Analgesic Tolerance to Repeated Doses of Subcutaneous Morphine

This study has been completed.
Sponsor:
Information provided by:
University of California, San Francisco
ClinicalTrials.gov Identifier:
NCT00256347
First received: November 16, 2005
Last updated: April 12, 2011
Last verified: March 2011
  Purpose

30 healthy volunteers will be enrolled in this 6-session study. The first visit will be a screening/orientation session. The next 5 visits will be (full day) outpatient sessions taking place Monday through Friday during one week. All full day visits will be drug administration sessions with subjects randomized to one of two groups. The primary purpose is to investigate the time course of development of analgesic tolerance (loss of pain relieving effect) to morphine on experimentally produced skin tenderness in healthy volunteers.


Condition Intervention
Healthy Volunteers
Drug: intramuscular injections of morphine

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double-Blind
Official Title: Development of Analgesic Tolerance to Repeated Doses of Subcutaneous Morphine Using the Brief Thermal Sensitization Model in Healthy Volunteers

Resource links provided by NLM:


Further study details as provided by University of California, San Francisco:

Primary Outcome Measures:
  • To investigate the time course of development of analgesic tolerance (loss of pain relieving effect) to morphine on experimentally produced skin tenderness in healthy volunteers.

Secondary Outcome Measures:
  • To expand the knowledge about the analgesic (pain relieving) effects of opioids on experimentally induced pain and further validate the Brief Thermal Sensitization model as a tool for testing analgesic drugs.

Estimated Enrollment: 30
Study Start Date: March 2005
Study Completion Date: December 2006
Primary Completion Date: December 2006 (Final data collection date for primary outcome measure)
Detailed Description:

30 healthy volunteers will be enrolled in this 6-session study. The first visit will be a screening/orientation session. The next 5 visits will be (full day) outpatient sessions taking place Monday through Friday during one week. All full day visits will be drug administration sessions with subjects randomized to one of two groups. Group A will receive two daily intramuscular injections of 8 mg morphine on Monday through Thursday and two intramuscular injections of placebo on Friday. Group B will receive two daily intramuscular injections of placebo on Monday through Thursday and two intramuscular injections of 8 mg morphine on Friday. During the Monday through Friday sessions the painfulness of experimental heat application and the area of skin tenderness (primary and secondary hyperalgesia) will be assessed before and two times after the intramuscular injections. Heat will be applied by using a computer controlled probe that applies heat (450 C/1130 F) on the thigh for 3 minutes (Brief Thermal Sensitization model.)

  Eligibility

Ages Eligible for Study:   21 Years to 50 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. Healthy volunteers who are 21-50 years of age,
  2. If female, must be non-lactating, not pregnant, and using a reliable contraception method (i.e. abstinence, intrauterine device [IUD], hormonal birth control, or double barrier method [male condom, female condom, or diaphragm plus a spermicidal agent such as contraceptive foam, jelly or cream]).
  3. In stable health
  4. Must weigh between 110 and 200 lbs and have a Body Mass Index between 20 and 30.
  5. Able and willing to provide written informed consent
  6. Able to understand and follow the instructions of the investigator, including the pain intensity rating scales
  7. Develops temporary secondary hyperalgesia from the brief thermal sensitization stimulation procedure performed at the screening visit (Session 1)
  8. Opioid naïve (no previous history of long term opioid use)

Exclusion Criteria:

  1. Severe coronary artery disease, uncontrolled hypertension, cardiac ventricular conduction abnormalities, or orthostatic mean blood pressure drop > than 25 mmHg, severe chronic obstructive pulmonary disease.
  2. History of renal or hepatic failure.
  3. Evidence of hepatic, hematological, or renal dysfunction based on judgment of physician.
  4. Subjects receiving treatment with topical steroids in areas to be stimulated.
  5. Dermatopathology, skin hypersensitivity, or skin lesions in the area of measurements on the thigh and forearm.
  6. Allergy to opioids.
  7. Concomitant treatment with anticonvulsants, antidepressants, NMDA blockers, muscle relaxants, sedatives, other psychotropic drugs or opioids.
  8. Is currently taking or has taken a monamine oxidase inhibitor (MAOI) drug within two weeks prior to study medication sessions.
  9. Use of NSAIDs or acetaminophen within 36 hours of drug treatment sessions and/or use of caffeine or alcohol beginning 24 hours prior to the first drug treatment sessions.
  10. Use of long-acting NSAIDs such as piroxicam or naproxen (Naprosyn) within 1 week of oral drug treatment sessions.
  11. Heat pain detection thresholds above 47°C/116.6°F on the arm (see below).
  12. Subjects who are not within following parameters for weight: between 110 and 200 pounds and between 20 and 30 using the Body Mass Index.
  13. Subjects who are unable to read or speak English.
  14. Diagnosis of insulin-requiring diabetes mellitus.
  15. Current diagnosis of drug or alcohol abuse or history of opioid drug abuse
  16. Use of opioids or alcohol while in study, confirmed by urine drug-screen at Session 1 and Session 2 and breathalyzer for alcohol at Sessions 2-6.
  17. Neurological dysfunction or psychiatric disorder severe enough to interfere with assessment of pain and sensory systems.
  18. Has received an investigational drug within 30 days prior to Study Visit 2 or is scheduled to receive another opioid medication during the course of this study.
  19. Chronic pain condition requiring regular physician visits and prescription medication use on a daily basis.
  20. Subjects who in the opinion of the investigator are considered unable to adhere to scheduled appointments, unlikely to comply with the study protocol, or who are unsuitable for any other reason.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00256347

Locations
United States, California
UCSF
San Francisco, California, United States, 94115
Sponsors and Collaborators
University of California, San Francisco
Investigators
Principal Investigator: Karin Petersen, MD University of California, San Francisco
Principal Investigator: Michael C Rowbotham, MD University of California, San Francisco
  More Information

No publications provided

ClinicalTrials.gov Identifier: NCT00256347     History of Changes
Other Study ID Numbers: H5612-25135, H5612-25135
Study First Received: November 16, 2005
Last Updated: April 12, 2011
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Analgesics
Morphine
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Analgesics, Opioid
Central Nervous System Depressants
Narcotics

ClinicalTrials.gov processed this record on April 14, 2014