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

Phase 2
Not Enrolling

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Trial Information

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

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.

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


- 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

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Primary Purpose: Treatment


United States: Federal Government

Study ID:




Start Date:

July 2005

Completion Date:

February 2006

Related Keywords:

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



National Institute of Nursing Research (NINR) Bethesda, Maryland  20892