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

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.

Timeline

Start

2005-07

Primary completion

—

Completion

2006-02

Publications

• Background Anthonsen MW, Solhaug A, Johansen B. Functional coupling between secretory and cytosolic phospholipase A2 modulates tumor necrosis factor-alpha- and interleukin-1beta-induced NF-kappa B activation. J Biol Chem. 2001 Aug 10;276(32):30527-36. doi: 10.1074/jbc.M008481200. Epub 2001 Jun 4.
• Background Barosi G, Grossi A, Comotti B, Musto P, Gamba G, Marchetti M. Safety and efficacy of thalidomide in patients with myelofibrosis with myeloid metaplasia. Br J Haematol. 2001 Jul;114(1):78-83. doi: 10.1046/j.1365-2141.2001.02918.x.
• Background Bastuji-Garin S, Ochonisky S, Bouche P, Gherardi RK, Duguet C, Djerradine Z, Poli F, Revuz J; Thalidomide Neuropathy Study Group. Incidence and risk factors for thalidomide neuropathy: a prospective study of 135 dermatologic patients. J Invest Dermatol. 2002 Nov;119(5):1020-6. doi: 10.1046/j.1523-1747.2002.19502.x.

Drugs

Indications

No indication recorded.