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

Primary Purpose

Healthy, Inflammation

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
etanercept (Enbrel)
Sponsored by
National Institute of Dental and Craniofacial Research (NIDCR)
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for Healthy focused on measuring Oral Surgery, Swelling, Pain, TNF, Etanercept

Eligibility Criteria

undefined - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

INCLUSION CRITERIA 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. EXCLUSION CRITERIA 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.

Sites / Locations

  • National Institute of Dental And Craniofacial Research (NIDCR)

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

First Posted
July 18, 2000
Last Updated
March 3, 2008
Sponsor
National Institute of Dental and Craniofacial Research (NIDCR)
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1. Study Identification

Unique Protocol Identification Number
NCT00006070
Brief Title
Etanercept (Enbrel) to Treat Pain and Swelling After Third Molar Extraction
Official Title
Safety and Efficacy of a TNF Receptor Fusion Protein for Injury-Induced Inflammation and Sequelae
Study Type
Interventional

2. Study Status

Record Verification Date
May 2004
Overall Recruitment Status
Completed
Study Start Date
July 2000 (undefined)
Primary Completion Date
undefined (undefined)
Study Completion Date
May 2004 (undefined)

3. Sponsor/Collaborators

Name of the Sponsor
National Institute of Dental and Craniofacial Research (NIDCR)

4. Oversight

5. Study Description

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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Healthy, Inflammation
Keywords
Oral Surgery, Swelling, Pain, TNF, Etanercept

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Enrollment
86 (false)

8. Arms, Groups, and Interventions

Intervention Type
Drug
Intervention Name(s)
etanercept (Enbrel)

10. Eligibility

Sex
All
Accepts Healthy Volunteers
No
Eligibility Criteria
INCLUSION CRITERIA 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. EXCLUSION CRITERIA 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.
Facility Information:
Facility Name
National Institute of Dental And Craniofacial Research (NIDCR)
City
Bethesda
State/Province
Maryland
ZIP/Postal Code
20892
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
8393046
Citation
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.
Results Reference
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PubMed Identifier
8637514
Citation
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. doi: 10.1056/NEJM199606273342603.
Results Reference
background
PubMed Identifier
9362253
Citation
Chen L, Salafranca MN, Mehta JL. Cyclooxygenase inhibition decreases nitric oxide synthase activity in human platelets. Am J Physiol. 1997 Oct;273(4):H1854-9. doi: 10.1152/ajpheart.1997.273.4.H1854.
Results Reference
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Etanercept (Enbrel) to Treat Pain and Swelling After Third Molar Extraction

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