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

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.

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Key information

Conditions

Pain Inflammation Neurologic Manifestations Pathologic Processes Pathological Conditions, Signs and Symptoms Signs and Symptoms Wounds and Injuries

Sex eligibility

Male

Study type

Interventional

Phase

Phase 2

Primary location

National Institute of Nursing Research (NINR)

Bethesda, Maryland, 20892, United States

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

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

Exclusion criteria

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

Treatment and study plan

Thalidomide, Ibuprofen or Diazepam

Drug

Sponsors and collaborators

Lead sponsor

National Institute of Nursing Research (NINR)

Nih

Registry information

Official study title

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

Important dates

Study start: 2005
Study completion: 2006
First posted: Jul 21, 2005
Registry last updated: Mar 4, 2008

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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