Nociceptive Pain Fiber Response

Study Overview
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Brief Summary
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This study is designed to evaluate the effectiveness of the Provant Therapy System in improving localized nerve growth and skin perfusion in subjects with painful peripheral diabetic neuropathy of the foot.

Detailed Description
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The study is multi-site, randomized, double-blind, sham-controlled study of the safety and efficacy of multi-dose Provant therapy to evaluate neuronal and vascular response in the treatment of subjects with painful peripheral diabetic neuropathy. Subjects will be randomized in a 2:1 ratio to receive therapy with an active device or an identical inactive sham device. Subjects will treat at home twice daily for 60 days after which they will return to the clinic for final evaluations. Subjects will be evaluated at the research center for a Baseline/Enrollment visit and again at Day 61 where assessments for safety, concomitant medications, Sympathetic Skin Response (SSR), Nerve Conduction Velocity (NCV), Skin Perfusion Pressures (SPP), and Skin Biopsy will be completed. Subjects will be contacted via telephone at Day 14, Day 28 and Day 42 to assess adherence, safety, and concomitant medications. Subjects will also complete a Response to Study Device form which will capture their daily pain score.

Official Title
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A Multi-Center, Randomized, Sham-Controlled, Double-Blind Study of Pulsed Electromagnetic Field (PEMF) Therapy to Evaluate Small Fiber Nerve Growth and Function in Subjects With Painful Peripheral Diabetic Neuropathy

Conditions
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Painful Peripheral Diabetic Neuropathy

Intervention / Treatment
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* Device: Provant Therapy System


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject age is greater than or equal to 22 years and less than 80 years of age. Subject has documented Type 2 diabetes. Subject has an HgbA1c > 7% and < 10%. Subject has peripheral diabetic neuropathy with pain, numbness, tingling, and/or burning in at least one foot confirmed by a positive provocative sign and a positive Tinel's sign. If both feet are involved, the one with the greatest severity will be selected as the index foot. Subject is in pain Phase 2, 3, or 4 (Appendix C). Subject is willing and able to give written informed consent and to comply with all parts of the study protocol including diary entries. 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). Exclusion Criteria: Subject has Type 1 diabetes. Subject is in pain Phase 1 or 5 (Appendix C). Subject has an active, open ulcer on either lower extremity of arterial, venous or mixed disease origin. Subject has peripheral arterial disease as determined by an Ankle-Brachial Index (ABI) of >1.40 or < 0.80. See Appendix E for details on obtaining the ABI. NOTE: If the difference in the brachial pulse pressure between the right and left arms is > 10 mmHg, the subject will not be eligible for enrollment and will be referred to a cardiologist for further evaluation. Subject has venous insufficiency classified by the Venous Insufficiency Classification System (CEAP) of grades C3, C4, C5, or C6. See Appendix F for description of the venous insufficiency grading. Subject has undergone decompression surgery on the index foot to treat peripheral neuropathy within 2 years of the Screening Visit. Subject requires or anticipates the need for surgery of any type during the 60 day treatment period. Subject is a smoker or has been a smoker within one year of the Screening Visit. Subject has a total foot thickness (plantar surface to mid-dorsal surface) of > 6 centimeters. Subject anticipates travelling over the course of the 60 day treatment period. 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. Subject has undergone any local injection into the index foot within 30 days prior to the Screening Visit or within 6 weeks prior to the Screening Visit for long acting lidocaine injection products. Subject has used systemic corticosteroids within 2 months of the Screening Visit. Subject has a history of any uncontrolled medical illness that in the investigator's judgment places the subject at unacceptable risk for receipt of PEMF therapy. Subject has a history of malignancy within the past five years other than successfully treated non-metastatic basal cell or squamous cell carcinomas of the skin in the treatment area and/or localized in situ carcinoma of the cervix. Subject has a serious psychosocial co-morbidity. Subject has a history of drug or alcohol abuse, as confirmed by urine drug screen, within one year prior to the Screening Visit. Subject has an implanted pacemaker, defibrillator, neurostimulator, spinal cord stimulator, bone stimulator, cochlear implant, or other implanted device with an implanted metal lead(s). Subject is currently pregnant or planning on becoming pregnant prior to Day 60. Subject has been previously treated with the PROVANT Therapy System. Subject is unwilling or unable to follow study instructions, or comply with the treatment regimen and study visits.

Ages Eligible for Study
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Minimum Age: 22 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Sham of Provant<br>Sham of Provant | Device: Provant Therapy System<br> <br> |
| Other: Active Treatment<br>Active Provant Treatment | Device: Provant Therapy System<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in Small Nerve Fiber Density by Assessment of a Skin Biopsy Comparing Baseline to Day 60 | The mean percent change in intraepidermal nerve fiber density mean values for mean nerve fibers per millimeter squared from baseline to Day 60 was calculated for each treatment group (value at 60 days minus value at baseline). | 60 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pain, Diabetic Neuropathy, Pulsed Electromagnetic Energy Field, PEMF, PPDN