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

May 5, 2023 updated by: Ariana M. Nelson, University of California, Irvine

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

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.

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

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

Study Type

Interventional

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Orange, California, United States, 92868
        • UC Irvine Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
3 month post-surgical Opioid use Questionnaire
Time Frame: 3 months
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
Time Frame: 3 months
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
Time Frame: 3 months
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
Time Frame: 3 months
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
Time Frame: 3 months
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
Time Frame: 3 months
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
Time Frame: 3 months
Any complications following surgery
3 months
Medication Adverse Events
Time Frame: 3 months
Any adverse events to study drug and post-surgical medications given at discharge
3 months
Average Pain Interference
Time Frame: 3 months
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of California, Irvine

Collaborators

GE Nutrients Inc. (Gencor)

Investigators

  • Principal Investigator: Ariana Nelson, MD, Associate Clinical Professor

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

May 1, 2023

Primary Completion (Anticipated)

December 1, 2024

Study Completion (Anticipated)

December 1, 2025

Study Registration Dates

First Submitted

February 22, 2022

First Submitted That Met QC Criteria

March 30, 2022

First Posted (Actual)

April 8, 2022

Study Record Updates

Last Update Posted (Actual)

May 9, 2023

Last Update Submitted That Met QC Criteria

May 5, 2023

Last Verified

May 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2020-6007

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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