Trial Outcomes & Findings for Dual Field PEMF Therapy in Lower Extremity Painful Diabetic Distal Symmetric Peripheral Neuropathy (NCT NCT03455543)

Results Overview

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).

Recruitment status

COMPLETED

Study phase

NA

Target enrollment

182 participants

Primary outcome timeframe

Baseline through 4 months

Results posted on

2020-07-15

Participant Flow

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.

Participant milestones

Participant milestones
Measure	Active Group Treatment with active Provant Therapy System Active Provant Therapy System: Treatment with active Provant Therapy System	Sham Group Treatment with in-active (sham) Provant Therapy System Inactive (sham) Provant Therapy System: Treatment with inactive Provant Therapy System	Open-label Extension Group (Part B) Subjects receiving open-label active PEMF therapy in Part B after 17 weeks of randomized treatment in Part A.
Part A: Randomized Treatment (17 Weeks) STARTED	92	90	0
Part A: Randomized Treatment (17 Weeks) COMPLETED	81	83	0
Part A: Randomized Treatment (17 Weeks) NOT COMPLETED	11	7	0
Part B: Open-label Extension (24 Weeks) STARTED	0	0	152
Part B: Open-label Extension (24 Weeks) COMPLETED	0	0	115
Part B: Open-label Extension (24 Weeks) NOT COMPLETED	0	0	37

Reasons for withdrawal

Reasons for withdrawal
Measure	Active Group Treatment with active Provant Therapy System Active Provant Therapy System: Treatment with active Provant Therapy System	Sham Group Treatment with in-active (sham) Provant Therapy System Inactive (sham) Provant Therapy System: Treatment with inactive Provant Therapy System	Open-label Extension Group (Part B) Subjects receiving open-label active PEMF therapy in Part B after 17 weeks of randomized treatment in Part A.
Part A: Randomized Treatment (17 Weeks) Adverse Event	2	5	0
Part A: Randomized Treatment (17 Weeks) Withdrawal by Subject	7	2	0
Part A: Randomized Treatment (17 Weeks) Physician Decision	2	0	0
Part B: Open-label Extension (24 Weeks) Adverse Event	0	0	3
Part B: Open-label Extension (24 Weeks) Withdrawal by Subject	0	0	20
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) Device interfered with home speakers	0	0	1

Baseline Characteristics

Dual Field PEMF Therapy in Lower Extremity Painful Diabetic Distal Symmetric Peripheral Neuropathy

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Active Group n=92 Participants Treatment with active Provant Therapy System Active Provant Therapy System: Treatment with active Provant Therapy System	Sham Group n=90 Participants Treatment with in-active (sham) Provant Therapy System Inactive (sham) Provant Therapy System: Treatment with inactive Provant Therapy System	Total n=182 Participants Total of all reporting groups
Age, Continuous	62.27 years STANDARD_DEVIATION 10.21 • n=93 Participants	62.17 years STANDARD_DEVIATION 9.33 • n=4 Participants	62.22 years STANDARD_DEVIATION 9.76 • n=27 Participants
Sex: Female, Male Female	50 Participants n=93 Participants	42 Participants n=4 Participants	92 Participants n=27 Participants
Sex: Female, Male Male	42 Participants n=93 Participants	48 Participants n=4 Participants	90 Participants n=27 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	12 Participants n=93 Participants	15 Participants n=4 Participants	27 Participants n=27 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	80 Participants n=93 Participants	75 Participants n=4 Participants	155 Participants n=27 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=93 Participants	1 Participants n=4 Participants	1 Participants n=27 Participants
Race (NIH/OMB) Asian	3 Participants n=93 Participants	1 Participants n=4 Participants	4 Participants n=27 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Black or African American	15 Participants n=93 Participants	14 Participants n=4 Participants	29 Participants n=27 Participants
Race (NIH/OMB) White	74 Participants n=93 Participants	73 Participants n=4 Participants	147 Participants n=27 Participants
Race (NIH/OMB) More than one race	0 Participants n=93 Participants	1 Participants n=4 Participants	1 Participants n=27 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Region of Enrollment United States	92 participants n=93 Participants	90 participants n=4 Participants	182 participants n=27 Participants

PRIMARY outcome

Timeframe: 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).

