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Etanercept (Enbrel) to Treat Pain and Swelling After Third Molar Extraction

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ClinicalTrials.gov Identifier: NCT00006070
Recruitment Status : Completed
First Posted : July 19, 2000
Last Update Posted : March 4, 2008
Information provided by:
National Institutes of Health Clinical Center (CC)

Brief Summary:

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 follow-up:

Visit 1:

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.

Visit 2:

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.

Condition or disease Intervention/treatment Phase
Healthy Inflammation Drug: etanercept (Enbrel) Phase 2

Detailed Description:
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.

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Study Type : Interventional  (Clinical Trial)
Enrollment : 86 participants
Primary Purpose: Treatment
Official Title: Safety and Efficacy of a TNF Receptor Fusion Protein for Injury-Induced Inflammation and Sequelae
Study Start Date : July 2000
Study Completion Date : May 2004

Resource links provided by the National Library of Medicine

Drug Information available for: Etanercept

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


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 disease, etc).

Presence of symptomatic tooth suggesting infection or inflammation.

Unusual surgical difficulty encountered during the surgical procedure.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00006070

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United States, Maryland
National Institute of Dental And Craniofacial Research (NIDCR)
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
National Institute of Dental and Craniofacial Research (NIDCR)
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ClinicalTrials.gov Identifier: NCT00006070    
Other Study ID Numbers: 000168
First Posted: July 19, 2000    Key Record Dates
Last Update Posted: March 4, 2008
Last Verified: May 2004
Keywords provided by National Institutes of Health Clinical Center (CC):
Oral Surgery
Additional relevant MeSH terms:
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Pathologic Processes
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Antirheumatic Agents
Gastrointestinal Agents
Immunosuppressive Agents
Immunologic Factors