ANZCTR - Registration

Please note the ANZCTR will be unattended from Friday 20 December 2024 for the holidays. The Registry will re-open on Tuesday 7 January 2025. Submissions and updates will not be processed during that time.

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Trial registered on ANZCTR

Registration number

ACTRN12619000418178p

Ethics application status

Submitted, not yet approved

Date submitted

18/02/2019

Date registered

14/03/2019

Date last updated

26/03/2019

Date data sharing statement initially provided

14/03/2019

Type of registration

Prospectively registered

Titles & IDs

Public title

Palmitoylethanolamide for the treatment of centralised chronic pain

Scientific title

Palmitoylethanolamide for the treatment of chronic nociplastic pain: a randomised double-blind placebo-controlled trial.

Secondary ID [1]

Nil known

Universal Trial Number (UTN)

U1111-1228-7941

Trial acronym

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Chronic Pain

Condition category

Condition code

Anaesthesiology

Pain management

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

Palmitoylethanolamide 300mg capsules. 300mg orally twice daily for 2 weeks then 600mg orally twice daily for further 24 weeks.

Patients will be reviewed at 3 months and 6 months and asked to bring in medications to monitor adherence.

Intervention code [1]

Treatment: Drugs

Comparator / control treatment

Placebo capsule containing lacose. one capsule orally twice daily for 2 weeks then two capsules orally twice daily for further 24 weeks.

Control group

Placebo

Outcomes

Primary outcome [1]

Mean pain interference as assessed by the Brief Pain Inventory (BPI)

Timepoint [1]

6 months post baseline

Secondary outcome [1]

Mean Pain Interference as measured by BPI

Timepoint [1]

3 months post baseline

Secondary outcome [2]

Average pain as measure by BPI

Timepoint [2]

3 months post baseline

Secondary outcome [3]

Average pain as measure by BPI

Timepoint [3]

6 months post baseline

Secondary outcome [4]

DASS21 score

Timepoint [4]

3 months post baseline

Secondary outcome [5]

DASS21 score

Timepoint [5]

6 months post baseline

Secondary outcome [6]

Pain Catastrophising Scale (PCS) score

Timepoint [6]

3 months post baseline

Secondary outcome [7]

PCS score

Timepoint [7]

6 months post baseline

Secondary outcome [8]

Patient Self Efficacy Questionnaire (PSEQ) score

Timepoint [8]

3 months post baseline

Secondary outcome [9]

PSEQ score

Timepoint [9]

6 months post baseline

Secondary outcome [10]

Global assessment of change

Timepoint [10]

3 months post baseline

Secondary outcome [11]

Global assessment of change

Timepoint [11]

6 months post baseline

Secondary outcome [12]

Change in daily opioid dose in oral morphine equivalents. The patients use of opioid medications be ascertained from a medication list. Dosing of opioid medications will converted to oral morphine equivalents (OME) using the Australian and New Zealand Collage of Anaesthetists Faculty of Pain Medicine Opioid Calculator . The change (increase or reduction) between baseline and 3 months time point.

Timepoint [12]

Baseline to 3 months post baseline

Secondary outcome [13]

Timepoint [13]

Baseline to 6 months post baseline

Secondary outcome [14]

Symptom Severity Score (SSS) from 2011 ACR Fibromyalgia Survey questionnaire

Timepoint [14]

3 months post baseline

Secondary outcome [15]

Symptom Severity Score (SSS) from 2011 ACR Fibromyalgia Survey questionnaire

Timepoint [15]

6 months post baseline

Eligibility

Key inclusion criteria

• Chronic pain at least 3 months duration AND
• Evidence of centralised pain/ neuroinflammatory response as evidenced by Symptom Severity Score (from Fibromyalgia Survey Score) greater than or equal to 7/12 AND
• Average pain intensity as measured by modified BPI greater than or equal to 5/10 (moderate or severe) AND
• Pain interference as measure by BPI greater than or equal to 5/10 (moderate or severe)

Minimum age

18 Years

Maximum age

No limit

Sex

Both males and females

Can healthy volunteers participate?

Key exclusion criteria

• Daily opioids > 120 OME
• Planned procedural intervention within 6 months
• Pre-study use of PEA
• Workers compensation or other ongoing compensation claim
• Major psychiatric disease (BPAD, Psychosis, PTSD)
• Pregnancy or breastfeeding
• Non-English speaking
• Cognitive impairment significant enough to impair informed consent

Study design

Purpose of the study

Treatment

Allocation to intervention

Randomised controlled trial

Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)

numbered containers

Methods used to generate the sequence in which subjects will be randomised (sequence generation)

Permuted block randomisation

Masking / blinding

Blinded (masking used)

Who is / are masked / blinded?

The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data

Intervention assignment

Parallel

Other design features

Phase

Phase 4

Type of endpoint/s

Efficacy

Statistical methods / analysis

Statistical analysis
Continuous outcomes will be assessed for normality using the SK test. Normal data will be presented as mean (SD) and analysed by Student T-test. Non-normal data will be presented as median (IQR) and assessed by Mann-Whitney U-test. Categorical data will be assessed by Chi-Squared test or Fisher’s exact test as appropriate.

