Clinical trial NCT05317676: Effect of Palmitoylethanolamide on Reducing Opioid Consumption for Below Knee Fracture Fixation
Official title: Effect of Palmitoylethanolamide on Reducing Opioid Consumption for Postoperative Pain and Inflammation Following Below Knee Fracture Fixation: A Pilot Study.
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Tibial Fractures
Fibula Fracture
Knee Fracture
Keywords: Palmitoylethanolamide
Open reduction and internal fixation (ORIF) Surgery
Postoperative Pain
Inflammation
Reduce Opioid Consumption
Lead sponsor: University of California, Irvine
Sponsor class: OTHER
Collaborators: name: GE Nutrients Inc. (Gencor)
First posted: 2022-04-08
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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

Eligibility criteria: 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

Primary outcomes:
measure: 3 month post-surgical Opioid use Questionnaire
timeFrame: 3 months
measure: 3 month post-surgical NSAID use Questionnaire
timeFrame: 3 months
Secondary outcomes:
measure: Pain Scores
timeFrame: 3 months
measure: Pain Interference
timeFrame: 3 months
measure: Average Pain Scores
timeFrame: 3 months
measure: Functional Status
timeFrame: 3 months
measure: Post-Surgical Complications
timeFrame: 3 months
measure: Medication Adverse Events
timeFrame: 3 months
measure: Average Pain Interference
timeFrame: 3 months
Other outcomes:
Locations:
city: Orange
country: United States
facility: UC Irvine Medical Center
state: California
Study officials:
affiliation: Associate Clinical Professor
name: Ariana Nelson, MD
role: PRINCIPAL_INVESTIGATOR
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