Diabetic Neuropathic Pain Relief, 6 Weeks Dosage Sublingual Water-soluble CBD/PEA

Diabetic Peripheral Neuropathic Pain Clinical Trial

Official title:

A Randomized, Double-Blind, Placebo-Controlled Trial Using Cannabidiol and Palmitoylethanolamide for the Treatment of Painful Diabetic Peripheral Neuropathy of the Feet

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05766969
• Other study ID #: The DIA/NPR-6 Study
• Status: Not yet recruiting
• Phase: Phase 1/Phase 2
• Start date: June 5, 2023
• Est. completion date: December 5, 2023

Study information

• Verified date: May 2022
• Source: Pure Green Pharmaceuticals Inc.
• Contact: Debra Kimless, MD
• Phone: 248-920-8761
• Email: dkimlessmd[@]pgpharma.co
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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:

• To evaluate the impact of PGP-010-50-1 on subject's painful diabetic neuropathic pain (pDNP), anxiety, and sleep quality compared to a placebo control.

• To evaluate the impact of PGP-010-50-1 on the subject's impression of their response to the treatment compared to a placebo control.

The secondary objectives of this study are:

• To evaluate the safety of PGP-010-50-1 for the treatment of painful diabetic peripheral neuropathy (DPN) of the feet compared to a placebo control

• To evaluate PGP-010-50-1 on liver function.

• To evaluate PGP-010-50-1 on Hbg A1C

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 52
• Est. completion date: December 5, 2023
• Est. primary completion date: December 5, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 21 Years to 65 Years

Eligibility

Inclusion Criteria:

1. Subject is at least 21 years of age.

2. Subject is or under the age of 65 years of age.

3. Subject has a primary health care provider and gives permission for PG Pharma to contact the primary health care provider.

4. Subject has a diagnosis of diabetic neuropathic pain of the feet .

5. Subject has a mean pain scale score of = 4 and = 8 recorded localized to the foot in the 7 days prior to randomization.

6. If female, the subject is postmenopausal (> 1 year), surgically sterile (> 3 months), had a hysterectomy, or is currently using 2 effective forms of birth control.

7. Subject has not taken marijuana (cannabis) in any form, chemicals or extracts or foods or beverages or topical creams, lotions, gels, patches containing marijuana (cannabinoids, or and cannabis derivatives) including synthetic marijuana and/or CBD for at least 14 days prior to this study, and agrees to not take marijuana (cannabis) in any form, chemicals or extracts or foods or beverages or topical creams, lotions, gels, patches containing marijuana (cannabinoids, or and cannabis derivatives) including synthetic marijuana and/or CBD while participating in this study.

8. Subject is willing to provide his/her written informed consent to participate in the study as stated in the informed consent document.

9. Subject has a smart phone, knows how to use it, and is willing to use it for accessing and interacting with an electronic diary to enter trial information for the duration of the study - 57 days. (up to 14-day screening period and 42 days active dosing and 1 day post dosing.

Exclusion Criteria:

1. Subject is pregnant or lactating.

2. Subject is unwilling to utilize two forms of birth control with partner.

3. Male subject is unwilling to agree to not donate sperm from the time of dosing until 90 days after dosing of study drug.

4. Subject has an allergy to cannabis, the Cannabaceae plant family (e.g., hemp, hops), palmitoylethanolamide, or terpenes.

5. Subject has a known allergy to active or inert ingredients of the investigational product.

6. Subject is taking a concomitant medication or treatment that would complicate use or interpretation of the study drug's effects (examples include: Cannabis or any cannabinoid products; Any drug or herbal product that influences the endocannabinoid system (ECS)). However, subjects are allowed to continue gabapentin and pregabalin medications, if the subject still meets the pain scale inclusion criteria, evidencing lack of effectiveness of their concomitant pain medication.

7. Subjects on SNRIs or SSRIs.

8. Subject is taking marijuana (cannabis) in any form, chemicals or extracts or foods or beverages or topical creams, lotions, gels, patches containing marijuana (cannabinoids, or and cannabis derivatives) including synthetic marijuana and/or CBD for at least 14 days prior to this study, and does not promise that they will not take marijuana (cannabis) in any form, chemicals or extracts or foods or beverages or topical creams, lotions, gels, patches containing marijuana (cannabinoids, or and cannabis derivatives) including synthetic marijuana and/or CBD while participating in this study;

9. Subject has shortness of breath.

10. Subject has uncontrolled asthma.

11. Subject has a fever and/or productive cough.

12. Subject has unstable angina, uncontrolled hypertension.

13. Subject currently or has a history of congestive heart failure.

14. Subject meets any DSM-V criteria for current, major psychiatric illness, including but not limited to: bipolar disorder, major depressive disorder, psychosis, or substance abuse disorder.

15. Subject has a personal or family history of schizophrenia.

16. Subject has a personal history or currently has suicidal ideation or attempted suicide.

17. Subject has a major neurological disorder, such as dementia, Parkinson's disease, cognitive impairment, epilepsy, history of traumatic brain injury/head injury, and seizures.

18. Subject has a history of multiple sclerosis.

19. Subject is currently taking any form of opioids.

20. Subject has a history of substance or alcohol abuse.

21. Subject has clinically significant illness, including cardiovascular disorders.

22. Subject has any condition in which the investigator believes will confound the data of the study or could put the subject at risk of harm.

23. Subject does not have access to a smart phone or does not know how to use a smart phone application.

24. Subject is not within 30 miles of a Quest Diagnostics laboratory.

25. The skin under the tongue or anywhere in the oral cavity is not intact.

26. Subject has abnormal liver function test results.

27. Subject has a history of abnormal liver dysfunction or liver pathology.

Related Conditions & MeSH terms

• Diabetic Peripheral Neuropathic Pain
• Neuralgia

Intervention

Drug:
• CBD/PEA
A water-soluble sublingual tablet containing 10/50 mg of CBD/PEA.
• Placebo
An inactive compound.

Locations

Country	Name	City	State
United States	Pure Green Pharmaceuticals Inc.	Southfield	Michigan

Sponsors (1)

Lead Sponsor	Collaborator
Pure Green Pharmaceuticals Inc.

Country where clinical trial is conducted

United States, 

References & Publications (15)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

* Note: There are 15 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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
Secondary	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
Secondary	Subject's Response to Treatment as assessed by Patient's Global Impression of Change (PGIC)	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