CBD for Pain Reduction and Opioid Use After Ankle and Tibia Fracture ORIF

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to evaluate the effects of administering CBD to control post-operative pain in patients undergoing ankle fracture open reduction and internal fixation, tibial plafond (pilon) open reduction and internal fixation, tibial shaft repair (open reduction internal fixation or intramedullary nail fixation), or tibial plateau open reduction and internal fixation. Secondly, the purpose is to evaluate the effectiveness of CBD in comparison with opioid therapy for post-operative pain.

Official Title
-----------------
The Use of Cannabidiol (CBD) in Pain Reduction and Opioid Use After Ankle and Tibia Fracture Open Reduction and Internal Fixation. A Double-Blind, Randomized Control Study

Conditions
-----------------
Ankle Fractures, Tibia Fracture

Intervention / Treatment
-----------------
* Drug: CBD
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients undergoing an ankle fracture open reduction and internal fixation (medial malleolus, lateral malleolus, posterior malleolus, and/or syndesmosis repair), tibial plafond (pilon) open reduction and internal fixation, tibial shaft repair (open reduction internal fixation and intramedullary nail fixation), or tibial plateau open reduction and internal fixation Patients ages 18-75, inclusive Female patients must be currently practicing effective forms of two types of birth control, which are defined as those, alone or in combination, that result in a low failure rate (less than 1% per year) when used consistently and correctly Male patients must be using an effective form of contraception Exclusion Criteria: Legally incompetent or mentally impaired (e.g., minors, Alzheimer's subjects, dementia, etc.) Younger than 18 years of age Older than 75 years of age Any patient considered a vulnerable subject: pregnant women or fetuses, children, cognitively impaired adults, prisoners History of cannabis abuse or dependence History of coagulation abnormalities and thromboembolic disease or current abnormal coagulation test values History of stroke or acute coronary syndromes within 3 months before surgery Abnormal coagulation profile Renal failure (serum creatinine > 250 μmol/L [2.83 mg/dL]) or liver cirrhosis Patients that have been on pre-operative opioid management for any reason Patients meeting the DSM-V for major psychiatric illness, such as bipolar disorder Patients diagnosed with major depression, psychosis, or substance abuse disorder Patients with current or a history of suicidal ideation Breastfeeding females Patients with clinically significant illness, including cardiovascular disorders Clinically significant lab abnormalities Abnormal LFTs Patients with major neurological disorders, such as dementia, Parkinson's disease, cognitive impairment, epilepsy, history of traumatic brain/head injury, or seizures Patients with moderate (Child-Pugh B) and severe hepatic impairment (Child-Pugh C). Patients taking moderate or strong inhibitors of CYP3A4 and CYP2C19 concomitantly Patients taking strong CYP3A4 and CYP2C19 inducers concomitantly

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Cannabidiol (CBD)<br> | Drug: CBD<br>* 25mg CBD ODTs (orally disintegrating tablet), with instructions to take CBD tablets t.i.d. (total of 50mg per dose t.i.d.) to be administered with routine post-operative pain management<br>|
| Placebo Comparator: Control<br> | Drug: Placebo<br>* Visually indistinguishable placebo ODTs, with instructions to take two tablets t.i.d., to be administered with routine post-operative pain management<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Score on Pain Visual Analog Scale (VAS) | Pain severity scores at rest will be assessed by use of a visual analog scale (VAS; total range = 0-10; 0 = no pain, 10 = worst pain imaginable) | Day 2 Post-Surgery | 
| Score on Pain Visual Analog Scale (VAS) | Pain severity scores at rest will be assessed by use of a visual analog scale (VAS; total range = 0-10; 0 = no pain, 10 = worst pain imaginable) | Day 7 Post-Surgery | 
| Score on Pain Visual Analog Scale (VAS) | Pain severity scores at rest will be assessed by use of a visual analog scale (VAS; total range = 0-10; 0 = no pain, 10 = worst pain imaginable) | Day 14 Post-Surgery | 
| Level of Nausea Using VAS | Any nausea experienced by the patients will be recorded by use of a VAS (total range = 0-10; 0 = no nausea, 10 = worst nausea imaginable) | Day 2 Post-Surgery | 
| Level of Nausea Using VAS | Any nausea experienced by the patients will be recorded by use of a VAS (total range = 0-10; 0 = no nausea, 10 = worst nausea imaginable) | Day 7 Post-Surgery | 
| Level of Nausea Using VAS | Any nausea experienced by the patients will be recorded by use of a VAS (total range = 0-10; 0 = no nausea, 10 = worst nausea imaginable) | Day 14 Post-Surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CBD Consumption | Patient self report | Day 2 Post-Surgery | 
| CBD Consumption | Patient self report | Day 7 Post-Surgery | 
| CBD Consumption | Patient self report | Day 14 Post-Surgery | 
| Opioid Consumption | Patient self report | Day 2 Post-Surgery | 
| Opioid Consumption | Patient self report | Day 7 Post-Surgery | 
| Opioid Consumption | Patient self report | Day 14 Post-Surgery | 
| Patient Satisfaction Score | Patients will record their satisfaction with their management, on a 0-10 scale. The higher the score, the higher the satisfaction. | Day 14 Post-Surgery | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Cannabidiol