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Trial registered on ANZCTR


Registration number
ACTRN12618001637235
Ethics application status
Approved
Date submitted
28/09/2018
Date registered
3/10/2018
Date last updated
3/10/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
The effects of palmitoylethanolamide (PEA) on pain and brain activity.
Scientific title
The effects of a glial inhibitor (palmitoylethanolamide) on brain function and chronic pain intensity in subjects with orofacial neuropathic pain. A pilot study.
Secondary ID [1] 296179 0
None
Universal Trial Number (UTN)
U1111-1221-1296
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Persistent orofacial/ trigeminal neuropathic pain 309806 0
Condition category
Condition code
Neurological 308601 308601 0 0
Studies of the normal brain and nervous system
Neurological 308602 308602 0 0
Other neurological disorders
Other 308603 308603 0 0
Conditions of unknown or disputed aetiology (such as chronic fatigue syndrome/myalgic encephalomyelitis)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Randomized control trial. A total of 60 subjects will be recruited for the study (60 subjects in total comprising 30 subjects in the active treatment and 30 subjects in the placebo group). Participants will be randomly (stratified by age and gender) assigned into either a treatment or placebo group. Treatment group will take 900mg of palmitoylethanolamide (3 x 300mg capsules) orally three times a day with food (morning, noon and night) - total of 2700 mg daily for a total of six weeks. There will be no modifications to the dosage and route of administration during the trial period. To measure patient compliance, at the 6 week follow-up scan, we will ask each subject to return their pill container. Full compliance will result in an empty bottle. At this point we will be able to ascertain whether there are any remaining pills to determine compliance. If there are any pills remaining we will ask the participant if there are reasons why the full complement of pills were not taken.
Intervention code [1] 312507 0
Treatment: Drugs
Comparator / control treatment
The placebo group will take inactive capsules (milk powder) orally three times a day with food for a total of six weeks.
Control group
Placebo

Outcomes
Primary outcome [1] 307568 0
Change in on-going pain intensity indicated on visual analogue scale.
Timepoint [1] 307568 0
3 times a day for 7 weeks post-treatment
Secondary outcome [1] 352304 0
Psychologocal measure of pain catastrophizing using the Pain Catastrophizing Scale (Sullivan et al. 1995)
Timepoint [1] 352304 0
Before treatment and 6 weeks post treatment
Secondary outcome [2] 352305 0
Psychological measure of depression, anxiety and stress using the Depression Anxiety and Stress Scale (DASS) (Lovibond & Lovibond, 1995)
Timepoint [2] 352305 0
Before treatment and 6 weeks post treatment
Secondary outcome [3] 352306 0
Resting state functional magnetic resonance imaging (fMRI): used to explore resting infra-slow brain rhythms
Timepoint [3] 352306 0
Before treatment and 6 weeks post treatment
Secondary outcome [4] 352307 0
Diffusion Tensor Imaging (DTI) scans using MRI: used to explore brain anatomy and in particular astrocyte activation.
Timepoint [4] 352307 0
Before treatment and 6 weeks post treatment
Secondary outcome [5] 352435 0
Arterial spin labelling (ASL) scan using MRI: used to measure resting blood flow as a marker of on-going activity.
Timepoint [5] 352435 0
Before treatment and 6 weeks post treatment
Secondary outcome [6] 352436 0
Substance P measured by collecting 2ml blood via venepuncture.
Timepoint [6] 352436 0
Before treatment and 6 weeks post treatment
Secondary outcome [7] 352437 0
Beta-Endorphin measured by collecting 2ml blood via venepuncture.
Timepoint [7] 352437 0
Before treatment and 6 weeks post treatment
Secondary outcome [8] 352438 0
Brain-derived neurotrophic factor measured by collecting 2ml blood via venepuncture.
Timepoint [8] 352438 0
Before treatment and 6 weeks post treatment

Eligibility
Key inclusion criteria
Subjects with a diagnosis of orofacial / trigeminal neuropathic pain for longer than 3 months duration
Aged over 18 years old
Willingness to give written informed consent, willingness to complete a magnetic resonance imaging study, complete various questionnaires and to have a blood sample taken
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Taking daily analgesic medications such as aspirin, ibuprofen, gabapentin, serotonin reuptake inhibitors, anti-depressants for any conditions within 24 hours of study initiation.
Claustrophobia
Standard MRI exclusion criteria such as the presence of a cardiac pacemaker, artificial heart valve, blood vessel stents, aneurysm clips, cochlear implants, prosthetic devices, magnetically activated implant or device and pregnancy.
History of psychological illness or condition such as to interfere with the patient’s ability to understand the requirements of the study.

