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

NCT ID: NCT05317676

Last Updated: 2023-05-09

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

WITHDRAWN

Clinical Phase

PHASE2

Study Classification

INTERVENTIONAL

Study Start Date

2023-05-31

Study Completion Date

2025-12-31

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

Conditions

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Tibial Fractures Fibula Fracture Knee Fracture

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Investigators

Study Groups

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Palmitoylethanolamide

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

Group Type ACTIVE_COMPARATOR

Palmitoylethanolamide

Intervention Type 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).

Placebo

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

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type 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).

Interventions

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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).

Intervention Type 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).

Intervention Type DRUG

Other Intervention Names

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PEA GenCor

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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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GE Nutrients Inc. (Gencor)

UNKNOWN

Sponsor Role collaborator

University of California, Irvine

OTHER

Sponsor Role lead

Responsible Party

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Ariana M. Nelson

Associate Clinical Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Ariana Nelson, MD

Role: PRINCIPAL_INVESTIGATOR

Associate Clinical Professor

Locations

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UC Irvine Medical Center

Orange, California, United States

Site Status

Countries

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United States

References

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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.

Reference Type BACKGROUND
PMID: 28727699 (View on PubMed)

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

Reference Type 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.

Reference Type BACKGROUND
PMID: 19732371 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 19152719 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 9685157 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 11426841 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 21354467 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 23394524 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 23394526 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 26293166 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 27220803 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 13211905 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 23964161 (View on PubMed)

Other Identifiers

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2020-6007

Identifier Type: -

Identifier Source: org_study_id

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