Diabetic Neuropathy Peripheral
Conditions
Brief summary
Part A of this trial is a multi-center, prospective, double-blinded, sham-controlled, randomized clinical trial. Part A will evaluate PEMF treatment compared to sham treatment in patients with painful diabetic distal symmetric peripheral neuropathy (DSPN) when treatment is administered 30 minutes twice daily through a 120-day period (4 months). Part B is a 8-month open-label active treatment extension period designed to collect longer-term data on pain, medication use, quality of life and safety (Part B).Part B of this trial is a an extension period upon completion of Part A.
Detailed description
Eligible subjects will be entered into a 14-day ePRO diary run-in period to collect average baseline pain scores related to their diabetic neuropathy in the lower extremities, diary compliance, and analgesic consumption (maintenance and prn prescribed peripheral neuropathic pain medication pill counts). Subjects will collect electronic patient-reported outcome (ePRO) data each morning around the same time during the run-in period. Subjects will return to the clinic at Baseline (Day 0) for review of eligibility, diary compliance, average baseline diabetic neuropathic pain score of ≥4 and \<9, and review of stable analgesic pain consumption profile during the 14-day run-in period. Qualified subjects based on diary compliance and average pain score will be randomized 1:1 (active: sham) and will be instructed to self-treat twice daily for 120 days. Subjects will record electronic patient-reported outcome (ePRO) data following each morning treatment for 120 days. Subjects consenting to distal thigh and distal leg skin biopsies during the Screening visit will have biopsies collected and sent to the central laboratory for assessment. All subjects will have baseline assessments conducted. Subjects will receive a telephone call at Day 7 to ensure compliance to treatment and diary completion, provide follow-up information on the biopsy sites (if applicable), complete a blinding assessment as well as be assessed for safety and concomitant medication changes. At Month 1 subjects will return to the clinic for evaluation of safety, concomitant medication changes, review device usage and ePRO diary completion, and Patient Global Impression (PGI). Treatment satisfaction will also be assessed. At Month 2 subjects will return to the clinic for evaluation of safety, concomitant medication changes, treatment satisfaction, review of device usage (reports will be supplied to the site) and ePRO diary completion, quality of life outcomes (WPAIQ and NeuroQoL), Patient Global Impression (PGI), and interim visit measurements of SPP. At Month 3, subjects will return to the clinic for evaluation of safety, concomitant medication changes, review device usage (reports will be supplied to the site) and ePRO diary completion, and Patient Global Impression (PGI). Treatment satisfaction will also be assessed. At Month 4 (end of Part A / start of Part B), subjects will return to the clinic for evaluation of safety, treatment satisfaction, review of device usage (reports will be supplied to the site), HbA1c, concomitant medication changes, weight, quality of life outcomes (WPAIQ and NeuroQoL), PGI, final measurements of SPP, NCS, QST and be assessed to determine their Toronto Clinical Neuropathy Score. Those subjects who consented and had biopsies collected at the Enrollment visit, will have their end of study biopsies during this visit and samples sent directly to the central laboratory for assessment. Subjects will return the study device and complete a blinding assessment. Subjects that complete Part A will continue into the open-label extension period (Part B). All subjects will be reconsented if not completed at a prior visit and given an open-label active device. Subjects will record ePRO data for one week prior to the Month 6, 8, 10, and 12 visits following each morning treatment. Subjects will be reminded of the150-day (Month 5) phone call. At Month 5, subjects will receive a telephone call to ensure compliance to treatment, and to be assessed for safety and concomitant medication changes. At Month 6, subjects will receive a telephone call to ensure treatment compliance and collection of diary data, and to assess safety and concomitant medication changes. At Month 7, subjects will receive a telephone call to ensure treatment compliance, and to assess safety and concomitant medication changes. At Month 8, subjects will return to the clinic for evaluation of safety, measure QST, treatment satisfaction, review of device usage and collection of diary data, concomitant medication changes, quality of life outcomes (NeuroQoL), and PGI. At Month 9, subjects will receive a telephone call to ensure treatment compliance, and to assess safety and concomitant medication changes. At Month 10, subjects will receive a telephone call to ensure treatment compliance and collection of diary data, and to assess safety and concomitant medication changes. At Month 11, subjects will receive a telephone call to ensure treatment compliance, and to assess safety and concomitant medication changes. At Month 12 (end of open-label treatment extension), subjects will return to the clinic for evaluation of safety, weight, QST, NCS, TCNSS, PGI, treatment satisfaction, review of device usage and collection of diary data, concomitant medication changes, quality of life outcomes (NeuroQoL), and will return the study device. Subjects who consented and had biopsies collected at the 4 Month visit, will have their end of study biopsies performed during this visit.
Interventions
Treatment with active Provant Therapy System
Treatment with inactive Provant Therapy System
Sponsors
Regenesis Biomedical, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Active and sham devices will look identical. Participants and site staff will be blind to the randomization.
Intervention model description
Two parallel groups, active device group versus sham device group. Subjects will be randomized 1:1 at baseline and treat with active PEMF or sham for 4 months.
