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-a) 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-a 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.

Intervention	Phase
Drug: Thalidomide, Ibuprofen or Diazepam	Phase II

Further Study Details: 

Expected Total Enrollment:  90

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-a) 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-a 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.

Genders Eligible for Study:  Male

Criteria

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 e.g, alcohol, opioids, benzodiazapines

- chronic use of medications confounding assessment of the inflammatory response or analgesia e.g, 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

Please refer to this study by ClinicalTrials.gov identifier  NCT00121563

Maryland
      National Institute of Dental And Craniofacial Research (NIDCR), 9000 Rockville Pike,  Bethesda,  Maryland,  20892,  United States; Recruiting

Study ID Numbers:  050193; 05-D-0193
Record last reviewed:  June 20, 2005
Last Updated:  July 22, 2005
Record first received:  July 20, 2005
ClinicalTrials.gov Identifier:  NCT00121563
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-07-26