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

NCT05317676 | Withdrawn Phase 2 DMC FDA Drug

• 1 other identifier: 2020-6007
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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.

Conditions

Tibial Fractures; Fibula Fracture; Knee Fracture

Keywords

Palmitoylethanolamide; Open reduction and internal fixation (ORIF) Surgery; Postoperative Pain; Inflammation; Reduce Opioid Consumption

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (7)

• Pain Scores

  3 months

• Pain Interference

  3 months

• Average Pain Scores

  3 months

• Functional Status

  3 months

• Post-Surgical Complications

  3 months

Study Arms (2)

Palmitoylethanolamide

ACTIVE COMPARATOR

300 mg PEA twice a day for a total of 600 mg PEA daily 2-month supply upon discharge

Drug: Palmitoylethanolamide

Placebo

PLACEBO COMPARATOR

1 placebo tablet twice a day for a total of 2 tablet placebo daily 2-month supply upon discharge

Drug: Placebo

Interventions

Palmitoylethanolamide DRUG

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).

Also known as: PEA, GenCor

Palmitoylethanolamide

Placebo DRUG

2-month supply of placebo will be given upon discharge. Placebo will taken twice a day in conjunction with discharge medications (opioid and NSAIDs).

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of California, Irvine: lead
• GE Nutrients Inc. (Gencor): collaborator

Study Sites (1)

UC Irvine Medical Center

Orange, California, 92868, United States

Location

Related Publications (13)

• Artukoglu BB, Beyer C, Zuloff-Shani A, Brener E, Bloch MH. Efficacy of Palmitoylethanolamide for Pain: A Meta-Analysis. Pain Physician. 2017 Jul;20(5):353-362.

  PMID: 28727699 BACKGROUND

• Grotenhermen F. Cannabinoids and the endocannabinoid system. Cannabinoids.2006;1:10-14.

  BACKGROUND

• Martin-Sanchez E, Furukawa TA, Taylor J, Martin JL. Systematic review and meta-analysis of cannabis treatment for chronic pain. Pain Med. 2009 Nov;10(8):1353-68. doi: 10.1111/j.1526-4637.2009.00703.x. Epub 2009 Sep 1.

  PMID: 19732371 BACKGROUND

• Cabral GA, Griffin-Thomas L. Emerging role of the cannabinoid receptor CB2 in immune regulation: therapeutic prospects for neuroinflammation. Expert Rev Mol Med. 2009 Jan 20;11:e3. doi: 10.1017/S1462399409000957.

  PMID: 19152719 BACKGROUND

• Calignano A, La Rana G, Giuffrida A, Piomelli D. Control of pain initiation by endogenous cannabinoids. Nature. 1998 Jul 16;394(6690):277-81. doi: 10.1038/28393.

  PMID: 9685157 BACKGROUND

• Calignano A, La Rana G, Piomelli D. Antinociceptive activity of the endogenous fatty acid amide, palmitylethanolamide. Eur J Pharmacol. 2001 May 11;419(2-3):191-8. doi: 10.1016/s0014-2999(01)00988-8.

  PMID: 11426841 BACKGROUND

• Esposito E, Paterniti I, Mazzon E, Genovese T, Di Paola R, Galuppo M, Cuzzocrea S. Effects of palmitoylethanolamide on release of mast cell peptidases and neurotrophic factors after spinal cord injury. Brain Behav Immun. 2011 Aug;25(6):1099-112. doi: 10.1016/j.bbi.2011.02.006. Epub 2011 Feb 25.

  PMID: 21354467 BACKGROUND

• Luongo L, Guida F, Boccella S, Bellini G, Gatta L, Rossi F, de Novellis V, Maione S. Palmitoylethanolamide reduces formalin-induced neuropathic-like behaviour through spinal glial/microglial phenotypical changes in mice. CNS Neurol Disord Drug Targets. 2013 Feb 1;12(1):45-54. doi: 10.2174/1871527311312010009.

  PMID: 23394524 BACKGROUND

• Scuderi C, Steardo L. Neuroglial roots of neurodegenerative diseases: therapeutic potential of palmitoylethanolamide in models of Alzheimer's disease. CNS Neurol Disord Drug Targets. 2013 Feb 1;12(1):62-9. doi: 10.2174/1871527311312010011.

  PMID: 23394526 BACKGROUND

• Nau R, Djukic M, Spreer A, Ribes S, Eiffert H. Bacterial meningitis: an update of new treatment options. Expert Rev Anti Infect Ther. 2015;13(11):1401-23. doi: 10.1586/14787210.2015.1077700. Epub 2015 Aug 18.

  PMID: 26293166 BACKGROUND

• Gabrielsson L, Mattsson S, Fowler CJ. Palmitoylethanolamide for the treatment of pain: pharmacokinetics, safety and efficacy. Br J Clin Pharmacol. 2016 Oct;82(4):932-42. doi: 10.1111/bcp.13020. Epub 2016 Jun 29.

  PMID: 27220803 BACKGROUND

• COBURN AF, GRAHAM CE, HANINGER J. The effect of egg yolk in diets on anaphylactic arthritis (passive Arthus phenomenon) in the guinea pig. J Exp Med. 1954 Nov 1;100(5):425-35. doi: 10.1084/jem.100.5.425.

  PMID: 13211905 BACKGROUND

• Hesselink JM. Evolution in pharmacologic thinking around the natural analgesic palmitoylethanolamide: from nonspecific resistance to PPAR-alpha agonist and effective nutraceutical. J Pain Res. 2013 Aug 8;6:625-34. doi: 10.2147/JPR.S48653. eCollection 2013.

  PMID: 23964161 BACKGROUND

MeSH Terms

Conditions

Tibial Fractures; Fibula Fractures; Knee Fractures; Pain, Postoperative; Inflammation

Interventions

palmidrol

Condition Hierarchy (Ancestors)

Fractures, Bone; Wounds and Injuries; Leg Injuries; Knee Injuries; Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Pain; Neurologic Manifestations; Signs and Symptoms

Study Officials

• Ariana Nelson, MD

  Associate Clinical Professor

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Clinical Professor

Study Record Dates

• First Submitted: February 22, 2022
• First Posted: April 8, 2022
• Study Start: May 1, 2023
• Primary Completion: December 1, 2024
• Study Completion: December 1, 2025
• Last Updated: May 9, 2023

Record last verified: 2023-05

Locations

US (1)