Eligibility
Sex/Gender
ALL
Age
22 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Type 1 or Type 2 diabetes * Pain attributed to symmetrical lower extremity diabetic peripheral neuropathy for at least 6 months * DPN pain over the preceding 24 hours is ≥4 and \<9 based on the 11-point NPRS (0-10) * 22 to 80 years of age * On stable diabetes treatment * HbA1c less than or equal to 10% * No recent changes to analgesic prescriptions * ABI of ≥0.8 to ≤1.3 * Walks independently * Willing and able to give consent * If female, must be post-menopausal, surgically sterile, abstinent or practicing an effective method of birth control * Can access an internet browser or smart phone To be randomized after the 14-day run-in period, average pain (NPRS) must be ≥ 4 and \< 9 over preceding 7 days and subject must be 70% compliant with ePRO assessments (electronic diary)
Exclusion criteria
* Active, open ulcer on either extremity * Significant peripheral vascular disease * Venous insufficiency * History of solid organ transplant or severe renal disease * Diagnosed with a non-diabetic cause of chronic neuropathy * Previous or current history of primary or tertiary hyperparathyroidism, hypercalcemia, psychiatric disorder, alcohol dependency, Hepatitis B or C, or HIV infection * Significant cardiovascular disease * Uncontrolled medical illness * Requires or anticipates the need for surgery during the study * Total foot depth of \>8 cm * Has received any investigational drug or device within 30 days * Has used systemic corticosteroids within 3 months * History of malignancy within 5 years in treatment area * A psychiatric disorder of sufficient severity * Receiving prn narcotic medications * History of drug or alcohol abuse within 1 year * Implanted pacemaker, defibrillator, neurostimulator, spinal cord stimulator, bone stimulator, cochlear implant, or other implanted device with an implanted metal lead(s0 * Pregnant or planning to become pregnant * Previous treatment with Provant Therapy * Unwilling to follow instructions or comply with study instructions * Pain from any other source that could confuse DPN pain assessment * Clinically significant foot deformity * Skin condition that could alter peripheral sensations * Previous surgery to the spine or lower extremity with residual symptoms of pain or difficulty with movement. * Clinically significant arthropathy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Pain Intensity | Baseline through 4 months | Absolute change in pain intensity as measured by the 11-point, numerical pain rating scale (NPRS) (0-10; where 0=no pain, to 10=worst possible pain). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Patients With 2 Point or 30% Reduction in Pain at 4 Months | Baseline to 4 months | Percentage of patients who have either a 2 point or 30% reduction in (pain) NPRS at 4 Months. Absolute change in pain intensity as measured by the 11-point, numerical pain rating scale (NPRS) (0-10; where 0=no pain, to 10=worst possible pain). |
| Patient Global Impression at 4 Months | Baseline through 4 months. | Patient Global Impression at 4 Months. The question assesses change since the start of the study on a 7-point scale (Since the start of the study, how has your diabetic neuropathy in your legs changed?), and to score it as either very much worse, much worse, minimally worse, no change, minimally improved, much improved or very much improved. |
| Time to 30% or 2-point Reduction in NPRS, Whichever Comes First, Through 4 Months | Through 4 months | Absolute change in pain intensity as measured by the 11-point, numerical pain rating scale (NPRS) (0-10; where 0=no pain, to 10=worst possible pain). Number of participants achieving a 30% or 2-point reduction at or prior to weeks 1, 4, 8, 12 and 17 are displayed below. |
| Change in Neuropathy Related Quality of Life (NeuroQoL) Between Baseline and End of Treatment at 4 Months. | Baseline to 4 months | A validated set of health-related quality of life measures that are domain specific.Subjects will completed 6 domains: (1) Pain, (2) Lost/Reduced Feeling, (3) Diffuse Sensory Motor Symptoms, (4) Restrictions in Activities of Daily Living, (5) Disruptions in Social Relationships, and (6) Emotional Distress.The short forms were completed by the subject at the Enrollment Visit and end of study visit (Day 121). Each question in the domain was rated on a symptom scale from 1 (never) to 5 (all the time) and a bothersome scale from 1 (none) to 3 (very much). The total score for the domain was calculated by multiplying the symptom score by the bothersome score. The scale range is from 1 to 15 where the minimum (best/least symptomatic) score is 1 and the maximum (worst/most symptomatic) score is 15. The mean change from Baseline to month 4 is displayed below. |
| Change is Skin Perfusion Pressure (SPP) for Baseline to End of Treatment at 4 Months | Baseline to 4 months | SPP was measured at two locations on each foot (dorsal right and left and plantar right and left). Mean change displayed from Baseline to 4-months displayed below. SPP measures pressure in mmHg; an increase in pressure is favorable. * Normal SPP: 50 mmHg to 100 mmHg * Marginal Ischemia SPP: 30 mmHg to 50 mmHg * Critical Limb Ischemia / PAD SPP: \< 30 mmHg |
| Changes in Nerve Conduction Studies of Velocity Between Baseline and End of Treatment at 4 Months. | Baseline to 4 Months | Using the NC-stat DPNCheck, the sural nerve conduction velocity was recorded on the right and left legs. An increase in velocity would suggest DPN improvement. The mean change from Baseline to 4-months is displayed below. |
| Changes in Quantitative Sensory Testing (QST) Between Baseline and End of Treatment at 4 Months. | Baseline to 4 months | Contact thermal stimulation will be delivered using the Medoc Ltd. Q-Sense system to assess cool sensation threshold, warm sensation threshold and heat pain threshold modalities using the method of limits. Within the cool and warm sensation modalities, the trial is repeated 4 times on each foot and 3 times on each foot for heat pain threshold modality. The cool thermal testing will be conducted prior to the warm and heat pain thermal testing. Mean change from baseline to 4-months displayed below. |
| Changes in Nerve Conduction Studies of Amplitude Between Baseline and End of Treatment at 4 Months. | Baseline to 4 Months | Using the NC-stat DPNCheck, the sural nerve conduction amplitude was recorded on the right and left legs. An increase in amplitude would suggest DPN improvement. The mean change from Baseline to 4-months is displayed below. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Exploratory Endpoint: Changes in Intraepidermal Nerve Fiber Density (IENFD) at the Distal Thigh and Distal Leg - Part A | Baseline to Month 4 | Optional two 3 mm punch skin biopsies will be performed at baseline and end of treatment to assess IENFD. At the Enrollment Visit, one biopsy will be obtained at the distal leg, 10 cm above the lateral malleolus on the right leg and a second biopsy will be obtained at the distal thigh, 10 cm above the superior margin of the patella on the lateral right leg. At the end of Part A study visit Month 4 (Day 121), a second set of biopsies will be obtained lateral to the baseline biopsies and shipped overnight to the central lab. For Active Group and Sham Group displayed below, result are the change in nerve fiber density from Baseline to Month 4. |
