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The purpose of the study is to evaluate whether the DIA/NPR-6 is a better pain reliever in patients with diabetic neuropathic pain of the feet compared to placebo.
Subjects will be enrolled in the study for a maximum of 63 days, including an optional 14-day screening period, 42 days of active product administration, and followed by post-treatment blood work, EKG, and questionnaires within 24-hours following study treatment completion and a psychiatric and primary health care provider evaluation within 1 week of trial completion.
The primary objective of this study is:
The secondary objectives of this study are:
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| CBD/PEA | Experimental | Subject will receive a 42-day supply of 10/50 mg CBD/PEA sublingual tablets to be taken 3 times a day for 42 days. |
|
| Placebo Control | Placebo Comparator | A placebo sublingual tablet to be taken three times a day for 42 days. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| CBD/PEA | Drug | A water-soluble sublingual tablet containing 10/50 mg of CBD/PEA. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Pain as assessed by Numerical Pain Rating Scale (NPRS) | To evaluate the impact of DIA/NPR-6 on the subject's neuropathic pain as assessed by utilizing a Numeric Pain Rating Scale (NPRS). NPRS is from 0-10, where higher scores indicate worse pain, and lower scores indicate less pain reported by the subject. | Six Weeks |
| Pain as measured by the Brief Pain Inventory (BPI) | To evaluate the impact of DIA/NPR-6 on the subject's neuropathic pain as assessed by utilizing a Brief Pain Inventory (BPI) where patients will answer 15 questions regarding their pain. | Six Weeks |
| Anxiety as measured by the Self-Rating Anxiety Scale (SAS) | To evaluate the impact of DIA/NPR-6 on the subject's anxiety as assessed by the Self-Rating Anxiety Scale (SAS). Subjects will complete SAS prior to first dose and during post-treatment. | Six Weeks |
| Sleep as measured by the Pittsburg Sleep Quality Index (PSQI) | To evaluate the impact of DIA/NPR-6 on the subject's sleep as assessed by the Pittsburgh Sleep Quality Index (PSQI). Subjects will be evaluated pre- and post-treatment. The PSQI produces a global score and 6 subscales, Subjective Sleep Quality, Sleep Latency, Sleep Duration, Habitual Sleep Efficiency, Sleep Disturbances, Use of Sleeping Medications, and Daytime Dysfunction. | Six Weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Incidence of treatment-related adverse events as assessed by CTCAE v4.0 | To evaluate the safety of DIA/NPR-6 for the treatment of painful DPN of the feet compared to a placebo control assessed by Common Terminology Criteria for Adverse Events (CTCAE) v4.0. | Six Weeks |
| Subject's Response to Treatment as assessed by Patient's Global Impression of Change (PGIC) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Debra Kimless, MD | Contact | 248-920-8761 | dkimlessmd@pgpharma.co | |
| Donna McLean | Contact | 248-800-6126 | dmclean@pgpharma.com |
| Name | Affiliation | Role |
|---|---|---|
| Debra Kimless, MD | Pure Green Pharmaceuticals Inc. | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Pure Green Pharmaceuticals Inc. | Southfield | Michigan | 48034 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 12577252 | Background | Quattrini C, Tesfaye S. Understanding the impact of painful diabetic neuropathy. Diabetes Metab Res Rev. 2003 Jan-Feb;19 Suppl 1:S2-8. doi: 10.1002/dmrr.360. | |
| 22608666 | Background | Callaghan BC, Cheng HT, Stables CL, Smith AL, Feldman EL. Diabetic neuropathy: clinical manifestations and current treatments. Lancet Neurol. 2012 Jun;11(6):521-34. doi: 10.1016/S1474-4422(12)70065-0. Epub 2012 May 16. |
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There are 2 groups in this trial: interventional group (active drug) and control group (placebo).
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Subjects will be randomized at a 2:1 ratio.
