Prostanoid Levels After Medication to Prevent Pain Following Third Molar (Wisdom Tooth) Extraction

NCT00078104 | Completed Phase 2

• 2 other identifiers: 04012404-D-0124
• Study Type: interventional
• Target: 148
• Locations: 1 country
• Sites: 1

Brief Summary

This study will evaluate how well different medications work to relieve pain following third molar (wisdom tooth) extraction. Scientists believe that hormone-like substances called prostanoids contribute to pain following oral surgery. Prostanoids are produced by cyclooxygenase (COX) enzymes. This study will examine how different medicines inhibit the COX enzymes and reduce the amount of prostanoids, and thus the amount of inflammation and pain. The study will also look at genetic factors involved in the production of prostanoids and the response to pain medication. (Only the bottom two wisdom teeth are extracted for this study. Patients whose top wisdom teeth also need to be removed will have those teeth extracted, also free of charge, at least 2 weeks after the first surgery.) Healthy normal volunteers between 16 and 35 years of age who are in general good health and who require third molar extraction may be eligible for this study. Candidates are screened with a medical history and oral examination, including dental x-rays as needed to confirm the need for third molar removal. On the morning of surgery, patients have blood drawn to obtain DNA for genetic study. Women of childbearing age have a urine pregnancy test. One hour before surgery, patients receive a dose of rofecoxib (Vioxx® (Registered Trademark)), acetaminophen (Tylenol® (Registered Trademark)), or placebo (a pill with no active ingredient). A half-hour before surgery, they receive either a standard painkiller called keterolac (Toradol® (Registered Trademark))) or placebo through an arm vein. All patients also receive the sedative midazolam (Versed® (Registered Trademark)), also through an arm vein, to induce drowsiness and a local anesthetic (lidocaine) to numb the mouth. After the mouth is numbed, but before the wisdom teeth are extracted, a biopsy (removal of a small piece of tissue) is conducted in the area of the cheek next to the wisdom tooth. After the surgery, a small piece of tubing is placed into both extraction sites. Every 20 minutes for the next 3 hours, inflammatory fluid is collected from the tubing to measure chemicals that are believed to cause pain and swelling. Patients complete questionnaires every 20 minutes to rate their pain. Those who still have pain an hour after surgery may request and receive a "rescue drug" called tramadol (Ultram® (Registered Trademark)) for pain relief. Patients remain in the clinic from 3 to 6 hours to monitor the effects of the study drugs as the anesthetic wears off. After surgery a second biopsy is done to measure any changes in the chemicals being produced in response to the surgery. For this biopsy, patients are assigned to one of two groups - one group has the second biopsy within 3 hours of surgery, before taking the rescue drug, and the other group returns to the clinic the next morning for a biopsy 24 hours after surgery. Patients in the second group leave the clinic after surgery with two pain medications (tramadol and the study drug) and forms to record pain ratings at home. They are permitted to take only the pain medications provided and only at certain times. At the end of their participation in the study, all patients are given the pain medication flurbiprofen (Ocufen® (Registered Trademark)) to take at home.

Conditions

Healthy; Tooth Extraction

Keywords

Prostanoid; Cyclooxygenase (COX); Selective Cox Inhibitor; Acute Peripheral Inflammation; Neuronal Expression of COX; Pain; Coxibs; Wisdom Teeth; Third Molar Extraction; Third Molar Impaction

Interventions

Extraction of wisdom teeth PROCEDURE

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female volunteers referred for third molar extraction willing to undergo 2 or 3 visits: 1 screening visit; 1 surgical appointment; and possible 1 follow-up research-related appointment
• Between the ages of 16 to 35 years (based upon eruption patterns and age-related complications associated with surgical extraction of third molars)
• In general good health- American Society of Anesthesiologists (ASA) status I or II (healthy subjects based upon criteria for safe administration of out-patient conscious sedation)
• Willing to undergo observation period for three hours postoperatively
• Ability to complete a 100 mm visual analog scale and a category scale every 20 minutes for the first 3 postoperative hours
• Willing to have a microdialysis probe placed beneath the surgical flap during the first 3 hours post-surgery
• Willing to have a preoperative biopsy on the day of surgery, and a postoperative biopsy either within 3 hours or at 24 hours following surgery
• Willing to return, if needed, 24 hours post-operation for the postoperative biopsy
• Must have two lower partial bony impacted wisdom teeth fully covered by intact soft tissue (rating equals 3) or fully bony impacted (rating equals 4) wisdom teeth (mandibular third molars)
• As assessed at the screening visit, the sum of the mandibular third molar surgical difficulty ratings must be between 6 to 8 in order to evaluate subjects experiencing similar pain levels

You may not qualify if:

• Patients who are allergic to aspirin, NSAIDs, sulfites, or amide anesthetics
• Patients who have had asthma, or hives
• Patients who are pregnant or nursing
• Patients with history of peptic ulcers and/or GI bleeding
• Chronic use of medications confounding the assessment of the inflammatory response or analgesia, for example, NSAIDs, COX-2 inhibitors, antihistamines, steroids, antidepressants
• Patients who have significant psychiatric history
• Patients who have a clinical signs suggestive of infection, inflammation, or pre-existing pain at either extraction site
• Patients with severe kidney disease
• Patients who are taking any of the following drugs: ACE inhibitor; potassium sparing diuretics; aspirin on a near daily basis; coumadin or other blood thinners
• Patients who are taking drugs known to inhibit P450 2C9 and drugs metabolized by P450 2D6
• Patients who have G6PD deficiency and those taking St. John's Wort
• Unusual surgical difficulty (determined from panoramic radiograph or during the actual surgery)

Sponsors & Collaborators

• National Institute of Dental and Craniofacial Research (NIDCR): lead

Study Sites (1)

National Institute of Dental And Craniofacial Research (NIDCR)

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Bazan NG. COX-2 as a multifunctional neuronal modulator. Nat Med. 2001 Apr;7(4):414-5. doi: 10.1038/86477. No abstract available.

  PMID: 11283664 BACKGROUND

• Butte A. The use and analysis of microarray data. Nat Rev Drug Discov. 2002 Dec;1(12):951-60. doi: 10.1038/nrd961.

  PMID: 12461517 BACKGROUND

• Chandrasekharan NV, Dai H, Roos KL, Evanson NK, Tomsik J, Elton TS, Simmons DL. COX-3, a cyclooxygenase-1 variant inhibited by acetaminophen and other analgesic/antipyretic drugs: cloning, structure, and expression. Proc Natl Acad Sci U S A. 2002 Oct 15;99(21):13926-31. doi: 10.1073/pnas.162468699. Epub 2002 Sep 19.

  PMID: 12242329 BACKGROUND

MeSH Terms

Conditions

Pain

Condition Hierarchy (Ancestors)

Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: phase 2
• Purpose: TREATMENT
• Sponsor Type: NIH

Study Record Dates

• First Submitted: February 18, 2004
• First Posted: February 19, 2004
• Study Start: February 1, 2004
• Study Completion: October 1, 2005
• Last Updated: March 4, 2008

Record last verified: 2005-10

Locations

US (1)