| Exploratory Endpoint: Change in Pain Intensity During Part B | Baseline through 12 months | Absolute change in pain intensity as measured by the 11-point, numerical pain rating scale (NPRS) (0-10; where 0=no pain, to 10=worst possible pain). Results below display the change from Baseline to Month 12 for subjects that participated in the open-label extension (Part B), stratified by their original randomization in Part A. |
| Exploratory Endpoint: Changes in Nerve Conduction Studies of Velocity During Part B | Baseline to Month 12 | Using the NC-stat DPNCheck, the sural nerve conduction velocity was recorded on the right and left legs. An increase in velocity would suggest DPN improvement. Results below display the mean change in velocity and from Baseline to Month 12 for subjects that participated in the open-label extension (Part B), stratified by their original randomization in Part A. |
| Exploratory Endpoint: Change in Neuropathy Related Quality of Life (NeuroQoL) During Part B | Baseline to Month 12 | A validated set of health-related quality of life measures that are domain specific.Subjects will completed 6 domains: (1)Pain, (2)Lost/Reduced Feeling, (3)Diffuse Sensory Motor Symptoms, (4)Restrictions in Activities of Daily Living, (5)Disruptions in Social Relationships, and (6)Emotional Distress.The short forms were completed by the subject at the Enrollment Visit, end of study visit (Day 121) and at 12 months. Each question in the domain was rated on a symptom scale from 1 (never) to 5 (all the time) and a bothersome scale from 1 (none) to 3 (very much). The total score for the domain was calculated by multiplying the symptom score by the bothersome score. The scale range is from 1 to 15 where the minimum (best/least symptomatic) score is 1 and the maximum (worst/most symptomatic) score is 15. Results below display the change from Baseline to Month 12 for subjects that participated in the open-label extension (Part B), stratified by their original randomization in Part |
| Exploratory Endpoint: Changes in Nerve Conduction Studies of Amplitude During Part B | Baseline to Month 12 | Using the NC-stat DPNCheck, the sural nerve conduction amplitude was recorded on the right and left legs. An increase in amplitude would suggest DPN improvement. Results below display the mean change in amplitude from Baseline to Month 12 for subjects that participated in the open-label extension (Part B), stratified by their original randomization in Part A. |
| Exploratory Endpoint: Changes in the Work Productivity and Activity Impairment Questionnaire (WPAIQ) (Questions 5-6) | Baseline to 4 Months | The Work Productivity and Activity Impairment Questionnaire (WPAIQ) is a validated 6 question assessment tool that measures time missed from work, impairment of work and regular activities due to their health problem. Subjects are asked if they are working (Question 1), and if answer is yes, subjects are asked about the effect their diabetic neuropathy (DN) has on their ability to work and perform regular activities in the past 7 days. Mean change from Baseline to 4-months displayed below (Questions 5-6) for subjects that responded Yes to working in Question 1. Questions 5 and 6 use a 0-10 scale where 0 = no effect on work and/or daily activities and 10 =DN completely prevented me from working and/or doing daily activities. |
| Exploratory Endpoint: Changes in Intraepidermal Nerve Fiber Density (IENFD) at the Distal Thigh and Distal Leg - Part B | Baseline to Month 12 | Optional two 3 mm punch skin biopsies will be performed at baseline and end of treatment to assess IENFD. At the Enrollment Visit, one biopsy will be obtained at the distal leg, 10 cm above the lateral malleolus on the right leg and a second biopsy will be obtained at the distal thigh, 10 cm above the superior margin of the patella on the lateral right leg. At the end of Part A study visit Month 4 (Day 121), a second set of biopsies will be obtained lateral to the baseline biopsies and shipped overnight to the central lab. At the end of Part B study visit Month 12 (Day 361), a final set of biopsies will be obtained lateral to the Month 4 biopsies. Results displayed are the change in nerve fiber density from Baseline to Month 12 for subjects that participated in the open-label extension (Part B), stratified by their original randomization in Part A. |
| Exploratory Endpoint: Changes in the Work Productivity and Activity Impairment Questionnaire (WPAIQ) (Questions 2-4) | Baseline to 4 Months | The Work Productivity and Activity Impairment Questionnaire (WPAIQ) is a validated 6 question assessment tool that measures time missed from work, impairment of work and regular activities due to their health problem. Subjects are asked if they are working (Question 1), and if answer is yes, subjects are asked about the effect their diabetic neuropathy (DN) has on their ability to work and perform regular activities in the past 7 days. Mean change from Baseline to 4-months are displayed below (Questions 2-4) for subjects that responded Yes to working in Question 1. Questions 2-4 are answered in number of hours. |
Countries
United States
Participant flow
Pre-assignment details
Protocol Sample Size was anticipated at 170 subjects. The original enrollment target of 170 subjects was exceeded to grant study entry to qualified subjects that completed the 14-day run-in period.
Participants by arm
| Arm | Count |
|---|---|
| Active Group Treatment with active Provant Therapy System
Active Provant Therapy System: Treatment with active Provant Therapy System | 92 |
| Sham Group Treatment with in-active (sham) Provant Therapy System
Inactive (sham) Provant Therapy System: Treatment with inactive Provant Therapy System | 90 |
| Total | 182 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Part A: Randomized Treatment (17 Weeks) | Adverse Event | 2 | 5 | 0 |
| Part A: Randomized Treatment (17 Weeks) | Physician Decision | 2 | 0 | 0 |
| Part A: Randomized Treatment (17 Weeks) | Withdrawal by Subject | 7 | 2 | 0 |
| Part B: Open-label Extension (24 Weeks) | Adverse Event | 0 | 0 | 3 |
| Part B: Open-label Extension (24 Weeks) | Device interfered with home speakers | 0 | 0 | 1 |
| Part B: Open-label Extension (24 Weeks) | Lack of Efficacy | 0 | 0 | 7 |
| Part B: Open-label Extension (24 Weeks) | Lost to Follow-up | 0 | 0 | 4 |
| Part B: Open-label Extension (24 Weeks) | Out of window for visits | 0 | 0 | 2 |
| Part B: Open-label Extension (24 Weeks) | Withdrawal by Subject | 0 | 0 | 20 |
Baseline characteristics
| Characteristic | Active Group | Total | Sham Group |
|---|---|---|---|
| Age, Continuous | 62.27 years STANDARD_DEVIATION 10.21 | 62.22 years STANDARD_DEVIATION 9.76 | 62.17 years STANDARD_DEVIATION 9.33 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 12 Participants | 27 Participants | 15 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 80 Participants | 155 Participants | 75 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 4 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 15 Participants | 29 Participants | 14 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 74 Participants | 147 Participants | 73 Participants |
| Region of Enrollment United States | 92 participants | 182 participants | 90 participants |
| Sex: Female, Male Female | 50 Participants | 92 Participants | 42 Participants |
| Sex: Female, Male Male | 42 Participants | 90 Participants | 48 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 92 | 0 / 90 | 57 / 152 |
| other Total, other adverse events | 0 / 92 | 0 / 90 | 0 / 152 |
| serious Total, serious adverse events | 5 / 92 | 6 / 90 | 5 / 152 |
Outcome results
Primary
Change in Pain Intensity
Absolute change in pain intensity as measured by the 11-point, numerical pain rating scale (NPRS) (0-10; where 0=no pain, to 10=worst possible pain).
