Painful Peripheral Diabetic Neuropathy
Conditions
Brief summary
Evaluate the effectiveness of the Provant Therapy System compared to sham on pain sensitivity and nervous system response to various qualities of experimentally induced pain in the upper and lower extremities of subjects with painful peripheral diabetic neuropathy.
Detailed description
This is a multi-center, randomized, double-blind, sham-controlled crossover clinical trial conducted on subjects with painful peripheral diabetic neuropathy. Eligible subjects will include those between 22 and 80 years of age with Type 2 diabetes having persistent pain, numbness, tingling, and/or burning in at least one foot. Pain threshold, tolerance to thermal stimuli and pressure response to the induced pain stimuli will be measured at three time points using five standardized experimental pain measures: baseline, after a single 30 minute treatment with active PEMF or sham treatment and after a second 30 minute treatment with active PEMF or sham treatment. Eligible subjects with painful peripheral diabetic neuropathy will undergo Diabetic Screening (Nerve Conduction Velocity, Skin Perfusion Pressure, Ankle-Brachial Index, and Vibratory Testing) in the index foot prior to randomization. Following the Diabetic Screening tests, subjects will return to the research center for the Enrollment/Randomization Visit and complete measures of pain by completing the Brief Pain Inventory (BPI) and functional assessments. Subjects will then be randomly assigned to one of the two groups; control (sham) or experimental (active) device by a research assistant blinded to the device status. Patients will also be randomly assigned to the sequence order of experimental induced pain tests. The ischemic pain testing (SMET) will always be conducted last. Patients will return to the research center within 7 days after the Enrollment/Randomization Visit where they will be crossed over to the other treatment assignment and be randomly assigned to the sequence order of experimental induced pain tests on the same extremity as previously randomized.
Interventions
DEVICEProvant
Sponsors
Regenesis Biomedical, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
22 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. Subject age is greater than or equal to 22 years and less than 80 years of age. 2. Subject has documented Type 2 diabetes. 3. Subject's BMI ≤ 38. 4. Subject has peripheral diabetic neuropathy with pain, numbness, tingling, and/or burning in at least one foot. 5. Subject is in pain Phase 2, 3, or 4 (Appendix B). 6. Subject is willing to forego smoking during the Enrollment Visit and Visit 3 (Crossover) for 4 hours prior to and through the duration of testing (\ 5 hours). 7. Subject is willing and able to give written informed consent and to comply with all parts of the study protocol. 8. Female subjects must be post-menopausal, surgically sterile, abstinent, or practicing (or agree to practice) an effective method of birth control if they are sexually active for the duration of the study. (Effective methods of birth control include prescription hormonal contraceptives, intrauterine devices, double-barrier methods, and/or male partner sterilization). 9. Subject is able to eat in the morning prior to the induced pain tests and provide a meal/snacks for themselves during the day to maintain blood sugar levels.
