Using Cannabidiol to Treat Diabetic Peripheral Neuropathy of the Feet

Study Overview
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Brief Summary
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The purpose of the study is to evaluate whether PG-DN-20WS is a better pain reliever in patients with diabetic neuropathic pain of the feet than a placebo.

Detailed Description
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Subjects will be enrolled in the study for a maximum of 43 days, including an optional 14-day screening period, 28 days of active product administration, and followed by a post-treatment follow-up within 1 day. The primary objective of this study is: To evaluate the safety of PG-DN-20WS for the treatment of painful DPN of the feet compared to a placebo control, including emergence of suicidal thoughts. The secondary objectives of this study are: To evaluate the impact of PG-DN-20WS on subject's neuropathic pain, anxiety, and sleep quality compared to a placebo control. To evaluate the impact of PG-DN-20WS on the subject's impression of their response to the treatment compared to a placebo control.

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

Conditions
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Diabetic Peripheral Neuropathic Pain

Intervention / Treatment
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* Drug: CBD
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject is at least 21 years of age; Subject has a diagnosis of diabetic neuropathic pain of the feet determined by the subject's primary care physician or related health care provider. Subject has a mean pain scale score of ≥ 5 recorded in the 7 days prior to randomization. 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. 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. If subject is currently taking gabapentin, pregabalin, or duloxetine, subject must be willing to and completes a 7-day washout of these medications prior to randomization. Subject has not taken any NSAIDs and/or acetaminophen for at least 2 days prior to randomization. Subject is willing to provide his/her written informed consent to participate in the study as stated in the informed consent document. Subject is willing to use an electronic diary to enter trial information for 29 days. Exclusion Criteria: Subject is pregnant or lactating; Subject has an allergy to cannabis, the Cannabaceae plant family (e.g., hemp, hops), palmitoylethanolamide, or terpenes; Subject has a known allergy to active or inert ingredients of the investigational product; 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)); 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; Subject currently resides in the state of Nebraska, Idaho, Iowa, or South Dakota. Subject is currently being treated with antibiotics for sinus, throat, or lung infections; Subject has shortness of breath associated with allergies; Subject has uncontrolled asthma; Subject has a fever and/or productive cough; Subject has unstable angina, uncontrolled hypertension; Subject currently or has a history of congestive heart failure; Subject has any other unstable medical condition; Subject has a personal or family history of schizophrenia; Subject has a personal history or currently has suicidal ideation or attempted suicide; Subject has a major neurological disorder, such as dementia, Parkinson's disease, cognitive impairment, epilepsy, history of traumatic brain injury/head injury, and seizures. Subject has taken pharmaceutical pain medicine of any kind, or has taken a NSAID and/or acetaminophen, within 2 days of randomization. Subject has taken gabapentin, pregabalin, or duloxetine within 7 days prior to randomization or is unwilling to stop these medications. Subject has an allergy to, or has an intolerance to, NSAIDs or acetaminophen. Subject is currently taking any form of opioids. Subject has a history of substance or alcohol abuse. Subject has clinically significant illness, including cardiovascular disorders. 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. Subject does not have access to a smart phone or does not know how to use a smart phone application.

Ages Eligible for Study
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Minimum Age: 21 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

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
Interventional Model Description: There are 2 groups in this trial: interventional group (active drug) and control group (placebo).
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CBD<br>Subject will receive a 28-day supply of 20 mg CBD sublingual tablets to be taken 3 times a day for 28 days. | Drug: CBD<br>* A water-soluble sublingual tablet containing 20 mg of CBD.<br>|
| Placebo Comparator: Placebo Control<br>A placebo sublingual tablet to be taken three times a day for 28 days. | Drug: Placebo<br>* An inactive compound.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of treatment-related adverse events as assessed by CTCAE v4.0 | To evaluate the safety of PG-DN-20WS 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. | Four Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain as assessed by Numerical Pain Rating Scale (NPRS) | To evaluate the impact of PG-DN-20WS 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. | Four Weeks | 
| Anxiety as assessed by the Zung Self-Rating Anxiety Scale (SAS) | To evaluate the impact of PG-DN-20WS on the subject's anxiety as assessed by the Zung Self-Rating Anxiety Scale (SAS). Subjects are given scores from 1-4 based on their responses to the survey, where a higher global score indicates a more severe form of anxiety and a lower global score indicates either a less severe form of anxiety or no anxiety presented by the subject. | Four Weeks | 
| Sleep Quality as assessed by Pittsburgh Sleep Quality Index (PSQI) | To evaluate the impact of PG-DN-20WS on the subject's anxiety as assessed by the Pittsburgh Sleep Quality Index (PSQI). Subjects are given scores from 0-3 based on their responses to the survey, where a higher global score indicates poor sleep quality and a lower global score indicates good sleep quality reported by the subject. | Four Weeks | 
| Subject's Response to Treatment as assessed by Patient's Global Impression of Change (PGIC) | To evaluate the impact of PG-DN-20WS 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. | Four Weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cannabidiol, CBD, DPN, Diabetic Peripheral Neuropathy