Impacted Third Molar ToothNCT06539741
Variability in Analgesic Response to Ibuprofen
An observational study of Impacted Third Molar Tooth and Pain, Acute, run by University of Pennsylvania at 1 site in United States.
Trial summary
Nonsteroidal anti-inflammatory drugs (NSAIDs), like ibuprofen, are recommended as first-line treatment for post-surgical dental pain. However, there is variability in analgesic response, and some patients require supplemental opioids for adequate pain relief. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Impacted Third Molar Tooth, Pain, Acute
- How many people
- 200 participants
- Where
- 1 siteUnited States
- Study dates
- 3 Jan 2025to Sep 2027
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: Patients presenting for surgical extraction of partial or full bony impacted mandibular third molars at the Oral Surgery Clinics at Penn Dental Medicine
Who may be able to join
- Provision of signed and dated informed consent form
- Stated willingness to comply with all study procedures and availability for the duration of the study
- Ability to take oral medication and be willing to adhere to the study treatment regimen
- Men and women greater than 18 years of age requiring extraction of at least one impacted mandibular third molar tooth (at least 50% covered with bone).
- Absence of other major medical problems or contraindications to surgery or study drugs.
- Female subjects of child bearing potential must be using a medically acceptable method of contraception (oral contraception, Depo-Provera injection, IUD, condom with spermicide, diaphragm, cervical cap, progestin implant, abstinence, tubal ligation, oophorectomy, TAH) throughout the entire study period. All female subjects must consent to a urine pregnancy test at screening and a urine pregnancy test on the day of surgery, which must be negative at all time points.
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- Has not ingested caffeine-containing products within 12 hours of surgery.
- All subjects must consent to a urine drug test at screening. Results must be negative (except for THC) unless the subject is on a stable dose of a non-analgesic drug for a legitimate medical purpose. A positive test for THC will be permitted and the frequency of use will be documented. A positive result will be reported to the subject.
- Does not consume more than 1 alcoholic beverage per day on average.
- Subjects must reach a level of at least moderate pain within four hours of surgery completion, with a pain score greater than or equal to 4 on a 0-10 numerical pain scale
- Subjects must be willing and able to complete safety and efficacy diaries.
- An escort must be available to pick up the subject at the end of at the end of the surgical/dosing visit (Visit #2).
Who cannot join
- Female subjects who are pregnant or nursing a child.
- Subjects who have received an investigational drug or used an experimental medical device within 30 days prior to screening, or who gave a blood donation of ≥ one pint within 8 weeks prior to screening.
- Subjects who are sensitive or allergic to ibuprofen, acetaminophen, or their components.
- Subjects who are sensitive or allergic to aspirin or other NSAIDs.
- Subjects who are sensitive or allergic to oxycodone or other opioids (excluding nausea and constipation).
- Presence of a serious medical condition (e.g. poorly controlled hypertension or diabetes, gastrointestinal disorders such as bleeding ulcer, coagulation or bleeding disorders, significantly impaired cardiac, renal, hepatic, respiratory, or thyroid function) that according to the investigator may interfere with interpretation of the study results or compromise the safety of a potential subject.
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- Acute local infection at the time of surgery that could confound post-surgical evaluation.
- Use of any confounding prescription or non-prescription drug within 24 hours of the surgical procedure, including analgesics, sedating antihistamine, sedative, alcohol, or CNS/psychotropic agents (i.e. sleep aids, benzodiazepines). Hormonal contraceptives, hormone replacement therapy (including males taking testosterone as a hormone replacement to treat a documented low testosterone level), or thyroid replacement hormones are allowed. Individuals taking other/additional chronic stable medications can be considered on a case-by-case basis for inclusion in the study if agreed upon by judgment of the investigator.
- Subjects with any abnormal laboratory value or physical finding that according to the investigator may interfere with interpretation of the study results, be indicative of an underlying disease state, or compromise the safety of a potential subject.
- Subjects who have a history of opioid use disorder or other substance use disorder, based upon history and judgment of the Investigator.
- Subjects who are unwilling to provide a blood sample for genetic analyses.
- Employees of the principal investigator, sub-investigators, or relative of an employee who is directly involved in this study.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
University of Pennsylvania School of Dental Medicine
Philadelphia, Pennsylvania, 19104
Stacey Secreto, 215-746-8871, secreto@upenn.edu
Katherine N Theken, PharmD, PhD
About this study
Official title: Mechanisms of Variability in the Analgesic Response to Ibuprofen Following Third Molar Extraction
Nonsteroidal anti-inflammatory drugs (NSAIDs), like ibuprofen, are recommended as first-line treatment for post-surgical dental pain. However, there is variability in analgesic response, and some patients require supplemental opioids for adequate pain relief. The goal of this study is to identify the factors that contribute to the need for opioid after third molar extraction to help limit unnecessary opioid prescriptions in patients who will have good pain relief with ibuprofen alone.
Read the detailed description
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.
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 as 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.
- Conditions
- Impacted Third Molar Tooth, Pain, Acute
- Medical subject headings
- Acute Pain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Complete Responders | Patients who do not require supplemental opioids, in addition to a standard-of-care NSAID-based pain management regimen, for pain relief following third molar extraction | |
| Partial Responders | Patients who require supplemental opioids (oxycodone 5 mg), in addition to a standard-of-care NSAID-based pain management regimen, for pain relief following third molar extraction |
What is being measured
The primary outcome is the main question the study is designed to answer.