Exclusion criteria
1. Subject has current pain other than their painful peripheral diabetic neuropathy. 2. Subject has a concomitant medical condition that, in the opinion of the investigator, would confound the ability to conduct induced pain testing in the upper and lower extremities. 3. Subject has taken prescription opioids for their pain within 30 days of the Screening Visit or 6 weeks of Screening for long acting medications. 4. Subject has used topical capsaicin within 30 days of the Screening Visit. 5. Subject has Type 1 diabetes. 6. Subject is in pain Phase 1 or 5 (Appendix B). 7. Subject has an active, open ulcer on either lower extremity of arterial, venous or mixed disease origin. 8. Subject has peripheral arterial disease as determined by an Ankle-Brachial Index (ABI) of \<0.5 or \> 1.4. See Appendix C for details on obtaining the ABI. 9. Subject has venous insufficiency classified by the Venous Insufficiency Classification System (CEAP) of grade C6. See Appendix D for description of the venous insufficiency grading. 10. Subject has an unhealed surgery on the legs, feet, arms or hands. 11. Subject has smoked within 4 hours of the Screening Visit. 12. Subject has received any investigational drug or device within 30 days or 5 half-lives of the drug, whichever is longer, prior to the Screening Visit or is enrolled in another clinical trial. 13. Subject has used systemic corticosteroids within 2 months of the Screening Visit. 14. Subject has a history of a solid tumor that is not in complete remission for greater than 2 years other than successfully treated non-metastatic basal cell or squamous cell carcinomas of the skin in the treatment area. 15. Subject has a serious psychosocial co-morbidity. 16. Subject has a self-reported history of drug or alcohol abuse, within one year prior to the Screening Visit. 17. Subject has an implanted pacemaker, defibrillator, neurostimulator, spinal cord stimulator, bone stimulator, cochlear implant, or other implanted device with an implanted metal lead(s). 18. Subject is currently pregnant. 19. Subject has been previously treated with the PROVANT Therapy System within 30 days of the Enrollment Visit. 20. Subject is unwilling or unable to follow study instructions.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Upper Extremity - Pain Sensitivity to Various Experimentally Induced Pain Stimuli | 4 weeks | Response data by induced pain stimuli after the initial treatment with the study device in the upper extremity. The stimuli / test was determined to either favor sham or favor Provant Therapy. This included a total of 20 stimuli/tests (comparing pre-treatment to post initial treatment results) as follows: Cuff Pain Threshold (greater decrease favored), Cuff Pain Tolerance (smaller increase favored), Cuff Pressure Threshold (greater decrease favored), Pressure Tolerance (greater increase favored), Mechanical Pain Threshold (greater decrease favored), Biothesiomety (greater decrease favored) on the forearm, palm, thumb, index finger, middle finger, ring finger and pinky finger, Heat Tolerance (greater decrease favored), Cold Tolerance (greater decrease favored), Pain (greater increase favored), Time to Pain (greater increase favored), Pain Tolerance Grip Strength (greater increase favored) and Final Pain (greater decrease favored). |
| Lower Extremity - Pain Sensitivity to Various Experimentally Induced Pain Stimuli | 4 weeks | Response data by induced pain stimuli after the initial treatment with the study device in the upper extremity. The stimuli / test was determined to either favor sham or favor Provant Therapy. This included a total of 20 stimuli/tests (comparing pre-treatment to post initial treatment results) as follows: Cuff Pain Threshold (greater decrease favored), Cuff Pain Tolerance (smaller increase favored), Cuff Pressure Threshold (greater decrease favored), Pressure Tolerance (greater increase favored), Mechanical Pain Threshold (greater decrease favored), Biothesiomety (greater decrease favored) on the forearm, palm, thumb, index finger, middle finger, ring finger and pinky finger, Heat Tolerance (greater decrease favored), Cold Tolerance (greater decrease favored), Pain (greater increase favored), Time to Pain (greater increase favored), Pain Tolerance Grip Strength (greater increase favored) and Final Pain (greater decrease favored). . |
Countries
United States
Participant flow
Pre-assignment details
Due to an error in the randomization for this study, results are based upon data only for the Initial Treatment population (those subjects treated with either active or sham at the Enrollment Visit). Data from the cross-over was not included since the majority of subjects were not crossed-over to the other treatment.
