38 |
Other Pre-specified
Sleep Duration at 4 Weeks (Blinded Phase)
Daily sleep duration in hours obtained with the mean 90 percentile will be measured over the course of the 4 weeks using a smart watch (Vivosmart 4, Garmin, US)
Time frame: up to 4 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intervention Group | Sleep Duration at 4 Weeks (Blinded Phase) | 9.2 hours/day | Standard Deviation 1.39 |
| Placebo Group | Sleep Duration at 4 Weeks (Blinded Phase) | 9.3 hours/day | Standard Deviation 1.2 |
Other Pre-specified
Sleep Duration at 8 Weeks (Unblinded Phase)
Daily sleep duration in hours obtained with the mean 90 percentile will be measured starting from 4 weeks up to 8 weeks using a smart watch (Vivosmart 4, Garmin, US)
Time frame: Starting at 4 weeks up to 8 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intervention Group | Sleep Duration at 8 Weeks (Unblinded Phase) | 2.64 hours/day | Standard Deviation 1.83 |
| Placebo Group | Sleep Duration at 8 Weeks (Unblinded Phase) | 10.53 hours/day | Standard Deviation 2.4 |
Other Pre-specified
Stride Time at 4 Weeks During a Dual Walking Task (Blinded Phase)
Stride time will be measured with wearable sensors (LEGSys, BioSensics, MA) during a dual walking task (participants asked to count backwards by two while walking) using normal pace for 30 ft. Stride time is defined as the period elapsed between the first contact of two consecutive footsteps of the same foot expressed in seconds.
Time frame: at 4 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intervention Group | Stride Time at 4 Weeks During a Dual Walking Task (Blinded Phase) | 1.19 seconds | Standard Deviation 0.21 |
| Placebo Group | Stride Time at 4 Weeks During a Dual Walking Task (Blinded Phase) | 1.19 seconds | Standard Deviation 0.2 |
Other Pre-specified
Stride Time at 4 Weeks During a Fast Walking Task (Blinded Phase)
Stride time will be measured with wearable sensors (LEGSys, BioSensics, MA) during a fast walking task (participants asked to walk at a slightly faster pace) for 30 ft. Stride time is defined as the period elapsed between the first contact of two consecutive footsteps of the same foot expressed in seconds.
Time frame: at 4 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intervention Group | Stride Time at 4 Weeks During a Fast Walking Task (Blinded Phase) | 1.00 seconds | Standard Deviation 0.13 |
| Placebo Group | Stride Time at 4 Weeks During a Fast Walking Task (Blinded Phase) | 1.00 seconds | Standard Deviation 0.12 |
Other Pre-specified
Stride Time at 8 Weeks During a Dual Task (Unblinded Phase)
Stride time will be measured with wearable sensors (LEGSys, BioSensics, MA) during a dual walking task (participants asked to count backwards by two while walking) using normal pace for 30 ft. Stride time is defined as the period elapsed between the first contact of two consecutive footsteps of the same foot expressed in seconds.
Time frame: at 8 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intervention Group | Stride Time at 8 Weeks During a Dual Task (Unblinded Phase) | 1.21 seconds | Standard Deviation 0.15 |
| Placebo Group | Stride Time at 8 Weeks During a Dual Task (Unblinded Phase) | 1.27 seconds | Standard Deviation 0.15 |
Other Pre-specified
Stride Time at 8 Weeks During a Fast Walk Task (Unblinded Phase)
Stride time will be measured with wearable sensors (LEGSys, BioSensics, MA) during a fast walking task (participants asked to walk at a slightly faster pace) for 30 ft. Stride time is defined as the period elapsed between the first contact of two consecutive footsteps of the same foot expressed in seconds.