Time frame: Baseline through 4 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active Group | Change in Pain Intensity | -1.47 units on a scale | Standard Deviation 1.845 |
| Sham Group | Change in Pain Intensity | -1.25 units on a scale | Standard Deviation 2.018 |
Secondary
Change in Neuropathy Related Quality of Life (NeuroQoL) Between Baseline and End of Treatment at 4 Months.
A validated set of health-related quality of life measures that are domain specific.Subjects will completed 6 domains: (1) Pain, (2) Lost/Reduced Feeling, (3) Diffuse Sensory Motor Symptoms, (4) Restrictions in Activities of Daily Living, (5) Disruptions in Social Relationships, and (6) Emotional Distress.The short forms were completed by the subject at the Enrollment Visit and end of study visit (Day 121). Each question in the domain was rated on a symptom scale from 1 (never) to 5 (all the time) and a bothersome scale from 1 (none) to 3 (very much). The total score for the domain was calculated by multiplying the symptom score by the bothersome score. The scale range is from 1 to 15 where the minimum (best/least symptomatic) score is 1 and the maximum (worst/most symptomatic) score is 15. The mean change from Baseline to month 4 is displayed below.
Time frame: Baseline to 4 months
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Active Group | Change in Neuropathy Related Quality of Life (NeuroQoL) Between Baseline and End of Treatment at 4 Months. | (1) Pain | -1.66 units on a scale |
| Active Group | Change in Neuropathy Related Quality of Life (NeuroQoL) Between Baseline and End of Treatment at 4 Months. | (2) Lost/Reduced Feeling | -1.03 units on a scale |
| Active Group | Change in Neuropathy Related Quality of Life (NeuroQoL) Between Baseline and End of Treatment at 4 Months. | (3) Diffuse Sensory Motor Symptoms | -0.92 units on a scale |
| Active Group | Change in Neuropathy Related Quality of Life (NeuroQoL) Between Baseline and End of Treatment at 4 Months. | (4) Restrictions in Activities of Daily Living | -1.66 units on a scale |
| Active Group | Change in Neuropathy Related Quality of Life (NeuroQoL) Between Baseline and End of Treatment at 4 Months. | (5) Disruptions in Social Relationships | -1.31 units on a scale |
| Active Group | Change in Neuropathy Related Quality of Life (NeuroQoL) Between Baseline and End of Treatment at 4 Months. | (6) Emotional Distress | -1.12 units on a scale |
| Sham Group | Change in Neuropathy Related Quality of Life (NeuroQoL) Between Baseline and End of Treatment at 4 Months. | (5) Disruptions in Social Relationships | -1.99 units on a scale |
| Sham Group | Change in Neuropathy Related Quality of Life (NeuroQoL) Between Baseline and End of Treatment at 4 Months. | (1) Pain | -1.52 units on a scale |
| Sham Group | Change in Neuropathy Related Quality of Life (NeuroQoL) Between Baseline and End of Treatment at 4 Months. | (4) Restrictions in Activities of Daily Living | -2.38 units on a scale |
| Sham Group | Change in Neuropathy Related Quality of Life (NeuroQoL) Between Baseline and End of Treatment at 4 Months. | (2) Lost/Reduced Feeling | -1.42 units on a scale |
| Sham Group | Change in Neuropathy Related Quality of Life (NeuroQoL) Between Baseline and End of Treatment at 4 Months. | (6) Emotional Distress | -1.63 units on a scale |
| Sham Group | Change in Neuropathy Related Quality of Life (NeuroQoL) Between Baseline and End of Treatment at 4 Months. | (3) Diffuse Sensory Motor Symptoms | -0.79 units on a scale |
Secondary
Change is Skin Perfusion Pressure (SPP) for Baseline to End of Treatment at 4 Months
SPP was measured at two locations on each foot (dorsal right and left and plantar right and left). Mean change displayed from Baseline to 4-months displayed below. SPP measures pressure in mmHg; an increase in pressure is favorable. * Normal SPP: 50 mmHg to 100 mmHg * Marginal Ischemia SPP: 30 mmHg to 50 mmHg * Critical Limb Ischemia / PAD SPP: \< 30 mmHg
Time frame: Baseline to 4 months
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Active Group | Change is Skin Perfusion Pressure (SPP) for Baseline to End of Treatment at 4 Months | Dorsal - Left | -0.25 mmHg | Standard Deviation 34.22 |
| Active Group | Change is Skin Perfusion Pressure (SPP) for Baseline to End of Treatment at 4 Months | Dorsal - Right | -0.74 mmHg | Standard Deviation 35.18 |
| Active Group | Change is Skin Perfusion Pressure (SPP) for Baseline to End of Treatment at 4 Months | Plantar - Left | 6.37 mmHg | Standard Deviation 27.72 |
| Active Group | Change is Skin Perfusion Pressure (SPP) for Baseline to End of Treatment at 4 Months | Plantar - Right | 2.12 mmHg | Standard Deviation 21.05 |
| Sham Group | Change is Skin Perfusion Pressure (SPP) for Baseline to End of Treatment at 4 Months | Plantar - Right | -2.51 mmHg | Standard Deviation 23.66 |
| Sham Group | Change is Skin Perfusion Pressure (SPP) for Baseline to End of Treatment at 4 Months | Dorsal - Left | 3.27 mmHg | Standard Deviation 33.82 |
| Sham Group | Change is Skin Perfusion Pressure (SPP) for Baseline to End of Treatment at 4 Months | Plantar - Left | -1.84 mmHg | Standard Deviation 28.87 |
| Sham Group | Change is Skin Perfusion Pressure (SPP) for Baseline to End of Treatment at 4 Months | Dorsal - Right | 2.93 mmHg | Standard Deviation 25.83 |
Secondary
Changes in Nerve Conduction Studies of Amplitude Between Baseline and End of Treatment at 4 Months.
