Effect of Palmitoylethanolamide on Reducing Opioid Consumption for Below Knee Fracture Fixation

Study Overview
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Brief Summary
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Palmitoylethanolamide (PEA), a non-psychoactive cannabis compound derived from peanuts, egg yolks, and soybeans, is an Endogenous FA Amide produced in the body as a biological response and a repair mechanism in chronic inflammation and chronic pain. In animal and clinical trials, PEA has also shown evidence of pain reduction, sleep improvement, and increased joint mobility and function with minimal side-effects. The study team intends to study whether the inclusion of PEA in conjunction with standard post-surgical medications can reduce pain and inflammation while decreasing the number of opioids needed.

Detailed Description
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According to the National Center for Health Statistics, the United States sees approximately 492,000 tibial fractures per year. Of that population, there are greater than 70,000 hospitalizations, 800,000 office visits, and 500,000 hospital days attributed annually. This does not include the approximately 250,000 proximal femur fractures that occur in the US annually, which is expected to double by 2050. There are also over 5 million ankle injuries in the US per year at a rate of approximately 187 ankle fractures per 100,000 people. To repair these below knee fractures, patients with severe cases often have an open reduction and internal fixation (ORIF) surgery to stabilize and heal the broken bone. On average, these patients are seen by physical therapy to determine their safety for going home and if they need any equipment like a walker or crutches. They are discharged with pain medications, such as analgesic opioids and stool softeners. These patients return to clinic in 2 weeks for follow up which involves an exam, suture removal, x-rays, and possibly weight bearing status update. They then return in 1 month for exam, x-rays, and weightbearing status. Finally they return at 3 months for exam, x-rays, and weightbearing status. The study team intends to study whether the inclusion of PEA in conjunction with standard post-surgical medications can reduce pain and inflammation while decreasing the number of opioids needed

Official Title
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Effect of Palmitoylethanolamide on Reducing Opioid Consumption for Postoperative Pain and Inflammation Following Below Knee Fracture Fixation: A Pilot Study.

Conditions
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Tibial Fractures, Fibula Fracture, Knee Fracture

Intervention / Treatment
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* Drug: Palmitoylethanolamide
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 years of age or older Has an isolated below knee orthopaedic injury without any neurovascular injury involvement Has an isolated active orthopaedic injury Females of childbearing potential must have a negative urine and blood pregnancy test at Screening and a negative urine pregnancy test on Day 1 before study drug is administered. Females must abstain from sex or use a highly effective method of contraception during the period from Screening to administration of study drug and for 30 days after the last dose of study medication. Standard acceptable methods include abstinence or the use of a highly effective method of contraception, including; hormonal contraception, diaphragm, cervical cap, vaginal sponge, condom with spermicide, vasectomy, intrauterine device. If females are of non-child bearing potential, they must be post-menopausal defined as: age > 55 with no menses within the past 12 months or history of hysterectomy, or history of bilateral oophorectomy, or bilateral tubal ligation. Exclusion Criteria: Less than 18 years of age Pregnant or Breastfeeding Allergic to cannabis History of chronic opioid use History of substance abuse History of chronic use of cannabis products of any kind Has multiple active orthopaedic injuries Has neurovascular injury associated with your orthopaedic injury History of a syndrome that causes chronic pain (i.e. fibromuscular dysplasia, complex pain syndrome) History of peripheral neuropathy History of diagnosed psychiatric illness ASA score of greater than 3 Clinically significant unstable medical condition, including but not limited to cardiovascular, neurologic, psychiatric, endocrine, hepatic, and renal disorders. Allergy to palmitoylethanolamide (PEA) or its derivatives such as soy or eggs AST/ALT ≥3x ULN and/or bilirubin ≥2x ULN at screening. Abnormal creatinine or renal function abnormalities. Have end stage organ failure (Cardiac, Renal, or Hepatic) Currently undergoing addiction/detoxification therapy

Ages Eligible for Study
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Minimum Age: 18 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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Palmitoylethanolamide<br>300 mg PEA twice a day for a total of 600 mg PEA daily 2-month supply upon discharge | Drug: Palmitoylethanolamide<br>* 2-month supply of PEA will be given upon discharge. 300mg will be taken twice a day in conjunction with discharge medications (opioid and NSAIDs).<br>* Other names: GenCor;|
| Placebo Comparator: Placebo<br>1 placebo tablet twice a day for a total of 2 tablet placebo daily 2-month supply upon discharge | Drug: Placebo<br>* 2-month supply of placebo will be given upon discharge. Placebo will taken twice a day in conjunction with discharge medications (opioid and NSAIDs).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 3 month post-surgical Opioid use Questionnaire | Questionnaire (during call) asking patient for list of medications taken in last 2 days and cross referencing with opioid prescription in chart | 3 months | 
| 3 month post-surgical NSAID use Questionnaire | Questionnaire (during call) asking patient for list of medications taken in last 2 days and cross referencing with NSAID prescription in chart | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain Scores | Pain scores using McGill Pain Questionnaire; minimum pain score: 0 (would not be seen in a person with true pain);maximum pain score: 78;The higher the pain score the greater the pain. | 3 months | 
| Pain Interference | Pain interference using PROMIS Pain Interference Survey; Each question usually has five response options ranging in value from one to five. To find the total raw score for a short form with all questions answered, sum the values of the response to each question. For example, for the adult 6-item form, the lowest possible raw score is 6; the highest possible raw score is 30.Locate the applicable score conversion table and use this table to translate the total raw score into a T-score for each participant. The T-score rescales the raw score into a standardized score with a mean of 50 and a standard deviation (SD) of 10 | 3 months | 
| Average Pain Scores | Pain scores using Brief Pain Inventory; 0-10 numerical rating scale used to measure three pain severity items: worst in the past month, average, and now, where 0=no pain and 10=pain as bad as you can imagine. | 3 months | 
| Functional Status | Functional status using PROMIS Physical Function Survey; The PF-10a is a 10-item questionnaire assessing current self-reported physical function. Raw scores range from 10 to 50 and can be translated into T-scores, with a mean of 50 and a standard deviation of 10, for comparison with the U.S. general population mean; for this study, all reported PF-10a scores are T-scores. | 3 months | 
| Post-Surgical Complications | Any complications following surgery | 3 months | 
| Medication Adverse Events | Any adverse events to study drug and post-surgical medications given at discharge | 3 months | 
| Average Pain Interference | Pain interference using Brief Pain Inventory; 0-10 numerical rating scale used to measure three pain severity items: worst in the past month, average, and now, where 0=no pain and 10=pain as bad as you can imagine. | 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Palmitoylethanolamide, Open reduction and internal fixation (ORIF) Surgery, Postoperative Pain, Inflammation, Reduce Opioid Consumption