Outcome measures

Outcome measures
Measure	Active Group n=92 Participants Treatment with active Provant Therapy System Active Provant Therapy System: Treatment with active Provant Therapy System	Sham Group n=90 Participants Treatment with in-active (sham) Provant Therapy System Inactive (sham) Provant Therapy System: Treatment with inactive Provant Therapy System
Change in Pain Intensity	-1.47 units on a scale Standard Deviation 1.845	-1.25 units on a scale Standard Deviation 2.018

SECONDARY outcome

Timeframe: 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).

Outcome measures

Outcome measures
Measure	Active Group n=92 Participants Treatment with active Provant Therapy System Active Provant Therapy System: Treatment with active Provant Therapy System	Sham Group n=90 Participants Treatment with in-active (sham) Provant Therapy System Inactive (sham) Provant Therapy System: Treatment with inactive Provant Therapy System
Patients With 2 Point or 30% Reduction in Pain at 4 Months	28 Participants	26 Participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Active Group n=92 Participants Treatment with active Provant Therapy System Active Provant Therapy System: Treatment with active Provant Therapy System	Sham Group n=90 Participants Treatment with in-active (sham) Provant Therapy System Inactive (sham) Provant Therapy System: Treatment with inactive Provant Therapy System
Patient Global Impression at 4 Months Much Worse	1 Participants	2 Participants
Patient Global Impression at 4 Months Minimally Worse	3 Participants	11 Participants
Patient Global Impression at 4 Months No Change	24 Participants	28 Participants
Patient Global Impression at 4 Months Minimally Improved	37 Participants	23 Participants
Patient Global Impression at 4 Months Much Improved	16 Participants	20 Participants
Patient Global Impression at 4 Months Very Much Improved	3 Participants	3 Participants
Patient Global Impression at 4 Months Not reported	8 Participants	3 Participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Active Group n=92 Participants Treatment with active Provant Therapy System Active Provant Therapy System: Treatment with active Provant Therapy System	Sham Group n=90 Participants Treatment with in-active (sham) Provant Therapy System Inactive (sham) Provant Therapy System: Treatment with inactive Provant Therapy System
Time to 30% or 2-point Reduction in NPRS, Whichever Comes First, Through 4 Months Week 1	4 Participants	3 Participants
Time to 30% or 2-point Reduction in NPRS, Whichever Comes First, Through 4 Months Week 4	18 Participants	18 Participants
Time to 30% or 2-point Reduction in NPRS, Whichever Comes First, Through 4 Months Week 8	32 Participants	27 Participants
Time to 30% or 2-point Reduction in NPRS, Whichever Comes First, Through 4 Months Week 12	43 Participants	34 Participants
Time to 30% or 2-point Reduction in NPRS, Whichever Comes First, Through 4 Months Week 17	45 Participants	40 Participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Active Group n=92 Participants Treatment with active Provant Therapy System Active Provant Therapy System: Treatment with active Provant Therapy System	Sham Group n=90 Participants Treatment with in-active (sham) Provant Therapy System Inactive (sham) Provant Therapy System: Treatment with inactive Provant Therapy System
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 Interval -2.22 to -1.11	-1.52 units on a scale Interval -2.13 to -0.91
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 Interval -1.67 to -0.4	-1.42 units on a scale Interval -2.16 to -0.68
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 Interval -1.53 to -0.3	-0.79 units on a scale Interval -1.48 to -0.09
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 Interval -2.38 to -0.93	-2.38 units on a scale Interval -3.16 to -1.6
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 Interval -1.99 to -0.62	-1.99 units on a scale Interval -2.7 to -1.29
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 Interval -1.68 to -0.55	-1.63 units on a scale Interval -2.33 to -0.93

