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CompletedNCT03455543RELIEFUpdated Jul 15, 2020Results posted

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

An interventional study of Active Provant Therapy System and Inactive (sham) Provant Therapy System in Diabetic Neuropathy Peripheral, sponsored by Regenesis Biomedical, Inc.. Completed at 18 sites in United States. Open to participants aged 22 Years to 80 Years. Per ClinicalTrials.gov, last updated 2020-07-15.

Sponsored by Regenesis Biomedical, Inc. · Not applicable, Interventional, and Treatment

Phase
Not applicable
Study type
Interventional
Enrollment
182
Allocation
Randomized
Ages
22 Years to 80 Years
Sex
All
01

Study 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.

Read the 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.

02

Conditions studied

  • Diabetic Neuropathy Peripheral
03

Who can participate

Ages eligible
22 Years to 80 Years
Sexes eligible
All
Accepts 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

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
04

Study design

Phase
Not applicable
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
182 participants (actual)

Study arms

  • Experimental
    Active Group

    Treatment with active Provant Therapy System

    Device: Active Provant Therapy System

  • Sham comparator
    Sham Group

    Treatment with in-active (sham) Provant Therapy System

    Device: Inactive (sham) Provant Therapy System

Interventions

  • DeviceActive Provant Therapy System

    Treatment with active Provant Therapy System

  • DeviceInactive (sham) Provant Therapy System

    Treatment with inactive Provant Therapy System

05

What researchers measure

Primary outcomes

  1. 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

Secondary outcomes

  1. 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

  2. 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.

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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

Other outcomes

  1. 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

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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

06

Results

Posted Mar 9, 2020

Participant flow

Part A: Randomized Treatment (17 Weeks)
Participant flow — Part A: Randomized Treatment (17 Weeks)
MilestoneActive GroupSham GroupOpen-label Extension Group (Part B)
Started92900
Completed81830
Not completed1170
Withdrew: Adverse event250
Withdrew: Withdrawal by subject720
Withdrew: Physician decision200
Part B: Open-label Extension (24 Weeks)
Participant flow — Part B: Open-label Extension (24 Weeks)
MilestoneActive GroupSham GroupOpen-label Extension Group (Part B)
Started00152
Completed00115
Not completed0037
Withdrew: Adverse event003
Withdrew: Withdrawal by subject0020
Withdrew: Lack of efficacy007
Withdrew: Lost to follow-up004
Withdrew: Out of window for visits002
Withdrew: Device interfered with home speakers001