Supplemental Opioid Use
Use of oxycodone in addition to ibuprofen + acetaminophen
Measured: Up to 7 days after third molar extraction
Secondary outcomes (7)
Gene Expression Profiling
mRNA levels will be measured in peripheral blood mononuclear cells
Measured: Up to 7 days after third molar extraction
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.
Measured: Up to 7 days after third molar extraction
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.
Measured: Up to 7 days after third molar extraction
DNA sequencing
Assessment of genetic variation
Measured: 1 day
Pain intensity score
Rating of pain from 0 (no pain) to 10 (worst imaginable pain)
Measured: Up to 7 days after third molar extraction
Inflammatory mediator profiling
Assessment of cytokines in plasma
Measured: Up to 7 days after third molar extraction
Complete blood count with differential
Assessment of proportions of red blood cells, white blood cells, and platelets in whole blood
Measured: Up to 7 days after third molar extraction
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Aug 2024
- Study start3 Jan 2025
- Primary completionSep 2027 (estimated)
- Study completionSep 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Impacted Third Molar ToothStudies of the same condition, open and under way.
- More trials run by University of PennsylvaniaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 200 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Pennsylvania
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Dental and Craniofacial Research (NIDCR)
- Responsible party
- Sponsor
- Investigators
- Katherine N Theken, PharmD, PhD, Principal investigator, University of Pennsylvania
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06539741
- Sponsor's protocol ID
- 856367
- Other IDs
- 1R01DE033405-01A1
- Status last verified
- May 2026
- First submitted
- 1 Aug 2024
- Last updated
- 6 May 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Mechanisms of Variability in the Analgesic Response to Ibuprofen Following Third Molar Extraction
- ClinicalTrials.gov ID
- NCT06539741
- Acronym / sponsor ID
- 856367
- Conditions
- Impacted Third Molar Tooth, Pain, Acute
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 200 participants (estimated)
- Lead sponsor
- University of PennsylvaniaUniversity, hospital or other
- Collaborators
- National Institute of Dental and Craniofacial Research (NIDCR)
- Study start
- 3 Jan 2025 (actual)
- Primary completion
- Sep 2027 (estimated)
- Study completion
- Sep 2027 (estimated)
- First posted
- 6 Aug 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Nonsteroidal anti-inflammatory drugs (NSAIDs), like ibuprofen, are recommended as first-line treatment for post-surgical dental pain. However, there is variability in analgesic response, and some patients require supplemental opioids for adequate pain relief. The goal of this study is to identify the factors that contribute to the need for opioid after third molar extraction to help limit unnecessary opioid prescriptions in patients who will have good pain relief with ibuprofen alone.
Detailed description
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.
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 as 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 design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Complete Responders | – | –Patients who do not require supplemental opioids, in addition to a standard-of-care NSAID-based pain management regimen, for pain relief following third molar extraction |
| Partial Responders | – | –Patients who require supplemental opioids (oxycodone 5 mg), in addition to a standard-of-care NSAID-based pain management regimen, for pain relief following third molar extraction |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Patients presenting for surgical extraction of partial or full bony impacted mandibular third molars at the Oral Surgery Clinics at Penn Dental Medicine
Key inclusion criteria (12 listed)
- Provision of signed and dated informed consent form
- Stated willingness to comply with all study procedures and availability for the duration of the study
- Ability to take oral medication and be willing to adhere to the study treatment regimen
- Men and women greater than 18 years of age requiring extraction of at least one impacted mandibular third molar tooth (at least 50% covered with bone).
- Absence of other major medical problems or contraindications to surgery or study drugs.
Key exclusion criteria (12 listed)
- Female subjects who are pregnant or nursing a child.
- Subjects who have received an investigational drug or used an experimental medical device within 30 days prior to screening, or who gave a blood donation of ≥ one pint within 8 weeks prior to screening.
- Subjects who are sensitive or allergic to ibuprofen, acetaminophen, or their components.
- Subjects who are sensitive or allergic to aspirin or other NSAIDs.
- Subjects who are sensitive or allergic to oxycodone or other opioids (excluding nausea and constipation).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Supplemental Opioid Use
Time frame: Up to 7 days after third molar extraction
Use of oxycodone in addition to ibuprofen + acetaminophen
7 secondary outcomes
Gene Expression Profiling
Time frame: Up to 7 days after third molar extraction
COX-1 activity
Time frame: Up to 7 days after third molar extraction
COX-2 activity
Time frame: Up to 7 days after third molar extraction
DNA sequencing
Time frame: 1 day
Pain intensity score
Time frame: Up to 7 days after third molar extraction
Inflammatory mediator profiling
Time frame: Up to 7 days after third molar extraction
Complete blood count with differential
Time frame: Up to 7 days after third molar extraction
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 May 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Katherine N Theken, PharmD, PhD principal investigator
University of Pennsylvania
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Impacted Third Molar Tooth and Pain, Acute, run by University of Pennsylvania at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 6 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Stacey Secreto (215-746-8871, secreto@upenn.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Supplemental Opioid Use (time frame: Up to 7 days after third molar extraction). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 May 2026.