SECONDARY outcome

Timeframe: 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

Outcome measures

Outcome measures
Measure	Active Group n=92 Participants Treatment with active Provant Therapy System Active Provant Therapy System: Treatment with active Provant Therapy System	Sham Group n=90 Participants Treatment with in-active (sham) Provant Therapy System Inactive (sham) Provant Therapy System: Treatment with inactive Provant Therapy System
Change is Skin Perfusion Pressure (SPP) for Baseline to End of Treatment at 4 Months Dorsal - Left	-0.25 mmHg Standard Deviation 34.22	3.27 mmHg Standard Deviation 33.82
Change is Skin Perfusion Pressure (SPP) for Baseline to End of Treatment at 4 Months Dorsal - Right	-0.74 mmHg Standard Deviation 35.18	2.93 mmHg Standard Deviation 25.83
Change is Skin Perfusion Pressure (SPP) for Baseline to End of Treatment at 4 Months Plantar - Left	6.37 mmHg Standard Deviation 27.72	-1.84 mmHg Standard Deviation 28.87
Change is Skin Perfusion Pressure (SPP) for Baseline to End of Treatment at 4 Months Plantar - Right	2.12 mmHg Standard Deviation 21.05	-2.51 mmHg Standard Deviation 23.66

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Active Group n=92 Participants Treatment with active Provant Therapy System Active Provant Therapy System: Treatment with active Provant Therapy System	Sham Group n=90 Participants Treatment with in-active (sham) Provant Therapy System Inactive (sham) Provant Therapy System: Treatment with inactive Provant Therapy System
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	-5.12 m/s (velocity) Standard Deviation 22.25
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	-5.06 m/s (velocity) Standard Deviation 20.94

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Active Group n=92 Participants Treatment with active Provant Therapy System Active Provant Therapy System: Treatment with active Provant Therapy System	Sham Group n=90 Participants Treatment with in-active (sham) Provant Therapy System Inactive (sham) Provant Therapy System: Treatment with inactive Provant Therapy System
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	-0.21 Temperature in degrees C Standard Deviation 3.07
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	0.02 Temperature in degrees C Standard Deviation 2.85
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 3.70	-0.54 Temperature in degrees C Standard Deviation 4.07
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	0.01 Temperature in degrees C Standard Deviation 4.41
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	-0.75 Temperature in degrees C Standard Deviation 3.10
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	-0.23 Temperature in degrees C Standard Deviation 2.97

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Active Group n=92 Participants Treatment with active Provant Therapy System Active Provant Therapy System: Treatment with active Provant Therapy System	Sham Group n=90 Participants Treatment with in-active (sham) Provant Therapy System Inactive (sham) Provant Therapy System: Treatment with inactive Provant Therapy System
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	1.36 uv (amplitude) Standard Deviation 11.63
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	1.03 uv (amplitude) Standard Deviation 9.91

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline to 4 Months

Population: Includes only subjects that indicated they were working at the Enrollment Visit (Question 1).

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.

Outcome measures

Outcome measures
Measure	Active Group n=29 Participants Treatment with active Provant Therapy System Active Provant Therapy System: Treatment with active Provant Therapy System	Sham Group n=18 Participants Treatment with in-active (sham) Provant Therapy System Inactive (sham) Provant Therapy System: Treatment with inactive Provant Therapy System
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	0.33 Hours Standard Deviation 1.89
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	2.61 Hours Standard Deviation 9.38
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	-2.11 Hours Standard Deviation 20.80

OTHER_PRE_SPECIFIED outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Active Group n=32 Participants Treatment with active Provant Therapy System Active Provant Therapy System: Treatment with active Provant Therapy System	Sham Group n=38 Participants Treatment with in-active (sham) Provant Therapy System Inactive (sham) Provant Therapy System: Treatment with inactive Provant Therapy System
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 1.60	0.73 nerve fiber density in fibers/mm Standard Deviation 2.33
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	1.68 nerve fiber density in fibers/mm Standard Deviation 2.63

OTHER_PRE_SPECIFIED outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Active Group n=72 Participants Treatment with active Provant Therapy System Active Provant Therapy System: Treatment with active Provant Therapy System	Sham Group n=80 Participants Treatment with in-active (sham) Provant Therapy System Inactive (sham) Provant Therapy System: Treatment with inactive Provant Therapy System
Exploratory Endpoint: Change in Pain Intensity During Part B	-2.96 units on a scale Standard Deviation 2.38	2.49 units on a scale Standard Deviation 2.38