Outcome measures

PrimaryChange 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
Reported as:
Mean · units on a scale
Change in Pain Intensity
units on a scaleActive GroupSham Group
Change in Pain Intensity-1.47 ± 1.845-1.25 ± 2.018
SecondaryPatients 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
Reported as:
Count of participants · Participants
Patients With 2 Point or 30% Reduction in Pain at 4 Months
ParticipantsActive GroupSham Group
Patients With 2 Point or 30% Reduction in Pain at 4 Months2826
SecondaryPatient 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.
Reported as:
Count of participants · Participants
Patient Global Impression at 4 Months
ParticipantsActive GroupSham Group
Much Worse12
Minimally Worse311
No Change2428
Minimally Improved3723
Much Improved1620
Very Much Improved33
Not reported83
SecondaryTime 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
Reported as:
Count of participants · Participants
Time to 30% or 2-point Reduction in NPRS, Whichever Comes First, Through 4 Months
ParticipantsActive GroupSham Group
Week 143
Week 41818
Week 83227
Week 124334
Week 174540
SecondaryChange 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
Reported as:
Mean · units on a scale
Change in Neuropathy Related Quality of Life (NeuroQoL) Between Baseline and End of Treatment at 4 Months.
units on a scaleActive GroupSham Group
(1) Pain-1.66 (-2.22 to -1.11)-1.52 (-2.13 to -0.91)
(2) Lost/Reduced Feeling-1.03 (-1.67 to -0.40)-1.42 (-2.16 to -0.68)
(3) Diffuse Sensory Motor Symptoms-0.92 (-1.53 to -0.30)-0.79 (-1.48 to -0.09)
(4) Restrictions in Activities of Daily Living-1.66 (-2.38 to -0.93)-2.38 (-3.16 to -1.60)
(5) Disruptions in Social Relationships-1.31 (-1.99 to -0.62)-1.99 (-2.70 to -1.29)
(6) Emotional Distress-1.12 (-1.68 to -0.55)-1.63 (-2.33 to -0.93)
SecondaryChange 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
Reported as:
Mean · mmHg
Change is Skin Perfusion Pressure (SPP) for Baseline to End of Treatment at 4 Months
mmHgActive GroupSham Group
Dorsal - Left-0.25 ± 34.223.27 ± 33.82
Dorsal - Right-0.74 ± 35.182.93 ± 25.83
Plantar - Left6.37 ± 27.72-1.84 ± 28.87
Plantar - Right2.12 ± 21.05-2.51 ± 23.66
SecondaryChanges 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
Reported as:
Mean · m/s (velocity)
Changes in Nerve Conduction Studies of Velocity Between Baseline and End of Treatment at 4 Months.
m/s (velocity)Active GroupSham Group
Velocity (uv) - Left-4.15 ± 20.45-5.12 ± 22.25
Velocity (uv) - Right-1.11 ± 18.18-5.06 ± 20.94
SecondaryChanges 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
Reported as:
Mean · Temperature in degrees C
Changes in Quantitative Sensory Testing (QST) Between Baseline and End of Treatment at 4 Months.
Temperature in degrees CActive GroupSham Group
Cold - Right0.57 ± 3.32-0.21 ± 3.07
Cold - Left0.08 ± 3.250.02 ± 2.85
Warm - Right-0.58 ± 3.70-0.54 ± 4.07
Warm - Left-0.53 ± 4.250.01 ± 4.41
Pain - Right-0.29 ± 3.21-0.75 ± 3.10
Pain - Left-0.62 ± 3.23-0.23 ± 2.97
Other pre-specifiedExploratory 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
Reported as:
Mean · Hours
Exploratory Endpoint: Changes in the Work Productivity and Activity Impairment Questionnaire (WPAIQ) (Questions 2-4)
HoursActive GroupSham Group
Work hours missed in past 7 days due to DN0.12 ± 2.960.33 ± 1.89
Work hours missed in past 7 days not due to DN0.60 ± 9.172.61 ± 9.38
Hours worked in past 7 days-0.48 ± 10.62-2.11 ± 20.80
Other pre-specifiedExploratory 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
Reported as:
Mean · nerve fiber density in fibers/mm
Exploratory Endpoint: Changes in Intraepidermal Nerve Fiber Density (IENFD) at the Distal Thigh and Distal Leg - Part A
nerve fiber density in fibers/mmActive GroupSham Group
Right Distal Leg-0.12 ± 1.600.73 ± 2.33
Right Distal Thigh0.64 ± 2.931.68 ± 2.63
Other pre-specifiedExploratory 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
Reported as:
Mean · units on a scale
Exploratory Endpoint: Change in Pain Intensity During Part B
units on a scaleActive GroupSham Group
Exploratory Endpoint: Change in Pain Intensity During Part B-2.96 ± 2.382.49 ± 2.38
Other pre-specifiedExploratory 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
Reported as:
Mean · m/s (velocity)
Exploratory Endpoint: Changes in Nerve Conduction Studies of Velocity During Part B
m/s (velocity)Active GroupSham Group
Velocity (m/s) - Left-11.9 ± 26.0-8.64 ± 24.7
Velocity (m/s) - Right-9.48 ± 19.5-6.31 ± 22.9
Other pre-specifiedExploratory 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
Reported as:
Mean · units on a scale
Exploratory Endpoint: Change in Neuropathy Related Quality of Life (NeuroQoL) During Part B
units on a scaleActive GroupSham Group
(1) Pain-3.14 ± 2.33-2.88 ± 3.19
(2) Lost/Reduced Feeling-2.42 ± 2.99-1.96 ± 4.07
(3) Diffuse Sensory Motor-1.58 ± 2.78-1.04 ± 3.41
(4) Restrictions in Activities-2.67 ± 3.61-2.14 ± 4.85
(5) Distruptions in Social Relationships-2.25 ± 3.73-1.73 ± 3.96
(6) Emotional Distress-1.60 ± 3.81-1.79 ± 3.58
SecondaryChanges 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
Reported as:
Mean · uv (amplitude)
Changes in Nerve Conduction Studies of Amplitude Between Baseline and End of Treatment at 4 Months.
uv (amplitude)Active GroupSham Group
Amplitude (m/s) - Left1.27 ± 9.961.36 ± 11.63
Amplitude (m/s) - Right1.95 ± 10.271.03 ± 9.91
Other pre-specifiedExploratory 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
Reported as:
Mean · uv (amplitude) and m/s (velocity)
Exploratory Endpoint: Changes in Nerve Conduction Studies of Amplitude During Part B
uv (amplitude) and m/s (velocity)Active GroupSham Group
Amplitude (uv) - Left5.28 ± 14.44.42 ± 14.6
Amplitude (uv) - Right6.0 ± 15.34.28 ± 14.2
Other pre-specifiedExploratory 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
Reported as:
Mean · units on a scale
Exploratory Endpoint: Changes in the Work Productivity and Activity Impairment Questionnaire (WPAIQ) (Questions 5-6)
units on a scaleActive GroupSham Group
Effect of DN on work in past 7 days-0.40 ± 1.89-0.61 ± 3.01
Effect on daily activities in past 7 days-0.67 ± 2.19-0.59 ± 2.70
Other pre-specifiedExploratory 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
Reported as:
Mean · nerve fiber density in fibers/mm
Exploratory Endpoint: Changes in Intraepidermal Nerve Fiber Density (IENFD) at the Distal Thigh and Distal Leg - Part B
nerve fiber density in fibers/mmOpen-label Extension Group (Part B)
Right Distal Leg.22 ± 2.17
Right Distal Thigh1.09 ± 2.94