Time frame: at 8 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intervention Group | Stride Time at 8 Weeks During a Fast Walk Task (Unblinded Phase) | 0.99 seconds | Standard Deviation 0.11 |
| Placebo Group | Stride Time at 8 Weeks During a Fast Walk Task (Unblinded Phase) | 1.04 seconds | Standard Deviation 0.1 |
Other Pre-specified
Stride Time at 8 Weeks During a Simple Walking Task (Unblinded Phase)
Stride time will be measured with wearable sensors (LEGSys, BioSensics, MA) during a free walking task (single task) using normal pace for 30 ft. Stride time is defined as the period elapsed between the first contact of two consecutive footsteps of the same foot expressed in seconds.
Time frame: at 8 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intervention Group | Stride Time at 8 Weeks During a Simple Walking Task (Unblinded Phase) | 1.15 seconds | Standard Deviation 0.1 |
| Placebo Group | Stride Time at 8 Weeks During a Simple Walking Task (Unblinded Phase) | 1.16 seconds | Standard Deviation 0.1 |
Other Pre-specified
Sural Nerve Amplitude at 4 Weeks (Blinded Phase)
Sural nerve amplitude will be assessed with a DPN Check device (Neurometrix Inc, MA). The device elicits a electrical stimulation upon contact with the skin on the ankle area and returns values that can range from a minimum of 0 microVolts to a maximum of 32 microVolts. Measurements will be obtained at 4 weeks.
Time frame: at 4 weeks
Population: Sural nerve amplitude will be measured in each of the participant's legs
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intervention Group | Sural Nerve Amplitude at 4 Weeks (Blinded Phase) | 14.4 microVolts | Standard Deviation 6.23 |
| Placebo Group | Sural Nerve Amplitude at 4 Weeks (Blinded Phase) | 16.04 microVolts | Standard Deviation 12.1 |
Other Pre-specified
Sural Nerve Amplitude at 8 Weeks (Unblinded Phase)
Sural nerve amplitude will be assessed with a DPN Check device (Neurometrix Inc, MA). The device elicits a electrical stimulation upon contact with the skin on the ankle area and returns values that can range from a minimum of 0 microVolts to a maximum of 32 microVolts. Measurements will be obtained at 8 weeks.
Time frame: up to 8 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intervention Group | Sural Nerve Amplitude at 8 Weeks (Unblinded Phase) | 14.71 microVolts | Standard Deviation 7.47 |
| Placebo Group | Sural Nerve Amplitude at 8 Weeks (Unblinded Phase) | 14.71 microVolts | Standard Deviation 6.99 |
Other Pre-specified
Sural Nerve Conduction Velocity at 4 Weeks (Blinded Phase)
Sural nerve conduction will be assessed with a DPN Check device (Neurometrix Inc, MA). The device elicits a electrical stimulation upon contact with the skin on the ankle area and returns values that can range from a minimum of 20 m/s to a maximum of 60m/s. Measurements will be obtained at 4 weeks and value will be compared between groups.
Time frame: 4 weeks
Population: Sural nerve conduction velocity from both right and left lower extremities were measured in each participant
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intervention Group | Sural Nerve Conduction Velocity at 4 Weeks (Blinded Phase) | 54.96 m/s | Standard Deviation 1.16 |
| Placebo Group | Sural Nerve Conduction Velocity at 4 Weeks (Blinded Phase) | 55.96 m/s | Standard Deviation 1.4 |
Other Pre-specified
Sural Nerve Conduction Velocity at 8 Weeks (Unblinded Phase)
Sural nerve conduction will be assessed with a DPN Check device (Neurometrix Inc, MA). The device elicits a electrical stimulation upon contact with the skin on the ankle area and returns values that can range from a minimum of 20 m/s to a maximum of 60m/s. Measurements will be obtained at 8 weeks and value will be compared between groups.
Time frame: at 8 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intervention Group | Sural Nerve Conduction Velocity at 8 Weeks (Unblinded Phase) | 55.64 m/s | Standard Deviation 5.02 |
| Placebo Group | Sural Nerve Conduction Velocity at 8 Weeks (Unblinded Phase) | 56.04 m/s | Standard Deviation 5.02 |