OTHER_PRE_SPECIFIED outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Active Group n=72 Participants Treatment with active Provant Therapy System Active Provant Therapy System: Treatment with active Provant Therapy System	Sham Group n=80 Participants Treatment with in-active (sham) Provant Therapy System Inactive (sham) Provant Therapy System: Treatment with inactive Provant Therapy System
Exploratory Endpoint: Changes in Nerve Conduction Studies of Velocity During Part B Velocity (m/s) - Left	-11.9 m/s (velocity) Standard Deviation 26.0	-8.64 m/s (velocity) Standard Deviation 24.7
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	-6.31 m/s (velocity) Standard Deviation 22.9

OTHER_PRE_SPECIFIED outcome

Timeframe: 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

Outcome measures

Outcome measures
Measure	Active Group n=72 Participants Treatment with active Provant Therapy System Active Provant Therapy System: Treatment with active Provant Therapy System	Sham Group n=80 Participants Treatment with in-active (sham) Provant Therapy System Inactive (sham) Provant Therapy System: Treatment with inactive Provant Therapy System
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	-2.88 units on a scale Standard Deviation 3.19
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	-1.96 units on a scale Standard Deviation 4.07
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	-1.04 units on a scale Standard Deviation 3.41
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	-2.14 units on a scale Standard Deviation 4.85
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	-1.73 units on a scale Standard Deviation 3.96
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	-1.79 units on a scale Standard Deviation 3.58

OTHER_PRE_SPECIFIED outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Active Group n=72 Participants Treatment with active Provant Therapy System Active Provant Therapy System: Treatment with active Provant Therapy System	Sham Group n=80 Participants Treatment with in-active (sham) Provant Therapy System Inactive (sham) Provant Therapy System: Treatment with inactive Provant Therapy System
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	4.42 uv (amplitude) and m/s (velocity) Standard Deviation 14.6
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	4.28 uv (amplitude) and m/s (velocity) Standard Deviation 14.2

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline to 4 Months

Population: Includes only subjects that indicated they were working at the Enrollment Visit (Question 1).

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.

Outcome measures

Outcome measures
Measure	Active Group n=29 Participants Treatment with active Provant Therapy System Active Provant Therapy System: Treatment with active Provant Therapy System	Sham Group n=18 Participants Treatment with in-active (sham) Provant Therapy System Inactive (sham) Provant Therapy System: Treatment with inactive Provant Therapy System
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	-0.61 units on a scale Standard Deviation 3.01
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	-0.59 units on a scale Standard Deviation 2.70

OTHER_PRE_SPECIFIED outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Active Group n=57 Participants Treatment with active Provant Therapy System Active Provant Therapy System: Treatment with active Provant Therapy System	Sham Group Treatment with in-active (sham) Provant Therapy System Inactive (sham) Provant Therapy System: Treatment with inactive Provant Therapy System
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	—
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	—

Adverse Events

Active Group (Part A)

Serious events: 5 serious events

Other events: 0 other events

Deaths: 0 deaths

Sham Group (Part A)

Serious events: 6 serious events

Other events: 0 other events

Deaths: 0 deaths

Open-label Extension Group (Part B)

Serious events: 5 serious events

Other events: 0 other events

Deaths: 57 deaths

Serious adverse events

Other adverse events

Adverse event data not reported

Additional Information

Heather Vander Ploeg

Regenesis Biomedical

Phone: 602-428-7041

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Publication Rights. Independent analysis and/or publication of data generated or arising from the performance of this Agreement is not permitted without the prior written consent of Regenesis. Such consent may be contingent on Regenesis' review and approval of any proposed analysis and manuscript. Institution will retain the right to review and analyze the database created from this study for its own scientific purposes so long as such scientific purposes are non-commercial in nature.
Publication restrictions are in place