Using the NC-stat DPNCheck, the sural nerve conduction amplitude was recorded on the right and left legs. An increase in amplitude would suggest DPN improvement. The mean change from Baseline to 4-months is displayed below.
Time frame: Baseline to 4 Months
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Active Group | Changes in Nerve Conduction Studies of Amplitude Between Baseline and End of Treatment at 4 Months. | Amplitude (m/s) - Left | 1.27 uv (amplitude) | Standard Deviation 9.96 |
| Active Group | Changes in Nerve Conduction Studies of Amplitude Between Baseline and End of Treatment at 4 Months. | Amplitude (m/s) - Right | 1.95 uv (amplitude) | Standard Deviation 10.27 |
| Sham Group | Changes in Nerve Conduction Studies of Amplitude Between Baseline and End of Treatment at 4 Months. | Amplitude (m/s) - Right | 1.03 uv (amplitude) | Standard Deviation 9.91 |
| Sham Group | Changes in Nerve Conduction Studies of Amplitude Between Baseline and End of Treatment at 4 Months. | Amplitude (m/s) - Left | 1.36 uv (amplitude) | Standard Deviation 11.63 |
Secondary
Changes in Nerve Conduction Studies of Velocity Between Baseline and End of Treatment at 4 Months.
Using the NC-stat DPNCheck, the sural nerve conduction velocity was recorded on the right and left legs. An increase in velocity would suggest DPN improvement. The mean change from Baseline to 4-months is displayed below.
Time frame: Baseline to 4 Months
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Active Group | Changes in Nerve Conduction Studies of Velocity Between Baseline and End of Treatment at 4 Months. | Velocity (uv) - Left | -4.15 m/s (velocity) | Standard Deviation 20.45 |
| Active Group | Changes in Nerve Conduction Studies of Velocity Between Baseline and End of Treatment at 4 Months. | Velocity (uv) - Right | -1.11 m/s (velocity) | Standard Deviation 18.18 |
| Sham Group | Changes in Nerve Conduction Studies of Velocity Between Baseline and End of Treatment at 4 Months. | Velocity (uv) - Left | -5.12 m/s (velocity) | Standard Deviation 22.25 |
| Sham Group | Changes in Nerve Conduction Studies of Velocity Between Baseline and End of Treatment at 4 Months. | Velocity (uv) - Right | -5.06 m/s (velocity) | Standard Deviation 20.94 |
Secondary
Changes in Quantitative Sensory Testing (QST) Between Baseline and End of Treatment at 4 Months.
Contact thermal stimulation will be delivered using the Medoc Ltd. Q-Sense system to assess cool sensation threshold, warm sensation threshold and heat pain threshold modalities using the method of limits. Within the cool and warm sensation modalities, the trial is repeated 4 times on each foot and 3 times on each foot for heat pain threshold modality. The cool thermal testing will be conducted prior to the warm and heat pain thermal testing. Mean change from baseline to 4-months displayed below.
Time frame: Baseline to 4 months
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Active Group | Changes in Quantitative Sensory Testing (QST) Between Baseline and End of Treatment at 4 Months. | Cold - Right | 0.57 Temperature in degrees C | Standard Deviation 3.32 |
| Active Group | Changes in Quantitative Sensory Testing (QST) Between Baseline and End of Treatment at 4 Months. | Cold - Left | 0.08 Temperature in degrees C | Standard Deviation 3.25 |
| Active Group | Changes in Quantitative Sensory Testing (QST) Between Baseline and End of Treatment at 4 Months. | Warm - Right | -0.58 Temperature in degrees C | Standard Deviation 3.7 |
| Active Group | Changes in Quantitative Sensory Testing (QST) Between Baseline and End of Treatment at 4 Months. | Warm - Left | -0.53 Temperature in degrees C | Standard Deviation 4.25 |
| Active Group | Changes in Quantitative Sensory Testing (QST) Between Baseline and End of Treatment at 4 Months. | Pain - Right | -0.29 Temperature in degrees C | Standard Deviation 3.21 |
| Active Group | Changes in Quantitative Sensory Testing (QST) Between Baseline and End of Treatment at 4 Months. | Pain - Left | -0.62 Temperature in degrees C | Standard Deviation 3.23 |
| Sham Group | Changes in Quantitative Sensory Testing (QST) Between Baseline and End of Treatment at 4 Months. | Pain - Right | -0.75 Temperature in degrees C | Standard Deviation 3.1 |
| Sham Group | Changes in Quantitative Sensory Testing (QST) Between Baseline and End of Treatment at 4 Months. | Cold - Right | -0.21 Temperature in degrees C | Standard Deviation 3.07 |
| Sham Group | Changes in Quantitative Sensory Testing (QST) Between Baseline and End of Treatment at 4 Months. | Warm - Left | 0.01 Temperature in degrees C | Standard Deviation 4.41 |
| Sham Group | Changes in Quantitative Sensory Testing (QST) Between Baseline and End of Treatment at 4 Months. | Cold - Left | 0.02 Temperature in degrees C | Standard Deviation 2.85 |
| Sham Group | Changes in Quantitative Sensory Testing (QST) Between Baseline and End of Treatment at 4 Months. | Pain - Left | -0.23 Temperature in degrees C | Standard Deviation 2.97 |
| Sham Group | Changes in Quantitative Sensory Testing (QST) Between Baseline and End of Treatment at 4 Months. | Warm - Right | -0.54 Temperature in degrees C | Standard Deviation 4.07 |
Secondary
Patient Global Impression at 4 Months
Patient Global Impression at 4 Months. The question assesses change since the start of the study on a 7-point scale (Since the start of the study, how has your diabetic neuropathy in your legs changed?), and to score it as either very much worse, much worse, minimally worse, no change, minimally improved, much improved or very much improved.
