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

Primary Purpose

Tibial Fractures, Fibula Fracture, Knee Fracture

Status

Withdrawn

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Palmitoylethanolamide

Placebo

About this trial

This is an interventional treatment trial for Tibial Fractures focused on measuring Palmitoylethanolamide, Open reduction and internal fixation (ORIF) Surgery, Postoperative Pain, Inflammation, Reduce Opioid Consumption

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

UC Irvine Medical Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Palmitoylethanolamide

Placebo

Arm Description

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

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

Outcomes

Primary Outcome Measures

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 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

Secondary Outcome Measures

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.

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

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.

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.

Post-Surgical Complications

Any complications following surgery

Medication Adverse Events

Any adverse events to study drug and post-surgical medications given at discharge

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.

Full Information

NCT ID

NCT05317676

First Posted

February 22, 2022

Last Updated

May 5, 2023

Sponsor

University of California, Irvine

Collaborators

GE Nutrients Inc. (Gencor)

1. Study Identification

Unique Protocol Identification Number

NCT05317676

Brief Title

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

2. Study Status

Record Verification Date

May 2023

Overall Recruitment Status

Withdrawn

Why Stopped

Sponsor suspending temporarily.

Study Start Date

May 2023 (Anticipated)

Primary Completion Date

December 2024 (Anticipated)

Study Completion Date

December 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

University of California, Irvine

Collaborators

GE Nutrients Inc. (Gencor)

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Tibial Fractures, Fibula Fracture, Knee Fracture

Keywords

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

Investigator

Allocation

Randomized

Enrollment

0 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Palmitoylethanolamide

Arm Type

Active Comparator

Arm Description

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

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

Palmitoylethanolamide

Other Intervention Name(s)

PEA, GenCor

Intervention Description

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

Intervention Name(s)

Placebo

Intervention Description

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

Primary Outcome Measure Information:

Title

3 month post-surgical Opioid use Questionnaire

Description

Questionnaire (during call) asking patient for list of medications taken in last 2 days and cross referencing with opioid prescription in chart

Time Frame

3 months

Title

3 month post-surgical NSAID use Questionnaire

Description

Questionnaire (during call) asking patient for list of medications taken in last 2 days and cross referencing with NSAID prescription in chart

Time Frame

3 months

Secondary Outcome Measure Information:

Title

Pain Scores

Description

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.

Time Frame

3 months

Title

Pain Interference

Description

Time Frame

3 months

Title

Average Pain Scores

Description

Time Frame

3 months

Title

Functional Status

Description

Time Frame

3 months

Title

Post-Surgical Complications

Description

Any complications following surgery

Time Frame

3 months

Title

Medication Adverse Events

Description

Any adverse events to study drug and post-surgical medications given at discharge

Time Frame

3 months

Title

Average Pain Interference

Description

Time Frame

3 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Ariana Nelson, MD

Organizational Affiliation

Associate Clinical Professor

Official's Role

Principal Investigator

Facility Information:

Facility Name

UC Irvine Medical Center

City

Orange

State/Province

California

ZIP/Postal Code

92868

Country

United States

12. IPD Sharing Statement

Citations:

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Citation

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

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