Restriction type: OTHER

Measure	Active Group (Part A) n=92 participants at risk Treatment with active Provant Therapy System Active Provant Therapy System: Treatment with active Provant Therapy System	Sham Group (Part A) n=90 participants at risk Treatment with in-active (sham) Provant Therapy System Inactive (sham) Provant Therapy System: Treatment with inactive Provant Therapy System	Open-label Extension Group (Part B) n=152 participants at risk Treatment with open-label active Provant Therapy System during Part B (months 4-12)
Gastrointestinal disorders Pancreatitis	1.1% 1/92 • Number of events 1 • Part A: 4 months (Baseline to Month 4); Part B: 8 months (Month 4 to Month 12)	0.00% 0/90 • Part A: 4 months (Baseline to Month 4); Part B: 8 months (Month 4 to Month 12)	0.00% 0/152 • Part A: 4 months (Baseline to Month 4); Part B: 8 months (Month 4 to Month 12)
Metabolism and nutrition disorders Dehydration	1.1% 1/92 • Number of events 1 • Part A: 4 months (Baseline to Month 4); Part B: 8 months (Month 4 to Month 12)	0.00% 0/90 • Part A: 4 months (Baseline to Month 4); Part B: 8 months (Month 4 to Month 12)	0.00% 0/152 • Part A: 4 months (Baseline to Month 4); Part B: 8 months (Month 4 to Month 12)
Cardiac disorders Cardiac failure congestive	1.1% 1/92 • Number of events 1 • Part A: 4 months (Baseline to Month 4); Part B: 8 months (Month 4 to Month 12)	0.00% 0/90 • Part A: 4 months (Baseline to Month 4); Part B: 8 months (Month 4 to Month 12)	0.00% 0/152 • Part A: 4 months (Baseline to Month 4); Part B: 8 months (Month 4 to Month 12)
Vascular disorders Peripheral vascular disorder	1.1% 1/92 • Number of events 1 • Part A: 4 months (Baseline to Month 4); Part B: 8 months (Month 4 to Month 12)	0.00% 0/90 • Part A: 4 months (Baseline to Month 4); Part B: 8 months (Month 4 to Month 12)	0.00% 0/152 • Part A: 4 months (Baseline to Month 4); Part B: 8 months (Month 4 to Month 12)
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	1.1% 1/92 • Number of events 1 • Part A: 4 months (Baseline to Month 4); Part B: 8 months (Month 4 to Month 12)	1.1% 1/90 • Number of events 1 • Part A: 4 months (Baseline to Month 4); Part B: 8 months (Month 4 to Month 12)	0.00% 0/152 • Part A: 4 months (Baseline to Month 4); Part B: 8 months (Month 4 to Month 12)
Injury, poisoning and procedural complications Subdural heamatoma	0.00% 0/92 • Part A: 4 months (Baseline to Month 4); Part B: 8 months (Month 4 to Month 12)	1.1% 1/90 • Number of events 1 • Part A: 4 months (Baseline to Month 4); Part B: 8 months (Month 4 to Month 12)	0.00% 0/152 • Part A: 4 months (Baseline to Month 4); Part B: 8 months (Month 4 to Month 12)
Nervous system disorders seizure	0.00% 0/92 • Part A: 4 months (Baseline to Month 4); Part B: 8 months (Month 4 to Month 12)	1.1% 1/90 • Number of events 1 • Part A: 4 months (Baseline to Month 4); Part B: 8 months (Month 4 to Month 12)	0.00% 0/152 • Part A: 4 months (Baseline to Month 4); Part B: 8 months (Month 4 to Month 12)
Infections and infestations Sepsis	0.00% 0/92 • Part A: 4 months (Baseline to Month 4); Part B: 8 months (Month 4 to Month 12)	1.1% 1/90 • Number of events 1 • Part A: 4 months (Baseline to Month 4); Part B: 8 months (Month 4 to Month 12)	0.00% 0/152 • Part A: 4 months (Baseline to Month 4); Part B: 8 months (Month 4 to Month 12)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Adenocarcinoma gastric	0.00% 0/92 • Part A: 4 months (Baseline to Month 4); Part B: 8 months (Month 4 to Month 12)	1.1% 1/90 • Number of events 1 • Part A: 4 months (Baseline to Month 4); Part B: 8 months (Month 4 to Month 12)	0.00% 0/152 • Part A: 4 months (Baseline to Month 4); Part B: 8 months (Month 4 to Month 12)