Patients will be requested to complete the full 6 months of study drug therapy, and will be requested to complete follow up questionnaires regardless of compliance with use of study drug. Missing data will be filled using last data carried forward. Outcomes will be analysed in an intention to treat analysis, and an alpha of 0.01 will be used to determine statistical significance.

Sample size calculation.
Given a mean baseline pain interference of 7.0, and reductions in pain interference of 30% and 50% in the placebo and PEA groups respectively and an expected SD of 2.0, 100 patients will give 82.4% power with an alpha of 0.01.

Recruitment

Recruitment status

Not yet recruiting

Date of first participant enrolment

Anticipated

15/04/2019

Actual

Date of last participant enrolment

Anticipated

28/02/2020

Actual

Date of last data collection

Anticipated

29/08/2019

Actual

Sample size

Target

100

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

Recruitment hospital [1]

Sir Charles Gairdner Hospital - Nedlands

Recruitment postcode(s) [1]

6009 - Nedlands

Funding & Sponsors

Funding source category [1]

Charities/Societies/Foundations

Name [1]

ANZCA Research Foundation

Address [1]

630 St Kilda Rd, Melbourne VIC 3004

Country [1]

Australia

Funding source category [2]

Hospital

Name [2]

Sir Charles Gairdner Hospital

Address [2]

Hospital Ave Nedlands WA 6009

Country [2]

Australia

Primary sponsor type

Individual

Name

Daniel Ellyard

Address

Department of Pain Medicine
Sir Charles Gairdner Hospital
Nedlands WA 6009

Country

Australia

Secondary sponsor category [1]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Submitted, not yet approved

Ethics committee name [1]

Sir Charles Gairdner Osborne Park Health Care Group Human Research Ethics Committee

Ethics committee address [1]

Hospital Ave, Nedlands WA 6009

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

14/02/2019

Approval date [1]

Ethics approval number [1]

Summary

Brief summary

Chronic low level inflammation within the central nervous system (CNS) is increasingly being recognised as a potential contributor to many types of persistent pain. Through the activation of glia, especially microglia and astrocytes, it is thought that alterations in synaptic function lead to changes in the way that pain is processed within the CNS. It is believed that these changes play a significant part in the development of central sensitisation. There is also evidence that this glial activation may also account for many of the neuro-vegetative features common in persistent pain such as anxiety, depression, fatigue, poor sleep and cognitive problems. It is hoped that medicines that are able to suppress CNS inflammation might help relieve pain, improve function and associated psychiatric symptoms in patients with chronic pain.

Palmitoylethanolamide (PEA) is a naturally occurring fatty acid involved with known anti-inflammatory properties and has been suggested to be involved in the regulation and termination of inflammatory responses within the CNS. It is currently classed as a nutraceutical and available from compounding chemists without prescription. There is some evidence that administration of PEA has analgesic benefits in a variety of causes of persistent pain, although evidence is limited by significant industry support. It does have anecdotal evidence of positive effects and appears to be very well tolerated, with a low risk of serious adverse effects. Given the limitations in current pharmacologic options in the management of persistent pain, it represents a potential useful addition to the current therapeutic options.

The aim of this study is to assess the ability of daily oral administration of PEA to achieve long lasting improvements pain and function in patients being treated in a tertiary hospital pain clinic. Patients will be selected based on evidence of neuro- vegetative features as assessed by the Symptom Severity Score (SSS ) from the 2011 revised ACR Fibromyalgia Criteria regardless of primary pain diagnosis. The study aims to have high external validity. Patients will be randomised to PEA or placebo in addition to their current therapy for a period of 6 months.

Outcomes will be assessed via the electronic Persistent Pain Outcomes Collaborative (ePPOC) questionnaires, with a primary outcome of Pain Interference as assessed by the Brief Pain Inventory (BPI) at 6 months.

Trial website

Trial related presentations / publications

Public notes

Contacts

Principal investigator

Name

Dr Daniel Ellyard

Address

Department of Pain Medicine
Sir Charles Gairdner Hospital
Hospital Ave, Nedlands WA 6009

Country

Australia

Phone

+61 8 6457 3333

Fax

daniel.ellyard@health.wa.gov.au

Contact person for public queries

Name

Daniel Ellyard

Address

Department of Pain Medicine
Sir Charles Gairdner Hospital
Hospital Ave, Nedlands WA 6009

Country

Australia

Phone

+61 8 6457 3333

Fax

daniel.ellyard@health.wa.gov.au

Contact person for scientific queries

Name

Daniel Ellyard

Address

Department of Pain Medicine
Sir Charles Gairdner Hospital
Hospital Ave, Nedlands WA 6009

Country

Australia

Phone

+61 8 6457 3333

Fax

daniel.ellyard@health.wa.gov.au

Data sharing statement

Will individual participant data (IPD) for this trial be available (including data dictionaries)?

Yes

What data in particular will be shared?

Individual scores for each of the primary and secondary outcomes.

When will data be available (start and end dates)?

Following publications of results, no end date

Available to whom?

Journal editors, Researches conducting systemic reviews/meta-analysis

Available for what types of analyses?

systemic reviews/meta-analysis

How or where can data be obtained?

Following written request - de-identified data spread sheets will be supplied

What supporting documents are/will be available?

No Supporting Document Provided

Results publications and other study-related documents

Documents added manually

No documents have been uploaded by study researchers.

Documents added automatically

No additional documents have been identified.

Trial Review

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