Time frame: Baseline through 4 months.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Active Group | Patient Global Impression at 4 Months | No Change | 24 Participants |
| Active Group | Patient Global Impression at 4 Months | Much Improved | 16 Participants |
| Active Group | Patient Global Impression at 4 Months | Minimally Worse | 3 Participants |
| Active Group | Patient Global Impression at 4 Months | Very Much Improved | 3 Participants |
| Active Group | Patient Global Impression at 4 Months | Minimally Improved | 37 Participants |
| Active Group | Patient Global Impression at 4 Months | Not reported | 8 Participants |
| Active Group | Patient Global Impression at 4 Months | Much Worse | 1 Participants |
| Sham Group | Patient Global Impression at 4 Months | Not reported | 3 Participants |
| Sham Group | Patient Global Impression at 4 Months | Much Worse | 2 Participants |
| Sham Group | Patient Global Impression at 4 Months | Minimally Worse | 11 Participants |
| Sham Group | Patient Global Impression at 4 Months | No Change | 28 Participants |
| Sham Group | Patient Global Impression at 4 Months | Minimally Improved | 23 Participants |
| Sham Group | Patient Global Impression at 4 Months | Much Improved | 20 Participants |
| Sham Group | Patient Global Impression at 4 Months | Very Much Improved | 3 Participants |
Secondary
Patients With 2 Point or 30% Reduction in Pain at 4 Months
Percentage of patients who have either a 2 point or 30% reduction in (pain) NPRS at 4 Months. Absolute change in pain intensity as measured by the 11-point, numerical pain rating scale (NPRS) (0-10; where 0=no pain, to 10=worst possible pain).
Time frame: Baseline to 4 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Active Group | Patients With 2 Point or 30% Reduction in Pain at 4 Months | 28 Participants |
| Sham Group | Patients With 2 Point or 30% Reduction in Pain at 4 Months | 26 Participants |
Secondary
Time to 30% or 2-point Reduction in NPRS, Whichever Comes First, Through 4 Months
Absolute change in pain intensity as measured by the 11-point, numerical pain rating scale (NPRS) (0-10; where 0=no pain, to 10=worst possible pain). Number of participants achieving a 30% or 2-point reduction at or prior to weeks 1, 4, 8, 12 and 17 are displayed below.
Time frame: Through 4 months
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Active Group | Time to 30% or 2-point Reduction in NPRS, Whichever Comes First, Through 4 Months | Week 1 | 4 Participants |
| Active Group | Time to 30% or 2-point Reduction in NPRS, Whichever Comes First, Through 4 Months | Week 12 | 43 Participants |
| Active Group | Time to 30% or 2-point Reduction in NPRS, Whichever Comes First, Through 4 Months | Week 4 | 18 Participants |
| Active Group | Time to 30% or 2-point Reduction in NPRS, Whichever Comes First, Through 4 Months | Week 17 | 45 Participants |
| Active Group | Time to 30% or 2-point Reduction in NPRS, Whichever Comes First, Through 4 Months | Week 8 | 32 Participants |
| Sham Group | Time to 30% or 2-point Reduction in NPRS, Whichever Comes First, Through 4 Months | Week 17 | 40 Participants |
| Sham Group | Time to 30% or 2-point Reduction in NPRS, Whichever Comes First, Through 4 Months | Week 1 | 3 Participants |
| Sham Group | Time to 30% or 2-point Reduction in NPRS, Whichever Comes First, Through 4 Months | Week 8 | 27 Participants |
| Sham Group | Time to 30% or 2-point Reduction in NPRS, Whichever Comes First, Through 4 Months | Week 12 | 34 Participants |
| Sham Group | Time to 30% or 2-point Reduction in NPRS, Whichever Comes First, Through 4 Months | Week 4 | 18 Participants |
Other Pre-specified
Exploratory Endpoint: Change in Neuropathy Related Quality of Life (NeuroQoL) During Part B
A validated set of health-related quality of life measures that are domain specific.Subjects will completed 6 domains: (1)Pain, (2)Lost/Reduced Feeling, (3)Diffuse Sensory Motor Symptoms, (4)Restrictions in Activities of Daily Living, (5)Disruptions in Social Relationships, and (6)Emotional Distress.The short forms were completed by the subject at the Enrollment Visit, end of study visit (Day 121) and at 12 months. Each question in the domain was rated on a symptom scale from 1 (never) to 5 (all the time) and a bothersome scale from 1 (none) to 3 (very much). The total score for the domain was calculated by multiplying the symptom score by the bothersome score. The scale range is from 1 to 15 where the minimum (best/least symptomatic) score is 1 and the maximum (worst/most symptomatic) score is 15. Results below display the change from Baseline to Month 12 for subjects that participated in the open-label extension (Part B), stratified by their original randomization in Part
Time frame: Baseline to Month 12
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Active Group | Exploratory Endpoint: Change in Neuropathy Related Quality of Life (NeuroQoL) During Part B | (1) Pain | -3.14 units on a scale | Standard Deviation 2.33 |
| Active Group | Exploratory Endpoint: Change in Neuropathy Related Quality of Life (NeuroQoL) During Part B | (2) Lost/Reduced Feeling | -2.42 units on a scale | Standard Deviation 2.99 |
| Active Group | Exploratory Endpoint: Change in Neuropathy Related Quality of Life (NeuroQoL) During Part B | (3) Diffuse Sensory Motor | -1.58 units on a scale | Standard Deviation 2.78 |
| Active Group | Exploratory Endpoint: Change in Neuropathy Related Quality of Life (NeuroQoL) During Part B | (4) Restrictions in Activities | -2.67 units on a scale | Standard Deviation 3.61 |
| Active Group | Exploratory Endpoint: Change in Neuropathy Related Quality of Life (NeuroQoL) During Part B | (5) Distruptions in Social Relationships | -2.25 units on a scale | Standard Deviation 3.73 |
| Active Group | Exploratory Endpoint: Change in Neuropathy Related Quality of Life (NeuroQoL) During Part B | (6) Emotional Distress | -1.60 units on a scale | Standard Deviation 3.81 |
| Sham Group | Exploratory Endpoint: Change in Neuropathy Related Quality of Life (NeuroQoL) During Part B | (5) Distruptions in Social Relationships | -1.73 units on a scale | Standard Deviation 3.96 |
| Sham Group | Exploratory Endpoint: Change in Neuropathy Related Quality of Life (NeuroQoL) During Part B | (1) Pain | -2.88 units on a scale | Standard Deviation 3.19 |
| Sham Group | Exploratory Endpoint: Change in Neuropathy Related Quality of Life (NeuroQoL) During Part B | (4) Restrictions in Activities | -2.14 units on a scale | Standard Deviation 4.85 |
| Sham Group | Exploratory Endpoint: Change in Neuropathy Related Quality of Life (NeuroQoL) During Part B | (2) Lost/Reduced Feeling | -1.96 units on a scale | Standard Deviation 4.07 |
| Sham Group | Exploratory Endpoint: Change in Neuropathy Related Quality of Life (NeuroQoL) During Part B | (6) Emotional Distress | -1.79 units on a scale | Standard Deviation 3.58 |
| Sham Group | Exploratory Endpoint: Change in Neuropathy Related Quality of Life (NeuroQoL) During Part B | (3) Diffuse Sensory Motor | -1.04 units on a scale | Standard Deviation 3.41 |
Other Pre-specified
Exploratory Endpoint: Change in Pain Intensity During Part B
Absolute change in pain intensity as measured by the 11-point, numerical pain rating scale (NPRS) (0-10; where 0=no pain, to 10=worst possible pain). Results below display the change from Baseline to Month 12 for subjects that participated in the open-label extension (Part B), stratified by their original randomization in Part A.
