Evaluation of a TNF-Alpha Modulator for Clinical and Molecular Indicators of Analgesic Effect

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00121563
Recruitment Status : Completed
First Posted : July 21, 2005
Last Update Posted : March 4, 2008
Information provided by:
National Institutes of Health Clinical Center (CC)

Brief Summary:

This study will evaluate the role of thalidomide, a tumor necrosis factor (TNF)-alpha modulator, on severe inflammation and relief of pain following extraction of wisdom teeth. TNFs are substances that affect the pathways of pain. This study involves an experimental group in which patients will be given thalidomide or a placebo (an inactive substance); a negative control group receiving the medication diazepam or a placebo; and a positive control group receiving diazepam or ibuprofen.

Patients who are males ages 16 to 35, who are not allergic to aspirin or other nonsteroidal anti-inflammatory drugs (known as NSAIDs), sulfites, or certain anesthetics, and who in good health may be eligible for this study. Females are not eligible, owing to the risks that thalidomide presents to unborn children. To minimize the risk of fetal malformations, male patients who participate must use a condom during sexual intercourse for 4 weeks following the study and must not donate blood for 4 weeks.

The medications used in the study will be given 1 hour before surgery. Then after the wisdom teeth are removed, a small piece of tubing will be placed into both sides of the patient's mouth where the teeth were removed. Every 20 minutes, for the next 6 hours, the researchers will collect inflammatory fluid from the tubing, to measure for changes in anti-inflammatory action. If they request pain relievers, patients will receive the medication ketorolac (Toradol), used for short-term treatment of moderately severe acute pain. Side effects of thalidomide include fatigue, dizziness, and rash. The use of ibuprofen and ketorolac may include the risk of gastrointestinal ulcers and bleeding. Diazepam can cause involuntary muscle movements and drowsiness, as well as dizziness lasting for up to 24 hours after it has been used as sedation. Patients will be instructed not to try to walk alone or to try to drive a vehicle during that period. Other risks related to participation in this study include those usually experienced with removal of wisdom teeth-that is, pain and swelling, bruising from insertion of the sedative into a vein (if needed), possible infection at the extraction site, prolonged bleeding, and numbness.

Benefits from participating are having wisdom teeth removed at no cost as well as close monitoring before and after surgery. Results from the study may help people in the future by improving the management of pain following surgery.

Condition or disease Intervention/treatment Phase
Pain Drug: Thalidomide, Ibuprofen or Diazepam Phase 2

Detailed Description:
The proposed investigation is a randomized, double-blind, placebo and positive-controlled clinical study to evaluate the role of the cytokine tumor necrosis factor alpha (TNF-alpha) modulator, thalidomide, in acute inflammation and analgesia. The analgesic effect of thalidomide, a putative TNF-alpha modulator, will be evaluated using a model of tissue injury, the oral surgery model. Briefly, healthy males referred for third molar extraction will undergo the surgical extraction of third molars using standard surgical methods. 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 over the course of six hours following surgery. Thalidomide or control will be administered one hour prior to surgery. Tissue levels of pro-inflammatory cytokines, and inflammatory mediators will be measured at time intervals postoperatively concomitant with pain measurements. Pain will be assessed postoperatively over the course of six hours. Demonstration of amelioration of pain is the primary outcome measure; changes in levels of tissue mediators will be taken as evidence of an acute anti-inflammatory effect of thalidomide. Based on our previous work with the fusion protein etanercept (TNFR:fc) which specifically binds TNF-alpha and prevents its interaction with cellular receptors, similar changes in the inflammatory cascade and clinical endpoints of inflammation may provide insight into the activity of thalidomide on acute inflammation and its clinical sequela, pain.

Study Type : Interventional  (Clinical Trial)
Enrollment : 90 participants
Primary Purpose: Treatment
Official Title: Evaluation of TNF-Alpha Modulator for Clinical and Molecular Indicators of Analgesic Effect
Study Start Date : July 2005
Study Completion Date : February 2006

Resource links provided by the National Library of Medicine

Drug Information available for: Diazepam

Information from the National Library of Medicine

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


  • male patients referred for extraction of third molars willing to undergo surgical extraction of all indicated third molars
  • a minimum of one partial-bony impacted third molar, with a total difficulty score total of not less than 8
  • 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 six hours postoperatively


  • females
  • current mental disorder or substance abuse
  • allergy to aspirin, NSAIDs, or sulfonamide
  • history of peptic ulcers and GI bleeding
  • concurrent use of agents which may potentiate the sedative effect of study drugs, alcohol, opioids, benzodiazapines
  • 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
  • excessive surgical difficulty encountered during the surgical procedure, resulting in a difficulty score of 5 for any tooth
  • patients with acute narrow angle glaucoma, and open angle glaucoma who are not receiving therapy

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 identifier (NCT number): NCT00121563

United States, Maryland
National Institute of Nursing Research (NINR)
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
National Institute of Nursing Research (NINR)

Publications: Identifier: NCT00121563     History of Changes
Other Study ID Numbers: 050193
First Posted: July 21, 2005    Key Record Dates
Last Update Posted: March 4, 2008
Last Verified: February 2006

Keywords provided by National Institutes of Health Clinical Center (CC):
Wisdom Teeth
Third Molar Extraction

Additional relevant MeSH terms:
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Antirheumatic Agents
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Leprostatic Agents
Anti-Bacterial Agents
Anti-Infective Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors
Antineoplastic Agents
Adjuvants, Anesthesia
Autonomic Agents
Gastrointestinal Agents
Hypnotics and Sedatives