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

NCT00121563 | Completed Phase 2

• 2 other identifiers: 05019305-NR-0193
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 1

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.

Conditions

Pain

Keywords

Cytokines; Inflammation; Pain; Injury; Peripheral; Wisdom Teeth; Third Molar Extraction

Interventions

Thalidomide, Ibuprofen or Diazepam DRUG

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• National Institute of Nursing Research (NINR): lead

Study Sites (1)

National Institute of Nursing Research (NINR)

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• 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.

  PMID: 11390371 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.

  PMID: 11472348 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.

  PMID: 12445187 BACKGROUND

MeSH Terms

Conditions

Pain; Inflammation; Wounds and Injuries

Interventions

Thalidomide; Ibuprofen; Diazepam

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Phenylpropionates; Benzodiazepinones; Benzodiazepines; Benzazepines

Study Design

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

Study Record Dates

• First Submitted: July 20, 2005
• First Posted: July 21, 2005
• Study Start: July 1, 2005
• Study Completion: February 1, 2006
• Last Updated: March 4, 2008

Record last verified: 2006-02

Locations

US (1)