Effect of Spinal Ketorolac After Acute Opioid Exposure

This study has been terminated.
(the manufacturing of preservative free ketorolac (Acular-PF) was discontinued)
Sponsor:
Collaborator:
Information provided by (Responsible Party):
James C. Eisenach, M.D., Wake Forest School of Medicine
ClinicalTrials.gov Identifier:
NCT00693160
First received: February 15, 2008
Last updated: March 7, 2014
Last verified: March 2014
  Purpose

This research study is being done because pain is a significant problem for patients with a variety of medical problems and following surgery or traumatic injury. Currently available pain medications may not treat all types of pain or may treat pain only at doses that produce side effects and complications. The medication in this study may have a role in better treatment of pain. The goals of this study are to see if a dose of ketorolac (non-narcotic, pain reliever), given into the fluid in the back near the spine has any effect on pain or discomfort in the skin sensation that will take place after applying capsaicin (chili pepper) cream. The sunburn-like sensation that people experience after having capsaicin cream applied is similar to, but much milder than, the pain that some people have after surgery and after certain types of nerve injuries. This study will test the effects of combining two medications that are often given together to control postoperative pain or pain from a nerve injury. The investigators are especially interested in answering two questions about the effects of ketorolac (non-narcotic pain reliever) and remifentanil (intravenous [IV] narcotic painkiller):

  1. How much does remifentanil (narcotic painkiller) affect the sunburn-like painful area on your skin, which develops after applying capsaicin cream?
  2. What pain relieving effects does spinal ketorolac have when given with IV remifentanil?

Condition Intervention Phase
Healthy
Drug: ketorolac
Drug: placebo
Drug: remifentanil
Drug: Capsaicin
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
Official Title: Effect of Intrathecal Ketorolac on Mechanical Hypersensitivity Following Acute Opioid Exposure

Resource links provided by NLM:


Further study details as provided by Wake Forest School of Medicine:

Primary Outcome Measures:
  • Hyperalgesia [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
    Total Area of hypersensitivity (measured in centimeters) were assessed approximately 24 hours post intrathecal ketorolac injection by the method of using a von Frey filament


Secondary Outcome Measures:
  • Cerebrospinal Fluid (CSF) Prostaglandin E2 (PGE2) Concentration [ Time Frame: 2.5 hours ] [ Designated as safety issue: No ]
    Concentration of prostaglandin E2 (PGE2) in Cerebrospinal fluid (CSF) 2.5 hours post injection of intrathecal ketorolac


Enrollment: 30
Study Start Date: December 2007
Study Completion Date: January 2011
Primary Completion Date: October 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Intrathecal Ketorolac
In the presence of a remifentanil infusion subject will receive a single intrathecal injection of ketorolac 2 mg Each subject will receive the topical capsaicin model for hyperalgesia and allodynia assessment.
Drug: ketorolac
single intrathecal injection of ketorolac 2 mg
Other Names:
  • ketorolac
  • toradol
  • acular pf
Drug: remifentanil
All subjects will receive a remifentanil infusion
Other Name: ultiva
Drug: Capsaicin
Topical capsaicin pain model utilized for each subject
Placebo Comparator: Placebo intrathecal injection
In the presence of remifentanil the subject will receive a single intrathecal injection of placebo (preservative-free normal saline) Each subject will receive the topical capsaicin model for hyperalgesia and allodynia assessment.
Drug: placebo
subject will receive a placebo (preservative free normal saline) spinal injection
Other Name: placebo
Drug: remifentanil
All subjects will receive a remifentanil infusion
Other Name: ultiva
Drug: Capsaicin
Topical capsaicin pain model utilized for each subject

Detailed Description:

Intravenous (IV) remifentanil stimulates spinal COX activity, leading to increased Cerebrospinal fluid CSF) prostaglandin E2 (PGE2) concentrations and areas of capsaicin-induced mechanical hypersensitivity after remifentanil infusion, and these effects will be blocked by intrathecal ketorolac.

Areas of mechanical hyperalgesia and allodynia will be established by topical capsaicin + intermittent heat in healthy volunteers, who will be randomized to receive intrathecal saline or ketorolac during remifentanil infusion, with primary outcome measure area of hyperalgesia and secondary outcome measure Cerebrospinal fluid (CSF) prostaglandin E2 (PGE2) concentration after stopping remifentanil.

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • healthy
  • American Society of Anesthesiologist (ASA) I or II classification
  • between the ages of 18-55
  • weigh less than 250 pounds
  • without chronic pain

Exclusion Criteria:

  • taking analgesics in the last 2 weeks
  • positive urine drug screen
  • pregnancy
  • currently taking any prescription antidepressants or other medications that are mood altering
  • liver or kidney disease
  • stomach ulcers
  • allergies to ketorolac, lidocaine, or capsaicin cream
  • lung disease (COPD)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00693160

Locations
United States, North Carolina
Wake Forest University Health Sciences
Winston-Salem, North Carolina, United States, 27157
Sponsors and Collaborators
Wake Forest School of Medicine
Investigators
Principal Investigator: James C. Eisenach, M.D. Wake Forest School of Medicine
  More Information

No publications provided

Responsible Party: James C. Eisenach, M.D., Professor, Wake Forest School of Medicine
ClinicalTrials.gov Identifier: NCT00693160     History of Changes
Other Study ID Numbers: IRB00002457, GM48085
Study First Received: February 15, 2008
Results First Received: May 15, 2013
Last Updated: March 7, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Wake Forest School of Medicine:
healthy volunteers
analgesia
pain
Healthy subjects

Additional relevant MeSH terms:
Capsaicin
Ketorolac
Ketorolac Tromethamine
Remifentanil
Analgesics, Opioid
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Antipruritics
Dermatologic Agents
Therapeutic Uses
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Anti-Inflammatory Agents
Antirheumatic Agents
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Central Nervous System Agents
Central Nervous System Depressants
Hypnotics and Sedatives
Anesthetics, Intravenous
Anesthetics, General
Anesthetics

ClinicalTrials.gov processed this record on July 20, 2014