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)
The recruitment doctor and the individual processing the data will be unaware of which group each subject is allocated. The assigning individual will not be involved in recruitment process or data processing
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created by computer software
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 0
Type of endpoint(s)
Efficacy
Statistical methods / analysis
Paired t-test for changes in pain intensity scores (significant at p<0.05), pain maps and blood neuropeptide concentrations; ANOVA (with post-hoc comparison) for qualitative psychological assessment questionnaires. For MRI changes, random effects, population based statistical test will be used and will be corrected for multiple comparisons (as per previous analyses by Professor Henderson’s group)

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW

Funding & Sponsors
Funding source category [1] 300769 0
Government body
Name [1] 300769 0
National Health and Medical Research Council
Address [1] 300769 0
National Health and Medical Research Council
GPO Box 1421
Canberra ACT 2601
Country [1] 300769 0
Australia
Primary sponsor type
University
Name
University of Sydney
Address
The University of Sydney
NSW 2006
Australia
Country
Australia
Secondary sponsor category [1] 300335 0
None
Name [1] 300335 0
Address [1] 300335 0
Country [1] 300335 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 301552 0
The University of Sydney Human Research Ethics Committee
Ethics committee address [1] 301552 0
The University of Sydney
NSW 2006
Australia
Ethics committee country [1] 301552 0
Australia
Date submitted for ethics approval [1] 301552 0
05/12/2017
Approval date [1] 301552 0
24/09/2018
Ethics approval number [1] 301552 0
2018/261

Summary
Brief summary
This study entails understanding the effects of palmitoylethanolamide on pain and brain activity. We hope to learn whether palmitoylethanolamide (a natural compound found in certain foods) reduces on-going pain in the face and how this is reflected in changes in brain anatomy and function. Participants will undergo initial screening which involves questionnaires and a 2 ml blood sample, then scanned using an MRI. Participants will then be assigned either the active drug or a placebo for a total of six weeks and asked to rate their pain daily for the entire period. After six weeks, participants will redo the questionnaires, provide another 2 ml of blood and be scanned using an MRI. We believe that after six weeks of treatment, patients will experience a decrease in pain intensity and MRI scans will show changes in anatomy and function that reflect the decreases in pain.
Trial website
Trial related presentations / publications
Public notes
Attachments [1] 3116 3116 0 0

Contacts
Principal investigator
Name 87358 0
Prof Luke Henderson
Address 87358 0
Room S518
Anderson Stuart Building, F13
The University of Sydney
NSW 2006 AUSTRALIA
Country 87358 0
Australia
Phone 87358 0
+61 293517063
Fax 87358 0
Email 87358 0
luke.henderson@sydney.edu.au
Contact person for public queries
Name 87359 0
Prof Luke Henderson
Address 87359 0
Room S518
Anderson Stuart Building, F13
The University of Sydney
NSW 2006 AUSTRALIA
Country 87359 0
Australia
Phone 87359 0
+61 293517063
Fax 87359 0
Email 87359 0
luke.henderson@sydney.edu.au
Contact person for scientific queries
Name 87360 0
Prof Luke Henderson
Address 87360 0
Room S518
Anderson Stuart Building, F13
The University of Sydney
NSW 2006 AUSTRALIA
Country 87360 0
Australia
Phone 87360 0
+61 293517063
Fax 87360 0
Email 87360 0
luke.henderson@sydney.edu.au

No data has been provided for results reporting
Summary results
Not applicable