Analgesic Tolerance to Repeated Doses of Subcutaneous Morphine

April 12, 2011 updated by: University of California, San Francisco

Development of Analgesic Tolerance to Repeated Doses of Subcutaneous Morphine Using the Brief Thermal Sensitization Model in Healthy Volunteers

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.)

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
30

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • San Francisco, California, United States, 94115
        • UCSF

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

21 years to 50 years (Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Double

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
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

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
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.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University of California, San Francisco

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Karin Petersen, MD, University of California, San Francisco

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
March 1, 2005

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 1, 2006

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 1, 2006

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
November 16, 2005

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 16, 2005

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
November 21, 2005

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
April 14, 2011

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 12, 2011

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2011

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • H5612-25135

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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