| Placebo | Drug | An inactive compound. |
|
To evaluate the impact of DIA/NPR-6 on the subject's impression of their response to the treatment compared to a placebo control as assessed by Patient's Global Impression of Change (PGIC). Subjects indicate their overall impression of their response to treatment on 0-10 scale, where a higher number represents the subject feeling worse than before the intervention, and a lower number represents the subject feeling better than before the intervention. |
| Six Weeks |
| 16608048 | Background | Argoff CE, Cole BE, Fishbain DA, Irving GA. Diabetic peripheral neuropathic pain: clinical and quality-of-life issues. Mayo Clin Proc. 2006 Apr;81(4 Suppl):S3-11. doi: 10.1016/s0025-6196(11)61474-2. |
| 25498300 | Background | Sadosky A, Mardekian J, Parsons B, Hopps M, Bienen EJ, Markman J. Healthcare utilization and costs in diabetes relative to the clinical spectrum of painful diabetic peripheral neuropathy. J Diabetes Complications. 2015 Mar;29(2):212-7. doi: 10.1016/j.jdiacomp.2014.10.013. Epub 2014 Nov 8. |
| 12766111 | Background | Gordois A, Scuffham P, Shearer A, Oglesby A, Tobian JA. The health care costs of diabetic peripheral neuropathy in the US. Diabetes Care. 2003 Jun;26(6):1790-5. doi: 10.2337/diacare.26.6.1790. |
| 24373831 | Background | Singh R, Kishore L, Kaur N. Diabetic peripheral neuropathy: current perspective and future directions. Pharmacol Res. 2014 Feb;80:21-35. doi: 10.1016/j.phrs.2013.12.005. Epub 2013 Dec 25. |
| 25843054 | Background | Wallace MS, Marcotte TD, Umlauf A, Gouaux B, Atkinson JH. Efficacy of Inhaled Cannabis on Painful Diabetic Neuropathy. J Pain. 2015 Jul;16(7):616-27. doi: 10.1016/j.jpain.2015.03.008. Epub 2015 Apr 3. |
| 11399676 | Background | Bridges D, Ahmad K, Rice AS. The synthetic cannabinoid WIN55,212-2 attenuates hyperalgesia and allodynia in a rat model of neuropathic pain. Br J Pharmacol. 2001 Jun;133(4):586-94. doi: 10.1038/sj.bjp.0704110. |
| 15140913 | Background | De Vry J, Denzer D, Reissmueller E, Eijckenboom M, Heil M, Meier H, Mauler F. 3-[2-cyano-3-(trifluoromethyl)phenoxy]phenyl-4,4,4-trifluoro-1-butanesulfonate (BAY 59-3074): a novel cannabinoid Cb1/Cb2 receptor partial agonist with antihyperalgesic and antiallodynic effects. J Pharmacol Exp Ther. 2004 Aug;310(2):620-32. doi: 10.1124/jpet.103.062836. Epub 2004 May 12. |
| 17296917 | Background | Abrams DI, Jay CA, Shade SB, Vizoso H, Reda H, Press S, Kelly ME, Rowbotham MC, Petersen KL. Cannabis in painful HIV-associated sensory neuropathy: a randomized placebo-controlled trial. Neurology. 2007 Feb 13;68(7):515-21. doi: 10.1212/01.wnl.0000253187.66183.9c. |
| 20805210 | Background | Ware MA, Wang T, Shapiro S, Robinson A, Ducruet T, Huynh T, Gamsa A, Bennett GJ, Collet JP. Smoked cannabis for chronic neuropathic pain: a randomized controlled trial. CMAJ. 2010 Oct 5;182(14):E694-701. doi: 10.1503/cmaj.091414. Epub 2010 Aug 30. |
| 23237736 | Background | Wilsey B, Marcotte T, Deutsch R, Gouaux B, Sakai S, Donaghe H. Low-dose vaporized cannabis significantly improves neuropathic pain. J Pain. 2013 Feb;14(2):136-48. doi: 10.1016/j.jpain.2012.10.009. Epub 2012 Dec 11. |
| 18403272 | Background | Wilsey B, Marcotte T, Tsodikov A, Millman J, Bentley H, Gouaux B, Fishman S. A randomized, placebo-controlled, crossover trial of cannabis cigarettes in neuropathic pain. J Pain. 2008 Jun;9(6):506-21. doi: 10.1016/j.jpain.2007.12.010. Epub 2008 Apr 10. |
| 19896326 | Background | Johnson JR, Burnell-Nugent M, Lossignol D, Ganae-Motan ED, Potts R, Fallon MT. Multicenter, double-blind, randomized, placebo-controlled, parallel-group study of the efficacy, safety, and tolerability of THC:CBD extract and THC extract in patients with intractable cancer-related pain. J Pain Symptom Manage. 2010 Feb;39(2):167-79. doi: 10.1016/j.jpainsymman.2009.06.008. Epub 2009 Nov 5. |
| 30157131 | Background | De Gregorio D, McLaughlin RJ, Posa L, Ochoa-Sanchez R, Enns J, Lopez-Canul M, Aboud M, Maione S, Comai S, Gobbi G. Cannabidiol modulates serotonergic transmission and reverses both allodynia and anxiety-like behavior in a model of neuropathic pain. Pain. 2019 Jan;160(1):136-150. doi: 10.1097/j.pain.0000000000001386. |