Diabetic Neuropathy Peripheral Clinical Trial
— RELIEFOfficial title:
A Multi-Center, Double-Blind, Sham-Controlled, Randomized Trial of Dual Field PEMF Therapy [Provant® Therapy System] in Lower Extremity Painful Diabetic Distal Symmetric Peripheral Neuropathy (DSPN) (The RELIEF Trial)
Verified date | July 2020 |
Source | Regenesis Biomedical, Inc. |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
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.
Status | Completed |
Enrollment | 182 |
Est. completion date | July 18, 2019 |
Est. primary completion date | November 14, 2018 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 22 Years to 80 Years |
Eligibility |
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 |
Country | Name | City | State |
---|---|---|---|
United States | River Birch Research Alliance, LLC | Blue Ridge | Georgia |
United States | Wake Family Medicine, PC | Cary | North Carolina |
United States | Mountain View Clinical Research | Denver | Colorado |
United States | Lake Internal Medicine Associates | Eustis | Florida |
United States | MediSphere Medical Research Center, LLC | Evansville | Indiana |
United States | Clinical Physiology Associates | Fort Myers | Florida |
United States | Healthcare Research Network | Hazelwood | Missouri |
United States | The Center for Pharmaceutical Research, LLC | Kansas City | Missouri |
United States | Palm Research Center | Las Vegas | Nevada |
United States | Physician's Research Group | Mesa | Arizona |
United States | Spotlight Research Center | Miami | Florida |
United States | Valley Clinical Research | Northridge | California |
United States | Rainier Clinical Research | Renton | Washington |
United States | Northern California Research | Sacramento | California |
United States | Diabetes Research Center | Tustin | California |
United States | Great Lakes Medical Resarch | Westfield | New York |
United States | Heartland Research Associate, LLC | Wichita | Kansas |
United States | Clinical Research of Central Florida | Winter Haven | Florida |
Lead Sponsor | Collaborator |
---|---|
Regenesis Biomedical, Inc. |
United States,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Other | 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. |
Baseline to 4 Months | |
Other | 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. |
Baseline to Month 4 | |
Other | 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. | Baseline through 12 months | |
Other | 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. | Baseline to Month 12 | |
Other | 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 |
Baseline to Month 12 | |
Other | 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. | Baseline to Month 12 | |
Other | 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. |
Baseline to 4 Months | |
Other | 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. |
Baseline to Month 12 | |
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). | Baseline through 4 months | |
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). |
Baseline to 4 months | |
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. | Baseline through 4 months. | |
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. | Through 4 months | |
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. |
Baseline to 4 months | |
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 |
Baseline to 4 months | |
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. | Baseline to 4 Months | |
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. |
Baseline to 4 months | |
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. | Baseline to 4 Months |
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