Time frame: Baseline through 12 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active Group | Exploratory Endpoint: Change in Pain Intensity During Part B | -2.96 units on a scale | Standard Deviation 2.38 |
| Sham Group | Exploratory Endpoint: Change in Pain Intensity During Part B | 2.49 units on a scale | Standard Deviation 2.38 |
Other Pre-specified
Exploratory Endpoint: Changes in Intraepidermal Nerve Fiber Density (IENFD) at the Distal Thigh and Distal Leg - Part A
Optional two 3 mm punch skin biopsies will be performed at baseline and end of treatment to assess IENFD. At the Enrollment Visit, one biopsy will be obtained at the distal leg, 10 cm above the lateral malleolus on the right leg and a second biopsy will be obtained at the distal thigh, 10 cm above the superior margin of the patella on the lateral right leg. At the end of Part A study visit Month 4 (Day 121), a second set of biopsies will be obtained lateral to the baseline biopsies and shipped overnight to the central lab. For Active Group and Sham Group displayed below, result are the change in nerve fiber density from Baseline to Month 4.
Time frame: Baseline to Month 4
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Active Group | Exploratory Endpoint: Changes in Intraepidermal Nerve Fiber Density (IENFD) at the Distal Thigh and Distal Leg - Part A | Right Distal Leg | -0.12 nerve fiber density in fibers/mm | Standard Deviation 1.6 |
| Active Group | Exploratory Endpoint: Changes in Intraepidermal Nerve Fiber Density (IENFD) at the Distal Thigh and Distal Leg - Part A | Right Distal Thigh | 0.64 nerve fiber density in fibers/mm | Standard Deviation 2.93 |
| Sham Group | Exploratory Endpoint: Changes in Intraepidermal Nerve Fiber Density (IENFD) at the Distal Thigh and Distal Leg - Part A | Right Distal Leg | 0.73 nerve fiber density in fibers/mm | Standard Deviation 2.33 |
| Sham Group | Exploratory Endpoint: Changes in Intraepidermal Nerve Fiber Density (IENFD) at the Distal Thigh and Distal Leg - Part A | Right Distal Thigh | 1.68 nerve fiber density in fibers/mm | Standard Deviation 2.63 |
Other Pre-specified
Exploratory Endpoint: Changes in Intraepidermal Nerve Fiber Density (IENFD) at the Distal Thigh and Distal Leg - Part B
Optional two 3 mm punch skin biopsies will be performed at baseline and end of treatment to assess IENFD. At the Enrollment Visit, one biopsy will be obtained at the distal leg, 10 cm above the lateral malleolus on the right leg and a second biopsy will be obtained at the distal thigh, 10 cm above the superior margin of the patella on the lateral right leg. At the end of Part A study visit Month 4 (Day 121), a second set of biopsies will be obtained lateral to the baseline biopsies and shipped overnight to the central lab. At the end of Part B study visit Month 12 (Day 361), a final set of biopsies will be obtained lateral to the Month 4 biopsies. Results displayed are the change in nerve fiber density from Baseline to Month 12 for subjects that participated in the open-label extension (Part B), stratified by their original randomization in Part A.
Time frame: Baseline to Month 12
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Active Group | Exploratory Endpoint: Changes in Intraepidermal Nerve Fiber Density (IENFD) at the Distal Thigh and Distal Leg - Part B | Right Distal Leg | .22 nerve fiber density in fibers/mm | Standard Deviation 2.17 |
| Active Group | Exploratory Endpoint: Changes in Intraepidermal Nerve Fiber Density (IENFD) at the Distal Thigh and Distal Leg - Part B | Right Distal Thigh | 1.09 nerve fiber density in fibers/mm | Standard Deviation 2.94 |
Other Pre-specified
Exploratory Endpoint: Changes in Nerve Conduction Studies of Amplitude During Part B
Using the NC-stat DPNCheck, the sural nerve conduction amplitude was recorded on the right and left legs. An increase in amplitude would suggest DPN improvement. Results below display the mean change in amplitude from Baseline to Month 12 for subjects that participated in the open-label extension (Part B), stratified by their original randomization in Part A.