Adverse events

Collected over Part A: 4 months (Baseline to Month 4); Part B: 8 months (Month 4 to Month 12). Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Active Group (Part A)0/92 (0%)5/92 (5.4%)0/92 (0%)
Sham Group (Part A)0/90 (0%)6/90 (6.7%)0/90 (0%)
Open-label Extension Group (Part B)57/152 (37.5%)5/152 (3.3%)0/152 (0%)
Most frequent serious events
Showing 10 of 19
Most frequent serious events
EventActive Group (Part A)Sham Group (Part A)Open-label Extension Group (Part B)
Chronic obstructive pulmonary diseaseRespiratory, thoracic and mediastinal disorders1/921/900/152
Subdural heamatomaInjury, poisoning and procedural complications0/921/900/152
seizureNervous system disorders0/921/900/152
SepsisInfections and infestations0/921/900/152
Adenocarcinoma gastricNeoplasms benign, malignant and unspecified (incl cysts and polyps)0/921/900/152
pneumoniaInfections and infestations0/921/900/152
Infusion related reactionInjury, poisoning and procedural complications0/921/900/152
abdominal pain upperGastrointestinal disorders0/921/900/152
rib fractureInjury, poisoning and procedural complications0/921/900/152
PancreatitisGastrointestinal disorders1/920/900/152

Baseline characteristics

Age, Continuous
Age, Continuous(years)Active GroupSham GroupTotal
Mean62.27 ± 10.2162.17 ± 9.3362.22 ± 9.76
Sex: Female, Male
Sex: Female, Male(Participants)Active GroupSham GroupTotal
Female504292
Male424890
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)Active GroupSham GroupTotal
Hispanic or Latino121527
Not Hispanic or Latino8075155
Unknown or Not Reported000
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Active GroupSham GroupTotal
American Indian or Alaska Native011
Asian314
Native Hawaiian or Other Pacific Islander000
Black or African American151429
White7473147
More than one race011
Unknown or Not Reported000
Region of Enrollment
Region of Enrollment(participants)Active GroupSham GroupTotal
United States9290182
07

Study locations

18 sites
  • Physician's Research Group
    Mesa, Arizona 85206, United States
  • Valley Clinical Research
    Northridge, California 91325, United States
  • Northern California Research
    Sacramento, California 95821, United States
  • Diabetes Research Center
    Tustin, California 92780, United States
  • Mountain View Clinical Research
    Denver, Colorado 80209, United States
  • Lake Internal Medicine Associates
    Eustis, Florida 32726, United States
  • Clinical Physiology Associates
    Fort Myers, Florida 33912, United States
  • Spotlight Research Center
    Miami, Florida 33176, United States
  • Clinical Research of Central Florida
    Winter Haven, Florida 33880, United States
  • River Birch Research Alliance, LLC
    Blue Ridge, Georgia 30514, United States
  • MediSphere Medical Research Center, LLC
    Evansville, Indiana 47714, United States
  • Heartland Research Associate, LLC
    Wichita, Kansas 67207, United States
  • Healthcare Research Network
    Hazelwood, Missouri 63042, United States
  • The Center for Pharmaceutical Research, LLC
    Kansas City, Missouri 64114, United States
  • Palm Research Center
    Las Vegas, Nevada 89128, United States
  • Great Lakes Medical Resarch
    Westfield, New York 14787, United States
  • Wake Family Medicine, PC
    Cary, North Carolina 27513, United States
  • Rainier Clinical Research
    Renton, Washington 98057, United States
08

References and documents

Study documents

  • Study protocol · Jul 17, 2018
  • Statistical analysis plan · Nov 7, 2018

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No

09

Registry details

Key details

Study ID
NCT03455543
Lead sponsor
Regenesis Biomedical, Inc.
Responsible party
Sponsor
First posted
Mar 6, 2018
Start date
Mar 26, 2018
Primary completion
Nov 14, 2018
Completion
Jul 18, 2019
Results posted
Mar 9, 2020
Last update
Jul 15, 2020

Oversight

FDA-regulated drug
No
FDA-regulated device
Yes
View the source record on ClinicalTrials.gov ↗

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