Infections and infestations pneumonia	0.00% 0/92 • Part A: 4 months (Baseline to Month 4); Part B: 8 months (Month 4 to Month 12)	1.1% 1/90 • Number of events 1 • Part A: 4 months (Baseline to Month 4); Part B: 8 months (Month 4 to Month 12)	0.00% 0/152 • Part A: 4 months (Baseline to Month 4); Part B: 8 months (Month 4 to Month 12)
Injury, poisoning and procedural complications Infusion related reaction	0.00% 0/92 • Part A: 4 months (Baseline to Month 4); Part B: 8 months (Month 4 to Month 12)	1.1% 1/90 • Number of events 1 • Part A: 4 months (Baseline to Month 4); Part B: 8 months (Month 4 to Month 12)	0.00% 0/152 • Part A: 4 months (Baseline to Month 4); Part B: 8 months (Month 4 to Month 12)
Gastrointestinal disorders abdominal pain upper	0.00% 0/92 • Part A: 4 months (Baseline to Month 4); Part B: 8 months (Month 4 to Month 12)	1.1% 1/90 • Number of events 1 • Part A: 4 months (Baseline to Month 4); Part B: 8 months (Month 4 to Month 12)	0.00% 0/152 • Part A: 4 months (Baseline to Month 4); Part B: 8 months (Month 4 to Month 12)
Injury, poisoning and procedural complications rib fracture	0.00% 0/92 • Part A: 4 months (Baseline to Month 4); Part B: 8 months (Month 4 to Month 12)	1.1% 1/90 • Number of events 1 • Part A: 4 months (Baseline to Month 4); Part B: 8 months (Month 4 to Month 12)	0.00% 0/152 • Part A: 4 months (Baseline to Month 4); Part B: 8 months (Month 4 to Month 12)
Endocrine disorders Goitre	0.00% 0/92 • Part A: 4 months (Baseline to Month 4); Part B: 8 months (Month 4 to Month 12)	0.00% 0/90 • Part A: 4 months (Baseline to Month 4); Part B: 8 months (Month 4 to Month 12)	0.66% 1/152 • Number of events 1 • Part A: 4 months (Baseline to Month 4); Part B: 8 months (Month 4 to Month 12)
Gastrointestinal disorders Diverticulum	0.00% 0/92 • Part A: 4 months (Baseline to Month 4); Part B: 8 months (Month 4 to Month 12)	0.00% 0/90 • Part A: 4 months (Baseline to Month 4); Part B: 8 months (Month 4 to Month 12)	0.66% 1/152 • Number of events 1 • Part A: 4 months (Baseline to Month 4); Part B: 8 months (Month 4 to Month 12)
Gastrointestinal disorders Small intestinal obstruction	0.00% 0/92 • Part A: 4 months (Baseline to Month 4); Part B: 8 months (Month 4 to Month 12)	0.00% 0/90 • Part A: 4 months (Baseline to Month 4); Part B: 8 months (Month 4 to Month 12)	0.66% 1/152 • Number of events 1 • Part A: 4 months (Baseline to Month 4); Part B: 8 months (Month 4 to Month 12)
General disorders Chest pain	0.00% 0/92 • Part A: 4 months (Baseline to Month 4); Part B: 8 months (Month 4 to Month 12)	0.00% 0/90 • Part A: 4 months (Baseline to Month 4); Part B: 8 months (Month 4 to Month 12)	0.66% 1/152 • Number of events 1 • Part A: 4 months (Baseline to Month 4); Part B: 8 months (Month 4 to Month 12)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant melanoma in situ	0.00% 0/92 • Part A: 4 months (Baseline to Month 4); Part B: 8 months (Month 4 to Month 12)	0.00% 0/90 • Part A: 4 months (Baseline to Month 4); Part B: 8 months (Month 4 to Month 12)	0.66% 1/152 • Number of events 1 • Part A: 4 months (Baseline to Month 4); Part B: 8 months (Month 4 to Month 12)
Nervous system disorders Ischaemic stroke	0.00% 0/92 • Part A: 4 months (Baseline to Month 4); Part B: 8 months (Month 4 to Month 12)	0.00% 0/90 • Part A: 4 months (Baseline to Month 4); Part B: 8 months (Month 4 to Month 12)	0.66% 1/152 • Number of events 1 • Part A: 4 months (Baseline to Month 4); Part B: 8 months (Month 4 to Month 12)