Genetic Basis For Variation In NSAID Analgesia In A Clinical Model Of Acute Pain
Condition: Pain
MeSH terms: Acute Pain
Study type: Interventional
Phase: Phase 2

Summary: 
      This study will evaluate how genetic makeup contributes to the variation in people regarding
      their sensitivity to and experience of pain. Scientists believe that differences in
      information found in genes may explain why an analgesic drug, that is, one that treats pain,
      works effectively for some people but not for others. The study will explore pain that is
      acute (fast and short period). Knowledge gained from this ongoing study may permit
      development of an individualized analgesic drug prescription.

      Patients ages 16 to 35 who are in good health and have been referred for removal of impacted
      wisdom teeth; who are not allergic to aspirin or other nonsteroidal anti-inflammatory drugs
      (known as NSAIDs), sulfites, or certain anesthetics; who are not pregnant or nursing; and who
      are willing to have a biopsy before and after dental surgery are eligible for this study.

      Patients will come to the clinic for one test visit and one treatment visit. During the first
      visit, a questionnaire will evaluate patients' psychological state, including mood and
      depression. There will be a clinical examination of their wisdom teeth. A blood sample of 10
      milliliters (about 0.4 ounces) will be collected from the forearm to provide DNA material
      containing genes stored in cells. The primary genetic analysis will be done at NIH, although
      the DNA collected might also be sent to a laboratory outside NIH. DNA samples will be coded
      so that names of patients cannot be traced.

      During the second visit, two of the patients' lower wisdom teeth will be removed. Patients
      will be given a local anesthetic in the mouth and a sedative given through a vein in the arm.
      While the mouth is numb, a small piece of tissue will be removed from inside the cheek, near
      the wisdom tooth. It is the first biopsy. After the two wisdom teeth are removed, a small
      piece of tubing will be placed into both sides of the mouth where the teeth were removed.
      Every 20 minutes, for the next 3 hours, the researchers will collect inflammatory fluid from
      the tubing, to measure the chemicals thought to cause pain and swelling. Also every 20
      minutes, patients will rate the pain they feel by answering questions. If there is pain
      before 3 hours following surgery, they will receive a dose of fentanyl to relieve moderate to
      severe pain. A second biopsy will occur 3 hours after surgery, to measure changes in
      chemicals produced in response to surgery. Immediately afterward, patients will receive 30 mg
      of ketorolac (Toradol) whether or not pain is felt. They will answer questionnaires about
      pain for 3 hours after receiving the drug, to rate how well it works. They will stay at the
      clinic up to 6 hours after the surgery. If pain is not relieved with ketorolac, patients will
      receive a one-time dose of tramadol, a pain medication for moderate to severe pain. After the
      study procedures are completed, patients will receive pain medication for pain after surgery.

      Patients will be monitored closely, because all drugs have side effects. Ketorolac is a
      nonsteroidal anti-inflammatory drug, one that may cause gastrointestinal upset. Fentanyl is a
      powerful narcotic drug that is safe at the dosage used in this study, but stomach upset,
      dizziness, and breathing trouble may occur. Also, risks from the biopsy include discomfort
      from injecting the numbing medicine, infection, and bleeding. There may be discomfort from
      the sedative injected into the vein, and there may be bruising.

      Benefits from participating are having wisdom teeth removed at no cost as well as close
      monitoring before and after surgery. There are no plans to give patients the results of
      genetic tests or questionnaires. Years of research may be needed before such information has
      the chance to become meaningful.
    

Detailed description: 
      The proposed clinical trial will evaluate the role of genetic factors including single
      nucleotide polymorphisms from cyclooxygenase (COX) - 2 gene on acute pain after tissue injury
      and the analgesic effect of a COX inhibitor. Patients will be healthy volunteers scheduled
      for the surgical removal of impacted third molars. Genotyping will be performed before
      surgery and patients stratified to treatment with a COX inhibitor in this protocol or to
      other protocols examining different polymorphisms.

      Under local anesthesia, 2 mandibular third molars will be removed. Microdialysis sampling in
      the extraction socket will be performed with pre- and post-surgical biopsies. Patients will
      receive a COX inhibitor as an analgesic drug for the post-operative pain. Outcomes evaluated
      will include clinical pain response, gene expression profile using microarray and
      quantitation of related proteins after oral surgery and the interaction of these factors with
      analgesia by a COX inhibitor. By studying these responses in patient samples for each
      genotype (non-variant homozygote, heterozygote and variant homozygote) from the COX-2 gene,
      we will attempt to replicate and extend previous findings on the role of genetic factors in
      the inflammatory process, clinical pain and variation in response to analgesic drugs.
    

Intervention name(s): Valdecoxib; COX Inhibitor
Intervention type(s): Drug; Drug
Intervention MeSH terms: Valdecoxib; Cyclooxygenase Inhibitors
Primary purpose: Treatment
Keywords: Single Nucleotide Polymorphism; Analgesic Efficacy; Oral Surgery Model; Cyclooxygenase Inhibitor; Gene Expression Profile; Wisdom Teeth; Third Molar Extraction