This research study will evaluate inter-individual variability in the analgesic response to the non-steroidal anti-inflammatory drug (NSAID) ibuprofen after third molar extraction surgery. It will also investigate demographic, clinical, genetic, and environmental factors that cause this variability.
The dramatic increase in opioid prescriptions over the past years has been linked to the concomitant rise in opioid addiction and to deaths from opioid abuse. Young adults' initial exposure to opioid analgesics is often following extraction of their impacted third molars, with an average of 5,000,000 cases in the USA per year. Over-prescribing of opioids for surgical pain, often 2-5 times more than patients actually use, further exacerbates this problem, as patients tend to save leftover pills rather than discard them. Up to 70% of individuals who become addicted to prescription opioids had access to leftover pills prescribed for others. This is particularly troubling as the odds of transitioning to heroin from prescription opioid abuse are much higher than other suspected gateway drugs, about 40 fold greater than non-gateway drug users. Heroin is now often laced with fentanyl derivatives making overdose and death more likely in even the most opioid tolerant individuals. Multiple studies have demonstrated that non-addicting nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen and diclofenac are effective in relieving pain after dental impaction surgery, being at least equally efficacious to optimal doses of immediate release opioid formulations combined with acetaminophen. However, these assessments of pain relief represent average scores and approximately 22% and 50% of individuals required additional opioid-containing rescue analgesics when ibuprofen and diclofenac were employed at FDA-approved dosages. A deeper understanding of the sources of variability in pain relief should allow improvements in the overall efficacy of NSAIDs by targeting treatment to those who are most likely to receive sufficient pain relief. Thus, optimizing pain therapy with NSAIDs by personalization would be expected to help limit the unnecessary prescription of highly addicting immediate release opioids. Moreover, these results may have applicability to other types of pain that are driven by inflammation.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
OTHER
Masking
QUADRUPLE
Enrollment
86
400 mg by mouth every 4 hours for 2 days after third molar extraction and then as needed for pain up to 7 days after third molar extraction
500 mg by mouth every 4 hours for 2 days after third molar extraction and then as needed for pain up to 7 days after third molar extraction
By mouth
Institute for Translational Medicine and Therapeutics (ITMAT), University of Pennsylvania School of Medicine
Philadelphia, Pennsylvania, United States
Analgesic response
Use of opioid rescue medication
Time frame: Up to 7 days after third molar extraction
Ibuprofen plasma concentrations
Assessed by measuring the amount of ibuprofen in plasma
Time frame: Up to 7 days
Acetaminophen plasma concentrations
Assessed by measuring the amount of acetaminophen in plasma
Time frame: Up to 7 days
Gene expression profiling
mRNA levels will be measured in peripheral blood mononuclear cells
Time frame: Up to 7 days
COX-1 activity
COX-1 activity will be measured ex vivo using a whole blood assay and in vivo by quantifying concentrations of prostaglandin metabolites in urine.
Time frame: Up to 7 days
COX-2 activity
COX-2 activity will be measured ex vivo using a whole blood assay and in vivo by quantifying concentrations of prostaglandin metabolites in urine.
Time frame: Up to 7 days
DNA sequencing
Assessment of genetic variation
Time frame: 1 day
Urinary metabolomics
Assessed by measuring levels of metabolites in urine
Time frame: Up to 7 days
Plasma metabolomics
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5 mg by mouth every 6 hours as needed for pain
Assessed by measuring levels of metabolites in plasma
Time frame: Up to 7 days
Composition of the gut microbiome
Assessed by evaluating the microbes present in a stool sample
Time frame: 1 day
Composition of the oral microbiome
Assessed by evaluating the microbes present in an oral swab
Time frame: 1 day
Pain intensity score
Rating of pain from 0 (no pain) to 10 (worst imaginable pain)
Time frame: Up to 7 days
Inflammatory mediator profiling
Assessment of cytokines in plasma
Time frame: Up to 7 days
C-reactive protein
Assessment C-reactive protein in serum
Time frame: Up to 7 days
Procalcitonin levels
Assessment of procalcitonin in serum
Time frame: Up to 7 days
Complete blood count with differential
Assessment of proportions of red blood cells, white blood cells, and platelets in whole blood
Time frame: Up to 7 days