Etanercept (Enbrel) to Treat Pain and Swelling After Third Molar Extraction
Information source: National Institutes of Health Clinical Center (CC)
Information obtained from ClinicalTrials.gov on June 20, 2008
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Healthy; Inflammation
Intervention: etanercept (Enbrel) (Drug)
Phase: Phase 2
Sponsored by: National Institute of Dental and Craniofacial Research (NIDCR)
This study will evaluate the effects of the anti-inflammatory drug etanercept (Enbrel) on
relieving pain and swelling after oral surgery. The Food and Drug Administration has
approved Enbrel for treating symptoms of rheumatoid arthritis, including pain.
Healthy volunteers 16 to 35 years of age who require third molar (wisdom teeth) extractions
may be eligible for this study. Participants must not be allergic to aspirin or to
non-steroidal anti-inflammatory drugs (NSAIDs). Candidates will be screened for eligibility
with a medical history and oral examination, including X-rays if needed.
Participation in the study requires four clinic visits: two for surgery and two for
Patients will have ultrasound pictures taken to measure cheek size. One hour before surgery,
they will receive a dose of either 25 milligrams (mg) of Enbrel; 15 mg of the standard pain
medicine Toradol; or a placebo (salt-water) through an arm vein. A local injection of an
anesthetic (lidocaine) will be given before surgery to numb the mouth, and a sedative
(Versed) will be infused through a vein to induce sleepiness. When the anesthetic takes
effect, a small piece of tissue will be removed from the inside of the cheek, and then the
upper and lower molars on one side of the mouth will be extracted. After surgery, a small
piece of tubing will be placed in the lower extraction site, from which samples will be
collected to measure chemicals involved in pain and inflammation. Patients will stay in the
clinic for 4 hours after surgery while the anesthetic wears off and will complete pain
questionnaires during that time. If, an hour after surgery, patients have pain that is not
relieved by the treatment given before surgery, they may receive acetaminophen (Tylenol) and
codeine for pain. Another biopsy will be taken (under local anesthetic) from the inside of
the cheek when pain occurs or at the end of the 4-hour observation period. The tubing then
will be removed and the patient discharged with Tylenol and codeine for pain.
Patients will return to the clinic in the morning 48 hours after the oral surgery for a 1- to
2-hour visit. They will fill out questionnaires, undergo ultrasound imaging of both cheeks
and have another biopsy taken from the inside of the cheek on the operated side.
Visits 3 and 4:
Three weeks after the first surgery patients will schedule extraction of the two wisdom teeth
on the other side of the mouth, and the procedures for visits 1 and 2 will be repeated.
Official title: Safety and Efficacy of a TNF Receptor Fusion Protein for Injury-Induced Inflammation and Sequelae
Study design: Treatment, Safety/Efficacy Study
The proposed investigation is a randomized, double-blind, placebo and positive-controlled
within-subjects design clinical study to evaluate the role of the cytokine tumor necrosis
factor (TNF) in acute inflammation using a specific TNF receptor antagonist, etanercept
(Enbrel, Immunex Corporation, Seattle, WA). The goal of this study is to determine whether
inhibition of TNF bioactivity can attenuate acute inflammation. The anti-inflammatory and
adverse effects of etanercept, a recombinant TNF receptor fusion protein, will be evaluated
using a model of tissue injury, the oral surgery model. Briefly, healthy volunteers referred
for third molar extraction will undergo the surgical extraction of third molars with local
anesthesia and conscious sedation. At the completion of the surgical procedure, a
microdialysis probe will be placed under the mucogingival flap previously elevated for the
surgical procedure and subjects will be observed for pain and swelling over the course of
four hours following surgery. Tissue biopsies prior to and following surgery will be
obtained from the buccal mucosa. Etanercept or control will be administered parenterally one
hour prior to surgery. Tissue levels of pro-inflammatory cytokines, growth factors, and
inflammatory mediators will be measured at time intervals postoperatively. Pain and swelling
will be assessed postoperatively over the course of four hours and at 48 hours.
Demonstration of amelioration of pain, swelling, and/or changes in levels of tissue mediators
will be taken as evidence of an acute anti-inflammatory effect of etanercept. Since the
fusion protein (hereafter, TNFR: fc) specifically binds TNF-alpha and prevents its interaction
with cellular receptors, changes in the inflammatory cascade and clinical endpoints of
inflammation may provide insight into role of TNF-alpha in the pathophysiology of acute
inflammation and its clinical sequela.
Minimum age: N/A.
Maximum age: N/A.
Male or female volunteers referred for extraction of third molars willing to undergo two
surgical appointments for the extraction of unilateral third molars.
Between the ages of 16 to 35 years (based upon eruption patterns and age-related
complications associated with surgical extraction of third molars).
In good general health - ASA status 1 or 2 (healthy subjects based upon criteria for safe
outpatient conscious sedation).
Willing to undergo observation period for four hours postoperatively.
Willing to return at 48 hours for measurement of pain, swelling, and tissue biopsy.
Willing to return for a total of four visits beyond the screening visit.
Pregnant or lactating females.
Current mental disorder or substance abuse.
Allergy to aspirin or NSAIDs.
Chronic use of medications confounding assessment of the inflammatory response or analgesia
(antihistamines, NSAIDs, steroids, antidepressants).
Presence of chronic debilitating disease (such as diabetes, rheumatoid arthritis, liver
Presence of symptomatic tooth suggesting infection or inflammation.
Unusual surgical difficulty encountered during the surgical procedure.
Locations and Contacts
National Institute of Dental And Craniofacial Research (NIDCR), Bethesda, Maryland 20892, United States
Mohler KM, Torrance DS, Smith CA, Goodwin RG, Stremler KE, Fung VP, Madani H, Widmer MB. Soluble tumor necrosis factor (TNF) receptors are effective therapeutic agents in lethal endotoxemia and function simultaneously as both TNF carriers and TNF antagonists. J Immunol. 1993 Aug 1;151(3):1548-61.
Fisher CJ Jr, Agosti JM, Opal SM, Lowry SF, Balk RA, Sadoff JC, Abraham E, Schein RM, Benjamin E. Treatment of septic shock with the tumor necrosis factor receptor:Fc fusion protein. The Soluble TNF Receptor Sepsis Study Group. N Engl J Med. 1996 Jun 27;334(26):1697-702.
Chen L, Salafranca MN, Mehta JL. Cyclooxygenase inhibition decreases nitric oxide synthase activity in human platelets. Am J Physiol. 1997 Oct;273(4 Pt 2):H1854-9.
Starting date: July 2000
Ending date: May 2004
Last updated: March 3, 2008