Time frame: Baseline to Month 12
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Active Group | Exploratory Endpoint: Changes in Nerve Conduction Studies of Amplitude During Part B | Amplitude (uv) - Right | 6.0 uv (amplitude) and m/s (velocity) | Standard Deviation 15.3 |
| Active Group | Exploratory Endpoint: Changes in Nerve Conduction Studies of Amplitude During Part B | Amplitude (uv) - Left | 5.28 uv (amplitude) and m/s (velocity) | Standard Deviation 14.4 |
| Sham Group | Exploratory Endpoint: Changes in Nerve Conduction Studies of Amplitude During Part B | Amplitude (uv) - Left | 4.42 uv (amplitude) and m/s (velocity) | Standard Deviation 14.6 |
| Sham Group | Exploratory Endpoint: Changes in Nerve Conduction Studies of Amplitude During Part B | Amplitude (uv) - Right | 4.28 uv (amplitude) and m/s (velocity) | Standard Deviation 14.2 |
Other Pre-specified
Exploratory Endpoint: Changes in Nerve Conduction Studies of Velocity During Part B
Using the NC-stat DPNCheck, the sural nerve conduction velocity was recorded on the right and left legs. An increase in velocity would suggest DPN improvement. Results below display the mean change in velocity and from Baseline to Month 12 for subjects that participated in the open-label extension (Part B), stratified by their original randomization in Part A.
Time frame: Baseline to Month 12
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Active Group | Exploratory Endpoint: Changes in Nerve Conduction Studies of Velocity During Part B | Velocity (m/s) - Left | -11.9 m/s (velocity) | Standard Deviation 26 |
| Active Group | Exploratory Endpoint: Changes in Nerve Conduction Studies of Velocity During Part B | Velocity (m/s) - Right | -9.48 m/s (velocity) | Standard Deviation 19.5 |
| Sham Group | Exploratory Endpoint: Changes in Nerve Conduction Studies of Velocity During Part B | Velocity (m/s) - Left | -8.64 m/s (velocity) | Standard Deviation 24.7 |
| Sham Group | Exploratory Endpoint: Changes in Nerve Conduction Studies of Velocity During Part B | Velocity (m/s) - Right | -6.31 m/s (velocity) | Standard Deviation 22.9 |
Other Pre-specified
Exploratory Endpoint: Changes in the Work Productivity and Activity Impairment Questionnaire (WPAIQ) (Questions 2-4)
The Work Productivity and Activity Impairment Questionnaire (WPAIQ) is a validated 6 question assessment tool that measures time missed from work, impairment of work and regular activities due to their health problem. Subjects are asked if they are working (Question 1), and if answer is yes, subjects are asked about the effect their diabetic neuropathy (DN) has on their ability to work and perform regular activities in the past 7 days. Mean change from Baseline to 4-months are displayed below (Questions 2-4) for subjects that responded Yes to working in Question 1. Questions 2-4 are answered in number of hours.
Time frame: Baseline to 4 Months
Population: Includes only subjects that indicated they were working at the Enrollment Visit (Question 1).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Active Group | Exploratory Endpoint: Changes in the Work Productivity and Activity Impairment Questionnaire (WPAIQ) (Questions 2-4) | Work hours missed in past 7 days due to DN | 0.12 Hours | Standard Deviation 2.96 |
| Active Group | Exploratory Endpoint: Changes in the Work Productivity and Activity Impairment Questionnaire (WPAIQ) (Questions 2-4) | Work hours missed in past 7 days not due to DN | 0.60 Hours | Standard Deviation 9.17 |
| Active Group | Exploratory Endpoint: Changes in the Work Productivity and Activity Impairment Questionnaire (WPAIQ) (Questions 2-4) | Hours worked in past 7 days | -0.48 Hours | Standard Deviation 10.62 |
| Sham Group | Exploratory Endpoint: Changes in the Work Productivity and Activity Impairment Questionnaire (WPAIQ) (Questions 2-4) | Work hours missed in past 7 days due to DN | 0.33 Hours | Standard Deviation 1.89 |
| Sham Group | Exploratory Endpoint: Changes in the Work Productivity and Activity Impairment Questionnaire (WPAIQ) (Questions 2-4) | Work hours missed in past 7 days not due to DN | 2.61 Hours | Standard Deviation 9.38 |
| Sham Group | Exploratory Endpoint: Changes in the Work Productivity and Activity Impairment Questionnaire (WPAIQ) (Questions 2-4) | Hours worked in past 7 days | -2.11 Hours | Standard Deviation 20.8 |
Other Pre-specified
Exploratory Endpoint: Changes in the Work Productivity and Activity Impairment Questionnaire (WPAIQ) (Questions 5-6)
The Work Productivity and Activity Impairment Questionnaire (WPAIQ) is a validated 6 question assessment tool that measures time missed from work, impairment of work and regular activities due to their health problem. Subjects are asked if they are working (Question 1), and if answer is yes, subjects are asked about the effect their diabetic neuropathy (DN) has on their ability to work and perform regular activities in the past 7 days. Mean change from Baseline to 4-months displayed below (Questions 5-6) for subjects that responded Yes to working in Question 1. Questions 5 and 6 use a 0-10 scale where 0 = no effect on work and/or daily activities and 10 =DN completely prevented me from working and/or doing daily activities.
Time frame: Baseline to 4 Months
Population: Includes only subjects that indicated they were working at the Enrollment Visit (Question 1).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Active Group | Exploratory Endpoint: Changes in the Work Productivity and Activity Impairment Questionnaire (WPAIQ) (Questions 5-6) | Effect of DN on work in past 7 days | -0.40 units on a scale | Standard Deviation 1.89 |
| Active Group | Exploratory Endpoint: Changes in the Work Productivity and Activity Impairment Questionnaire (WPAIQ) (Questions 5-6) | Effect on daily activities in past 7 days | -0.67 units on a scale | Standard Deviation 2.19 |
| Sham Group | Exploratory Endpoint: Changes in the Work Productivity and Activity Impairment Questionnaire (WPAIQ) (Questions 5-6) | Effect of DN on work in past 7 days | -0.61 units on a scale | Standard Deviation 3.01 |
| Sham Group | Exploratory Endpoint: Changes in the Work Productivity and Activity Impairment Questionnaire (WPAIQ) (Questions 5-6) | Effect on daily activities in past 7 days | -0.59 units on a scale | Standard Deviation 2.7 |