Participants by arm
| Arm | Count |
|---|---|
| Sham of Provant Sham of Provant Therapy System
Due to an error in the randomization for this study, results are based upon data only for the Initial Treatment population (those subjects treated with either active or sham at the Enrollment Visit). Data from the cross-over was not included since the majority of subjects were not crossed-over to the other treatment. | 22 |
| Active Provant Active Provant Treatment
Due to an error in the randomization for this study, results are based upon data only for the Initial Treatment population (those subjects treated with either active or sham at the Enrollment Visit). Data from the cross-over was not included since the majority of subjects were not crossed-over to the other treatment. | 19 |
| Total | 41 |
Baseline characteristics
| Characteristic | Sham of Provant | Active Provant | Total |
|---|---|---|---|
| Age, Continuous | 63 years STANDARD_DEVIATION 12.14 | 63.8 years STANDARD_DEVIATION 12.38 | 63.4 years STANDARD_DEVIATION 12.1 |
| BMI | 30.6 kg/m^2 STANDARD_DEVIATION 4.89 | 29.4 kg/m^2 STANDARD_DEVIATION 5.17 | 30 kg/m^2 STANDARD_DEVIATION 5 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 11 Participants | 7 Participants | 18 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 11 Participants | 11 Participants | 22 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 3 Participants | 5 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 19 Participants | 16 Participants | 35 Participants |
| Region of Enrollment United States | 22 participants | 19 participants | 41 participants |
| Sex: Female, Male Female | 14 Participants | 9 Participants | 23 Participants |
| Sex: Female, Male Male | 8 Participants | 10 Participants | 18 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 22 | 0 / 19 |
| serious Total, serious adverse events | 0 / 22 | 0 / 19 |
Outcome results
Primary
Lower Extremity - Pain Sensitivity to Various Experimentally Induced Pain Stimuli
Response data by induced pain stimuli after the initial treatment with the study device in the upper extremity. The stimuli / test was determined to either favor sham or favor Provant Therapy. This included a total of 20 stimuli/tests (comparing pre-treatment to post initial treatment results) as follows: Cuff Pain Threshold (greater decrease favored), Cuff Pain Tolerance (smaller increase favored), Cuff Pressure Threshold (greater decrease favored), Pressure Tolerance (greater increase favored), Mechanical Pain Threshold (greater decrease favored), Biothesiomety (greater decrease favored) on the forearm, palm, thumb, index finger, middle finger, ring finger and pinky finger, Heat Tolerance (greater decrease favored), Cold Tolerance (greater decrease favored), Pain (greater increase favored), Time to Pain (greater increase favored), Pain Tolerance Grip Strength (greater increase favored) and Final Pain (greater decrease favored). .
Time frame: 4 weeks
Population: Includes subjects in the Initial Treatment Group (Those subjects treated with either Provant or Sham at the Enrollment Visit)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sham of Provant | Lower Extremity - Pain Sensitivity to Various Experimentally Induced Pain Stimuli | 16 Number of tests favoring arm/group |
| Active Provant | Lower Extremity - Pain Sensitivity to Various Experimentally Induced Pain Stimuli | 4 Number of tests favoring arm/group |
Primary
Upper Extremity - Pain Sensitivity to Various Experimentally Induced Pain Stimuli
Response data by induced pain stimuli after the initial treatment with the study device in the upper extremity. The stimuli / test was determined to either favor sham or favor Provant Therapy. This included a total of 20 stimuli/tests (comparing pre-treatment to post initial treatment results) as follows: Cuff Pain Threshold (greater decrease favored), Cuff Pain Tolerance (smaller increase favored), Cuff Pressure Threshold (greater decrease favored), Pressure Tolerance (greater increase favored), Mechanical Pain Threshold (greater decrease favored), Biothesiomety (greater decrease favored) on the forearm, palm, thumb, index finger, middle finger, ring finger and pinky finger, Heat Tolerance (greater decrease favored), Cold Tolerance (greater decrease favored), Pain (greater increase favored), Time to Pain (greater increase favored), Pain Tolerance Grip Strength (greater increase favored) and Final Pain (greater decrease favored).
Time frame: 4 weeks
Population: Due to an error in the randomization for this study, results are based upon data only for the Initial Treatment population (those subjects treated with either active or sham at the Enrollment Visit). Data from the cross-over was not included since the majority of subjects were not crossed-over to the other treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sham of Provant | Upper Extremity - Pain Sensitivity to Various Experimentally Induced Pain Stimuli | 6 Number of tests favoring arm/group |
| Active Provant | Upper Extremity - Pain Sensitivity to Various Experimentally Induced Pain Stimuli | 14 Number of tests favoring arm/group |