Clinical Trial Details
— Status: Active, not recruiting
Administrative data
| NCT number |
NCT05406726 |
| Other study ID # |
HP-00101407 |
| Secondary ID |
|
| Status |
Active, not recruiting |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
March 22, 2023 |
| Est. completion date |
September 2024 |
Study information
| Verified date |
April 2024 |
| Source |
University of Maryland, Baltimore |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
The purposes of this 1-year proof of feasibility and acceptability pilot study are twofold.
First to determine if participants with knee osteoarthritis (KOA) will comply with taking
palmitoylethanolamide (PEA) dietary supplement for 6 weeks and adhere to taking it as
directed. Second is to gain preliminary data to elucidate mechanisms (protein signatures,
inflammatory markers and neurobiological signaling pathways) by which PEA, a lipid-based
endocannabinoid, works to alter pain sensitivity in adults with KOA. In the simplest terms
possible, we need to provide evidence that PEA changes the protein signature in order to
provide evidence to establish mechanism.
Description:
Knee osteoarthritis (KOA) affects nearly 30% of adults aged 60 years or older and causes
significant pain and disability.1 Neurophysiological testing (quantitative sensory testing
(QST)) demonstrates that KOA pain has both peripheral and central mechanisms, which vary by
individual.2 Adults with central KOA pain tend to be resistant to traditional pain treatment
and have substantial pain even after knee replacement surgery.3 There is a growing body of
evidence to support the scientific premise that endocannabinoids and related molecules, in
particular PEA, can improve KOA pain through anti-inflammatory and analgesic pathways.4,5 PEA
has little or no known side effects and is safe for human consumption.6 However, there is
little known regarding the specific mechanisms by which PEA works to relieve KOA pain or for
whom it might work best. We will begin to address this mechanistic question in this pilot
study, which will provide data regarding therapeutic strategies within the endocannabinoid
system to reduce KOA pain. The National Academies of Science, Engineering and Medicine report
on the Health Effects of Cannabis and Cannabinoids (2017), supports cannabinoids as treatment
for chronic pain, but highlighted the need for quality clinical trials. To fill this gap, the
purpose of this study is to explore the impact of oral PEA, a non-psychoactive
endocannabinoid enhancer with little to no side effects, to alter pain related biomarkers.
Our central hypothesis is that PEA will alter pain related protein signatures, inflammatory
markers, and neurophysiological changes in adults with KOA pain.
The investigators propose a crossover clinical trial of 20 adults with self-reported medical
diagnosis of KOA and knee pain (min 4/10 on numeric rating scale). This study will explore
mechanisms of taking 1200mg of oral PEA daily for seven days (loading dose) then 600 mg daily
for an additional 5 weeks (six weeks total). Ten participants will take PEA for 6 weeks while
the other ten will receive placebo. Then the groups will switch, with the first group
receiving placebo and the second group receiving PEA. PEA takes 4 to 6 weeks to reduce KOA
pain. 4,5 Participants will have blood drawn and quantitative sensory testing at baseline, 6-
and 12-weeks follow-up. Participants will be asked to bring in their PEA/placebo bottles for
pill counts to track adherence and will be asked about side effects at each study visit.
The investigators will test the central hypothesis and attain the objectives via the
following specific aims:
Specific Aim 1: To examine the impact of oral PEA placebo on the protein signature of adults
with KOA pain. We will use high-resolution liquid chromatography-tandem mass spectrometry to
examine the entire proteome of the platelet rich plasma (isolated from whole blood) from each
participant/time point to explore whether the PEA can alter the signaling pathways ascribed
to KOA pain. We hypothesize that PEA will reduce the pro-inflammatory signaling pathways in
the systemic proteome among participants in the PEA groups as compared to placebo.
Specific Aim 2: To elucidate the effects of oral PEA vs. placebo on systemic inflammatory
markers related to KOA pain. We will measure key inflammatory markers in KOA including
interleukin (IL)-6, IL-1β, IL-8, IL-10, IL-15, c-reactive protein (CRP) and tumor necrosis
factor-α at each study visit. We hypothesize that PEA will reduce the expression of
inflammatory markers seen after walking in KOA participants as compared to placebo.
Specific Aim 3: To determine the alterations in neurophysiological changes as measured by
Quantitative Sensory Testing (QST) among participants taking PEA vs. placebo. For QST, we
will measure the pressure pain detection and threshold, heat and cold detection and
threshold, and mechanical temporal summation at the affected knee and contralateral forearm
at each study visit. We hypothesize that PEA will alter central and peripheral pain pathways
among adults with KOA. We will also compare the biologic pain pathways to the proteome and
inflammatory markers.
